breast committee - swog 2001/breast.pdf · tamoxifen alone 15 32 3 91 tamoxifen plus mpa 16 26 10...

APRIL 27 - 29, 2001 SOUTHWEST ONCOLOGY GROUP BREAST 1

BREAST COMMITTEE

Chair: Robert B. Livingston, M.D.Co-Chair: Julie R. Gralow, M.D.

Statisticians: Stephanie J. Green, Ph.D.

Danika Lew, M.A.Sheryl Giarritta, M.S.

Data Coordinators: Diana Lowry, B.A.Karin Rantala, R.H.I.T.Lauren Crowley, B.A.Jean Barce, B.A.Stephanie Edwards

Protocol Coordinator: Tamra N. Oner, B.S.

Pathology: TBARadiation Oncology: Lori J. Pierce, M.D.

Surgery: V. Suzanne Klimberg, M.D.Cancer Control Liaison: Silvana Martino, D.O.

Nurses: Dorothy Coleman, R.N., M.S.N.

Marcia L. Grove-Conrad, R.N.,M.P.H.

Clinical ResearchAssociates:

Deanna Pelensky, C.R.A.Lynn B. Warren, C.R.A.Pamela Williams, R.N., M.S.N.

2 BREAST SOUTHWEST ONCOLOGY GROUP APRIL 27 - 29, 2001

CONTENTS

Breast Committee Agenda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Initial Registrations to Therapeutic Studies . . . . . . . . . . . . . . . . . . . . . 5

Patient Registration by Study and Arm . . . . . . . . . . . . . . . . . . . . . . . 5

E1199 Phase III Intergroup. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

JMA17 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

N9831 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

S9342 Cancer Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

S9623 Phase III Intergroup. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15


S9719 Biologic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

S9832 Phase III. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27


S0012 Phase III. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

S0029 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

S0102 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

S0110 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35


Breast Committee Agenda

Announcements

Scientific Presentation

Active Adjuvant Studies

E1199 AC-Taxol vs AC-Taxotere for Node Positive Breast Cancer Dr. Martino

JMA17 Letrozole vs Placebo After Five Years of Adjuvant Tamoxifen Dr. Martino

N9831 AC-Taxol +/- Herceptin for HER-2 Positive, Three-ArmRandomized Trial in Node Positive Breast Cancer

Dr. Martino

S9927 Post-Mastectomy RT for Patients with 1-3 Positive Nodes Dr. Pierce

Active Cancer Control Studies

S9342 Late Cardiac Effects in Women Treated on S8897 Dr. Ganz

S9630 Trial to Prevent Endometrial Pathology in Women ReceivingTamoxifen

Drs. Potkul and Albain

S9832 Enhancing Well-Being During Breast Cancer Recurrence Dr. Gotay

Proposed Studies

S9905 Zoledronate as Adjuvant Therapy for Primary Breast Cancer Dr. Gralow

S0012 Locally Advanced Disease, AC vs AC+G-CSF Drs. Ellis andLivingston

S0029 Taxotere for Elderly Drs. Martino and Albain

S0102 Metastatic Disease, Her2 Negative, Docetaxel + Vinorelbine Dr. Gralow

S0110 Metastatic Disease, Her2 Positive, Docetaxel + Carboplatin +Herceptin

Drs. Kash and Albain

Adjuvant Trials Dr. Livingston

Closed Studies

C9741 Sequential ATC vs Concurrent AC Followed by T at 14 or 21Day Intervals in Women with Node Positive Stage II/IIIA BreastCancer

Dr. Martino

E2197 AT vs AC in High-Risk Node Negative and 1-3 Positive NodePatients

Dr. Martino

S8814 Phase III Intergroup Adjuvant Study in ER+, Postmenopausal,N+ Patients

Dr. Albain


S8897 Phase III Intergroup Adjuvant Study in N- Patients Dr. Hutchins

S9313 Phase III Intergroup Trial of Sequential vs Combined High DoseAC in High Risk Node Negative Patients

Dr. Haskell

S9445 Prognostic Factor Ancillary to S8814 Dr. Ravdin

S9520 Controlled Phase II Study of Doxorubicin and Paclitaxel asFrontline Chemotherapy for Women with Metastatic BreastCancer

Dr. Ravdin

S9623 ABMT in Patients with ��Axillary Lymph Nodes Drs. Bearman andPeters

S9626 Megestrol Acetate as Treatment for Symptoms of OvarianFailure in Women Treated for Breast Cancer

Dr. Goodwin

S9702 Detection of Malignant Cells in Marrow and PBPC Products ofPatients on S9623

Dr. Shpall

S9719 Incidence of Clonal Hematopoiesis Drs. Stock and Slovak


Initial Registrations to Therapeutic Studiesby 12 month Intervals

BREAST COMMITTEE

0

500

1,000

1,500

2,000

Time of registration

JAN 1996DEC 1996

389

392

291

659

JAN 1997DEC 1997

221

172

169

376

JAN 1998DEC 1998

160

180

180

114

JAN 1999DEC 1999

330

466

657

54

JAN 2000DEC 2000

260

422

456

29

MEMBER AFFILIATES CCOP NON-SWOG

Patient Registration by Study and ArmBREAST COMMITTEE

July-Dec2000

Jan-June2000

July-Dec1999

AllPatients

E1199 Breast, Adj, N+, AC-T (Doc v Pac) *

AC then Paclitaxel 175 q3 wks 82 43 0 125AC then Paclitaxel 80 q wk 82 46 0 128AC then Docetaxel 100 q3 wks 79 45 0 124AC then Docetaxel 35 q wk 74 49 0 123

317 183 0 500 E2197 Breast, Adj, N+/-, A Taxotere v AC *

ADR+Taxotere+Cipro+Decadron 0 44 219 434ADR+Cytoxan+Optional Cipro 0 46 214 435

0 90 433 869 JMA17 Breast, Adj, Letrozole vs Placebo *

Blinded Treatment 164 132 99 451

* For non-SWOG coordinated studies only SWOG registrations are shown.


Patient Registration by Study and ArmBREAST COMMITTEE (Continued)

July-Dec2000

Jan-June2000

July-Dec1999

AllPatients

N9831 Breast, Adj, AC-Paclitaxel +/-Trastuzumab *

AC + Paclitaxel 9 0 0 9AC + Paclitaxel �Trastuzumab 8 0 0 8AC + Paclitaxel + Trastuzumab �� 11 0 0 11

28 0 0 28 S9342 Breast, Cardiac Effects, Ancillary to S8897

5-8 and 10-11yr MUGA Scans 0 5 21 163 S9514 Breast, Adj, Elderly N1, Tam/4HPR *

Blinded Treatment 0 0 6 144 S9623 Breast, Adj, ATC vs. Chemo+AHPCS, Ph III

ADR + Taxol + CTX 8 16 24 302ADR/CTX + Hi Dose Chemo + AHPCS 20 6 12 288

28 22 36 590 S9626 Breast, Placebo vs MA for MenopausalSymptoms

X 0 12 30 93Y 0 15 20 93Z 0 12 26 102

0 39 76 288 S9630 Breast, MPA vs Obs for Prevention ofEndometrial Pathology

Tamoxifen alone 15 32 3 91Tamoxifen plus MPA 16 26 10 95

31 58 13 186 S9719 Breast, Clonal Hematopoiesis Ancillary toS9623

Specimen Submission 5 0 8 26 S9832 Breast, Enhancing Well Being

Intervention 11 21 22 85Control 21 18 16 86

32 39 38 171 S9927 Breast, Adj, Post-Mastectomy RT, Ph III

Observation 2 0 0 2Local-Regional RT 2 0 0 2

4 0 0 4

.

* For non-SWOG coordinated studies only SWOG registrations are shown.


E1199/III

E1199 Phase III Intergroup

Coordinating Group: ECOG

Doxorubicin-Cyclophosphamide Therapy Followed by Paclitaxel or DocetaxelGiven Weekly or Every 3 Weeks in Patients with Axillary Node-Positive or

High Risk Node-Negative Breast Cancer

Intergroup Participants:ECOG, SWOG, CALGB, NCCTG

Study Coordinators:J Sparano (ECOG), S Martino, J Ingle (NCCTG),V Jones (CALGB)

Statisticians:S Green, D Lew

Data Coordinator:D Lowry

Date Activated:12/01/1999

Schema

RANDOMIZE

AC

AC

Docetaxel every three weeksAC

AC

Paclitaxel every three weeks

Weekly Docetaxel

Weekly Paclitaxel

ObjectivesTo determine whether docetaxel improves disease-freesurvival and overall survival when compared topaclitaxel following four cycles of doxorubicin-cyclophosphamide therapy.

To determine whether weekly administration oftaxanes (paclitaxel or docetaxel) for 12 weeksimproves disease-free survival and overall survivalwhen compared with the conventional (every 3 weeks)schedule for four cycles following four cycles of doxo-rubicin-cyclophosphamide therapy.

To compare the toxicity of docetaxel given weekly for12 weeks to that of docetaxel given every 3 weeks forfour cycles.

To compare the toxicity of paclitaxel given weekly for12 weeks to that of paclitaxel given every 3 weeks forfour cycles.

To compare the toxicity of paclitaxel given every 3weeks for four cycles to that of docetaxel given every 3weeks for four cycles.

To compare the toxicity of paclitaxel given weekly for12 weeks to that of docetaxel given weekly for 12weeks.

Patient PopulationPatients must have operable histologically confirmedadenocarcinoma of the female breast, with eitherhistologically involved lymph nodes (T1-3, N1-2, M0,Stage II-IIIA) or high risk axillary node-negativedisease (T2N0, stage IIA; T3N0, stage IIB). Patientswho have positive axillary lymph node metastasisshould have at least six axillary lymph nodes removedat axillary dissection. Patients who have had less thansix lymph nodes removed are eligible if the lymphnodes were obtained by a sentinel node biopsy pro-cedure and were negative for metastasis. Patients withbilateral disease are eligible if axillary dissection


E1199/III

revealed positive lymph nodes for at least one of theprimaries.

Randomization must be performed within 84 days ofmastectomy, or within 84 days of axillary dissection ifthe patient’s most extensive breast surgery was a breastsparing procedure. Margins must be clear. No priorchemotherapy or radiation therapy for this malignancyis allowed. Patients may have received tamoxifen forpurposes of prevention or up to four weeks oftamoxifen therapy for this malignancy.

Patients must have adequate hematologic, hepatic, andrenal function. Patients must have no prior history ofcardiac disease. Patients must be at least 18 years old.

Investigators are encouraged to enroll patients withHER2 overexpressing tumors on trial N9831 instead ofthis trial.

Stratification/Descriptive FactorsPatients will be stratified by (1) HER2/neu: negative vspositive vs unknown; (2) age: < 50 vs �� status: positive vs negative vs unknown; (4) nodalstatus: 1-3 vs 4-9 vs 10+; (5) tumor size: ��vs > 5cm vs unknown; (6) current bisphosphonates: yes vs

no; and (7) surgery: mastectomy vs breast conservationtherapy.

Accrual GoalsPlanned accrual for this study is 5000 patients.

Summary StatementThis study was activated in ECOG on October 13,1999, and in SWOG on December 31, 1999. As ofDecember 31, 2000, there were 2138 patients reg-is-tered to this study, 500 of them from SWOG.

According to the November 2000 ECOG report, 283patients have been evaluated for toxicity. One patientrandomized to the AC followed by weekly paclitaxelarm died after being taken to surgery for an exploratorylaparotomy where she was found to have an ischemicgangrenous small bowel. The patient had profoundmetabolic and respiratory acidosis and overwhelmingsepsis, a toxicity possibly related to treatment. Grade 3or 4 non-hematologic toxicities were experienced by32% of the patients evaluated for toxicity on the ACfollowed by paclitaxel every three weeks arm, 27% onthe AC followed by weekly paclitaxel arm, 39% on theAC followed by docetaxel every three weeks arm and33% on the AC followed by weekly docetaxel arm.

Registration by Institution

Registrations ending December 31, 2000

InstitutionsTotalReg Institutions

TotalReg

So Calif, U of 25 Greater Phoenix CCOP 7Loyola University 21 Madigan Army Med Ctr/Puget Sound 7Upstate Carolina 20 Scott & White CCOP 7LSU-Shreveport 17 Columbia River CCOP 6Kansas City CCOP 15 Columbia University 6Central IL CCOP 14 Huntington Mem Hosp/So Calif, U of 6Dayton CCOP 14 Montana CCOP 6Puget Sound 14 St Francis/Stormont/Kansas, U of 6Atlanta Reg CCOP 13 Central Baptist Hosp/Cincinnati MC, U of 5Utah, U of 11 Nevada Cancer Center/So Calif, U of 5Mansfield Gen Hosp/Cleveland Clinic OH 10 Santa Rosa CCOP 5St Louis CCOP 10 Schumpert Med Ctr/San Antonio, U of TX 5U of Tennessee MC/San Antonio, U of TX 10 Sierra Nevada Mem/Davis, U of CA 5Fairview Health Sys/Cleveland Clinic OH 9 St Anthony Hospital/Colorado, U of 5Doctors Medical Ctr/Davis, U of CA 8 St Mary’s Hosp/St Louis University 5Exempla Lutheran MC/Colorado, U of 8 Sutter Hlth Western/Davis, U of CA 5Grand Rapids CCOP 8 William Beau Hosp/Michigan, U of 5Hawaii CCOP, Univ of 8 All Other Institutions 153S Georgia Med Ctr/BAMC/WHMC 8 Total (103 Institutions) 500Washington Reg MC/Arkansas, U of 8


JMA17/III

JMA17 Phase III Intergroup

Coordinating Group: NCIC

A Phase III Randomized Double Blind Study of Letrozole Versus Placebo inWomen with Primary Breast Cancer Completing Five or More Years of

Adjuvant Tamoxifen

Intergroup Participants:NCIC, SWOG, CALGB, ECOG, EORTC, IBCSG, NCCTG

Study Coordinators:P Goss (NCIC), S Martino, N Robert (ECOG),H Muss (CALGB), M Castiglione (IBCSG),M Piccart (EORTC), E Perez (NCCTG)


Data Coordinator:K Rantala


Schema

R

A

N

D

O

M

I

Z

E

Letrozole x 5 years

Placebo x 5 years

4 1/2 - 6 years

Adjuvant Tamoxifen

ObjectivesTo determine the disease-free survival and overallsurvival for women who have previously received atleast five years of adjuvant tamoxifen, randomized toreceive either letrozole 2.5 mg daily or placebo dailyfor five years.

To evaluate the incidence of contralateral breastcancer.

To evaluate the long term clinical and laboratory safetyof letrozole with special attention on lipid profile asassessed by blood sampling, cardiovascular morbidityand mortality, the incidence of all bone fractures,changes in bone density, and common toxicities.

To evaluate overall quality of life.

Patient PopulationPatients must have had histologically or cytologicallyconfirmed breast carcinoma that was surgicallyremoved at the time of original diagnosis, with noevidence of metastasis. The primary tumor must nothave been receptor negative (i.e., both ER and PgR

negative). There must be no evidence of breast cancerrecurrence at randomization.

Patients must have completed at least 4 1/2 years butnot more than six years of adjuvant tamoxifen.Randomization must be within three months oftamoxifen discontinuation. Patients may have receivedprior adjuvant chemotherapy or radiation therapy at thetime of original diagnosis.

Patients must be post-menopausal and have an ECOGperformance status of 0-2. Patients must have adequatehematologic and hepatic function. Patients must not beregistered to any other adjuvant breast cancer trial.

Stratification/Descriptive FactorsPatients will be stratified by (1) receptor status atdiagnosis: positive vs unknown; (2) lymph node statusat diagnosis: negative vs positive vs unknown; and (3)prior adjuvant chemotherapy: yes vs no.


JMA17/III

Cancer Control CreditsThe NCI Division of Cancer Prevention (DCP) hasassigned 0.5 cancer control credits per registration forthis study.

Accrual GoalsPlanned accrual for this study is 2380.

Summary StatementThis study was activated in the NCIC on August 24,1998. As of December 31, 2000, there had been 2139registrations, 451 of them from SWOG.

According to a February 2000 NCIC report, forpatients with information available at baseline, 31%were age 70 or over, 57% received 5-6 years oftamoxifen, 8% were T3-4 at diagnosis, 45% were node

positive at diagnosis, 49% were node negative atdiagnosis, 6% had unknown axillary node status, 96%were receptor positive, 4% had unknown receptorstatus, 9% had osteoporosis, and 15% had cardio-vascu-lar disease.

The most frequently reported toxicities were edema,hot flashes, fatigue, sweating, nausea, dizziness, andheadache. The only Grade 4 toxicity reported was onecase of dizziness.

Only four patients had been found ineligible: one pre-menopausal, one with prior recurrence, and two withamount of prior tamoxifen out of the required range.

An increase in sample size is under discussion.




TotalReg

Central IL CCOP 29 Loyola University 7Northwest Med Ctr/Arkansas, U of 20 St Louis CCOP 7Greenville CCOP 18 Wayne State Univ 7Southeast CCC CCOP 18 Cleveland Clinic OH 6Puget Sound 15 Eisenhower Army MC/BAMC/WHMC 6Scott & White CCOP 15 Santa Rosa CCOP 6So Calif, U of 14 Sutter Hlth Western/Davis, U of CA 6LSU-Shreveport 13 Central Baptist Hosp/Cincinnati MC, U of 5BAMC/WHMC 12 St Joseph Med Ctr/Boston Univ Med Ctr 5Grand Rapids CCOP 12 West Florida Med Ctr/Arkansas, U of 5Ozarks Reg CCOP 12 Arizona, U of 4St Lukes/Mt States/Utah, U of 12 Henry Ford Hosp 4Northwest CCOP 11 John Muir Med Ctr/Davis, U of CA 4Our Lady, Bellefonte/Cleveland Clinic OH 11 MD Anderson, Florida/Arkansas, U of 4Utah, U of 9 Montana CCOP 4Columbus CCOP 8 Mt Clemens Gen Hosp/Wayne State Univ 4Madigan Army Med Ctr/Puget Sound 8 San Antonio, U of TX 4Michigan, U of 8 Wichita CCOP 4Upstate Carolina 8 Wooster Clinic/Cleveland Clinic OH 4Virginia Mason CCOP 8 Yakima Valley Mem/Puget Sound 4Columbia River CCOP 7 All Other Institutions 76Dayton CCOP 7 Total (83 Institutions) 451


N9831/III

N9831 Phase III Intergroup

Coordinating Group: NCCTG

Phase III Trial of Doxorubicin and Cyclophosphamide (AC) Followed byWeekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for

Women With HER-2 Overexpressing Node Positive Breast Cancer

Intergroup Participants:NCCTG, SWOG, ECOG

Study Coordinators:E Perez (NCCTG), S Martino, N Davidson (ECOG)


Data Coordinator:D Lowry


Schema

RANDOMIZE

AC

AC

AC

Paclitaxel

Paclitaxel

Paclitaxel + Trastuzumab

Trastuzumab

Trastuzumab

ObjectivesTo compare the combination AC followed by weeklypaclitaxel with the sequential schedule of the comb-ination of AC, weekly paclitaxel, and trastuzumab interms of disease-free survival (DFS) and overall sur-vival (OS).

To compare the combination of AC followed byweekly paclitaxel with the combination AC followedby the combination of weekly paclitaxel and trastuzu-mab in terms of DFS and OS.

To compare the sequential schedule of the combinationAC, weekly paclitaxel, and trastuzumab with thecombination of AC followed by the combination ofweekly paclitaxel and trastuzumab in terms of DFS andOS.

To compare the cardiotoxicities of (1) AC followed byweekly paclitaxel, (2) AC followed by weeklypaclitaxel followed by weekly trastuzumab, and (3) ACfollowed by weekly paclitaxel and trastuzumabfollowed by weekly trastuzumab.

To determine whether higher levels of shed ECD(extracellular domain) or autoantibodies to HER-2 andHER-1 measured in the serum prior to treatment areprognostic for DFS and OS.

To determine the concordance of HER-2 over-expression as measured by HerceptTest (DAKO) andVysis FISH; and to estimate the degree to which over-expression, as measured by each of these assays, isassociated with DFS and OS.

Patient PopulationPatients must have operable, histologically confirmedadenocarcinoma of the female breast and positivelymph nodes (T1-3, pN1-2, M0) with no dermallymphatic involvement. Node positivity may bedetermined by either an axillary node dissection or apositive sentinel node finding by immunohisto-chemistry. cN2 disease is not eligible. Patients musthave ER and PgR determination. Patients must stronglyexpress HER-2/neu as defined in the protocol.

Randomization must be performed within 84 days ofmastectomy, or within 84 days of axillary dissection if


N9831/III

the patient’s most extensive breast surgery was a breastsparing procedure. Margins must be clear. No priorchemotherapy, radiation therapy, immunotherapy, orbiotherapy for breast cancer is allowed. No prioranthracycline or taxane for any malignancy is allowed.Patients may have received tamoxifen or raloxifene forpurposes of chemoprevention or up to four weeks oftamoxifen therapy for this malignancy.

Patients must have adequate hematologic and hepaticfunction. Patients must have no active cardiac disease,and LVEF must be within normal range. Patients mustbe at least 18 years old.

Stratification/Descriptive FactorsPatients will be stratified by (1) positive nodes: axillarydissection with 1-3 nodes vs axillary dissection with

4-9 nodes vs axillary dissection with 10+ nodes vspositive sentinel node with no axillary dissectionperformed; and (2) receptor status: ER positive or PgRpositive vs other.

Accrual GoalsThe accrual goal for this study is 3000 eligible patients,1000 in each arm. Three formal interim analyses areplanned, when approximately 50%, 67%, and 75% ofthe total events have occurred.

Summary StatementThis study was activated by NCCTG on May 19, 2000,and in SWOG on July 1, 2000. As of December 31,2000, there were 104 patients registered to this study,28 of them from SWOG.




TotalReg

Good Samaritan HS/Kansas, U of 3 Mobile Infirmary MC/Tulane University 1Loyola University 3 Northwest CCOP 1Salem Hospital/Oregon Hlth Sci Univ 3 Salina Reg Hlth Ctr/Kansas, U of 1Southeast CCC CCOP 3 South Texas Onc/Hem/San Antonio, U of TX 1St Joseph Med Ctr/Boston Univ Med Ctr 2 St Bernards Reg MC/Arkansas, U of 1St Lukes/Mt States/Utah, U of 2 Thompson Ca Surv Ctr/San Antonio, U of TX 1Davis, U of CA 1 Valley Hospital/Columbia University 1Hawaii CCOP, Univ of 1 Yakima Valley Mem/Puget Sound 1Hendrick Cancer Ctr/San Antonio, U of TX 1 Total (18 Institutions) 28Kansas City CCOP 1


S9342

S9342 Cancer Control

A Study of the Late Cardiac Effects of Two Different Adjuvant ChemotherapyRegimens in Women with Node Negative Breast Cancer Treated on S8897

Study Coordinators:P Ganz, K Albain, L Hutchins

Statisticians:S Green, S Giarritta

Data Coordinators:D Lowry, L Crowley


ObjectivesTo compare the frequency of sub-clinical congestiveheart failure in women treated with CMF or CAFchemotherapy in S8897 as measured by resting MUGAscan at 5-8 and 10-11 years after randomization.

To estimate the frequency of late cardiac effects(congestive heart failure, cardiac ischemic events,clinical symptoms) in women treated with CMF orCAF chemotherapy on S8897.

To prospectively monitor annual cardiac eventsbetween the 5th and 10th year after randomization.

Patient PopulationPatients must be registered to Arms I-IV of S8897 andhave completed at least one course of the assignedchemotherapy. Registration to S9342 must occurbetween five years three months and eight years postS8897 randomization or between 10 and 11 years postrandomization. A MUGA must have been obtainedwithin three months prior to registration, or must beplanned within one month after registration.

Pregnant or nursing women must agree not to have anuclear medicine study, but may otherwise participate.Women of reproductive potential may not participateunless they have agreed to use an effective contra-ceptive method during and for one month after the

MUGA scan. Patients must be disease-free, without apast recurrence.


Accrual GoalsThe accrual goal is at least 70 patients per treatmentgroup registered in years 5-8 and an additional 25patients per group registered in years 10-11.

Summary StatementAs of December 31, 2000, 163 patients had been reg-istered to this study, 80 from CMF arms and 83 fromCAF arms. No more patients are available in the 5-8years post randomization group.

The study was amended on March 1, 2001 to allowregistration of patients between 10 and 11 years postrandomization on S8897.

Funding is still available for reimbursement of allMUGA scans for patients registered to this study.

The annual cardiac history form submission rates forpatients qualifying for assessments are as follows:5-year assessment, 99%; 6-year assessment, 93%;7-year assessment, 92%; 8-year assessment, 76%; and9-year assessment, 57%.


S9342

Initial Registrations By 3 Month Intervals

0

10

20

30

40

Time of Registration

JANMAR1997

1APRJUN1997

8

JULSEP1997

10

OCTDEC1997

19

JANMAR1998

6

APRJUN1998

19

JULSEP1998

22

OCTDEC1998

31

JANMAR1999

16

APRJUN1999

5

JULSEP1999

13

OCTDEC1999

8

JANMAR2000

4

APRJUN2000

1

Total




TotalReg

Wichita CCOP 20 Virginia Mason CCOP 4Greenville CCOP 12 Arizona, U of 3Ozarks Reg CCOP 10 Columbus CCOP 3Kansas City CCOP 8 Irvine, U of CA 3Arkansas, U of 6 Northwest CCOP 3Henry Ford Hosp 6 San Antonio, U of TX 3Oregon Hlth Sci Univ 6 South Alabama CCOP 3Salina Reg Hlth Ctr/Kansas, U of 6 St Francis/Stormont/Kansas, U of 3So Calif, U of 6 Dixie Medical Center/Utah, U of 2LSU-Shreveport 5 East Texas Med Ctr/San Antonio, U of TX 2St Edward Mercy MC/Arkansas, U of 5 Michigan, U of 2Dayton CCOP 4 Muskogee Reg Med Ctr/Oklahoma, Univ of 2Grand Rapids CCOP 4 Providence Hospital/Cleveland Clinic OH 2Harrington/TexasTech/San Antonio, U of TX 4 All Other Institutions 18Loyola University 4 Total (47 Institutions) 163Sutter Hlth CRG-East/Davis, U of CA 4


S9623/III

S9623 Phase III Intergroup

Coordinating Group: SWOG

A Comparison of Intensive Sequential Chemotherapy Using Doxorubicin PlusPaclitaxel Plus Cyclophosphamide with High Dose Chemotherapy and

Autologous Hematopoietic Progenitor Cell Support for Primary Breast Cancerin Women with ��Axillary Lymph Nodes

Intergroup Participants:SWOG, CALGB, ECOG, MDACC, NCCTG

Study Coordinators:S Bearman, L Pierce, W Peters, J Ingle (NCCTG),K Holland (ECOG), C Hudis (CALGB),Z Rahman (MDACC)


Data Coordinators:K Rantala, L Crowley


Date Closed:02/15/2001

Schema

Doxorubicin Paclitaxel Cyclophosphamide Tamoxifen*

RANDOMIZE Induction AC

High Dose Chemotherapy withautologous hematopoietic support Tamoxifen*

* Except premenopausal receptor negative patients

ObjectivesTo compare induction chemotherapy with doxorubicinand cyclophosphamide, followed by high dose chemo-therapy and autologous hematopoietic progenitor cellsupport vs intensive sequential chemotherapy usingdoxorubicin, paclitaxel and cyclophosphamide withG-CSF support with respect to disease-free survivaland overall survival in operable breast cancer patientswith ��

To compare toxicity for patients treated with high-dosechemotherapy with toxicity for patients treated withintensive sequential chemotherapy.

To quantitate the breast cancer cell content of theperipheral blood progenitor cell (PBPC) fractions frompatients randomized to the PBPC-supported arm, usingimmunocytochemistry with anti-breast cancer mono-

clonal antibodies, and reverse transcriptase polymerasechain reaction (RT-PCR) for mucin-1; to correlate theassay results with clinical outcome of the patients(disease-free survival, survival, and pattern of relapse).

Patient PopulationThis study is open to patients with histologicallyconfirmed adenocarcinoma of the female breast with�� histologically confirmed involved axillary lymphnodes. Patients must not have N3, T4, or M1 disease.Patients must have undergone a breast-sparingprocedure or mastectomy with at least 10 nodessampled within 12 weeks prior to registration. Surgicalmargins must be negative for invasive and non-invasive ductal carcinoma.


S9623/III

Patients must have received no prior chemotherapy forany malignancy, and no prior radiotherapy to thebreast.

Patients must have adequate hematologic, renal,hepatic, pulmonary, and cardiac function, and must beHIV negative. Patients must have a SWOG perform-ance status of 0-1 and must not have any seriousmedical or psychiatric illness. All patients must havebeen evaluated and approved for this study, prior toregistration, by a transplant center approved for thisstudy by one of the participating cooperative groups.

Stratification/Descriptive FactorsPatients will be stratified by primary treatment:mastectomy with no RT vs mastectomy + RTfollowing chemotherapy vs breast sparing procedure +RT following chemotherapy. Patients will be describedby (1) menopausal status: pre vs post vs other;(2) estrogen receptor status: ER positive vs ERnegative vs unknown; (3) progesterone receptor status:PgR positive vs PgR negative vs unknown; (4) N2disease: yes vs no; (5) T3 disease: yes vs no; (6)transplant regimen: STAMP I vs STAMP V; and (7)source of progenitor cells: marrow vs peripheral bloodvs both.

Accrual GoalsThe accrual goal is 1000 eligible patients. Two interimanalyses will be performed, after approximately one-third and two-thirds of the expected number of eventshave occurred.

Summary StatementThis study was activated on July 1, 1996. As ofDecember 31, 2000, 590 patients had been enrolled, 28in the last six months. One hundred ten patients arecurrently ineligible, 85 due to missing baseline data.Sixty-six of these could become eligible; institutionsare reminded to submit overdue data. The mostcommon other reasons for ineligibility were positivemargins (6 patients), insufficient number of nodessampled (5), and transplant center not approved bySWOG (3). Major deviations are recorded for onepatient randomized to the sequential chemotherapy arm

who refused the assigned treatment in favor of a trans-plant, and one patient on the transplant arm whoreceived a standard preparatory regimen other thanStamp I or V.

There have been four treatment related deaths,including one probable cardiac death on the sequentialchemotherapy arm (53-year-old patient died suddenlyat home). Three patients on the high dose chemo-therapy arm have died due to toxicity. One patient diedduring induction due to ARDS and infection. Twopatients died due to transplant toxicities: one due tocomplications from VOD, and the other due topneumonia ("Respiratory infection w/o neutropenia").

One hundred thirty-seven out of 231 patients evaluatedfor toxicity on the sequential chemotherapy arm(including 25 patients currently ineligible due to over-due data) experienced Grade 4 toxicities as maximumdegree. Eighteen experienced Grade 4 non-hematologictoxicity, the most common being myalgia/arthralgia infour. The patient who refused the assigned treatment onthe sequential chemotherapy arm in favor of a trans-plant is not assessable for toxicity.

Two hundred sixteen patients were evaluated fortoxicity due to induction on the high dose chemo-therapy arm (including 20 patients currently ineligibledue to overdue data); 135 experienced Grade 4toxicities as maximum degree. Fifteen of theseexperienced non-hematologic Grade 4 toxicities. TheGrade 4 "Cardiovascular - other" toxicity was cardiacarrest and the Grade 4 "GU - other" was renal tubulardamage.

One hundred sixty-five of the 190 patients evaluatedfor toxicity post-transplant experienced Grade 4toxicities as maximum degree. Nineteen of thesepatients experienced non-hematologic Grade 4toxicities. The Grade 4 "GU - other" toxicity washemolytic uremic syndrome and the Grade 4 "Liver -other" was cholecystitis.

The study was closed due to poor accrual on February15, 2001.


S9623/III




TotalReg

CALGB 171 Puget Sound 5ECOG 138 Atlanta Reg CCOP 4NCCTG 21 Harris Methodist/San Antonio, U of TX 4Columbia River CCOP 18 Henry Ford Hosp 4Colorado, U of 16 Ozarks Reg CCOP 4Columbia University 16 Virginia Mason CCOP 4Kaiser Foundatn Hosp/Davis, U of CA 12 Arkansas, U of 3Cincinnati MC, U of 11 Boston Univ Med Ctr 3Cleveland Clinic OH 11 Carilion Medical Ctr/Temple University 3Hawaii CCOP, Univ of 9 Davis, U of CA 3Northwest CCOP 9 Oklahoma, Univ of 3Sutter Hlth CRG-East/Davis, U of CA 9 Salem Hospital/Oregon Hlth Sci Univ 3Sutter Hlth Western/Davis, U of CA 9 San Antonio, U of TX 3BAMC/WHMC 8 St Francis/Stormont/Kansas, U of 3LSU-Shreveport 8 Central IL CCOP 2City of Hope Med Ctr 7 MDACC 2Greater Phoenix CCOP 7 Michigan, U of 2Arizona, U of 6 Poudre Valley Hosp/Colorado, U of 2Dayton CCOP 6 Providence Hosp 2John Muir Med Ctr/Davis, U of CA 5 Salina Reg Hlth Ctr/Kansas, U of 2Loyola University 5 All Other Institutions 22Oregon Hlth Sci Univ 5 Total (64 Institutions) 590

Registration, Eligibility, and Evaluability

Registrations ending December 31, 2000; Data as of February 9, 2001

TOTALADR+TAXOL+

CTX

ADR/CTX+HI DOSE

CHEMO+AHPCS NUMBER REGISTERED 590 302 288

INELIGIBLE 110 60 50Insufficient Documentation 85 42 43

Irreversible 19 8 11Reversible 66 34 32

ELIG./ PEND. ELIG. 480 242 238Analyzable, Pend. Elig. 35 14 21

TOXICITY ASSESSMENTEvaluable 402 206 196Not Evaluable 1 1 0Too Early 77 35 42


S9623/III

Patient Characteristics


ADR+TAXOL+CTX(n=242)

ADR/CTX+HI DOSE

CHEMO+AHPCS(n=238)

AGE

Median 46 .0 45 .0Minimum 25 25Maximum 67 63

RACE

White (Non-Hispanic) 205 85% 217 91%Black (Non-Hispanic) 17 7% 14 6%Hispanic 8 3% 3 1%Asian or Pacific Islander 8 3% 3 1%American Indian 1 0% 1 0%Other 3 1% 0 0%

PRIMARY TREATMENT

Mastectomy, no RT 69 29% 70 29%Mastectomy, RT following chemo 108 45% 103 43%BSP, RT following chemo 65 27% 65 27%

MENOPAUSAL STATUS

Pre 156 64% 166 70%Post 63 26% 55 23%Other 23 10% 17 7%

N2 DISEASE

Yes 24 10% 27 11%No 218 90% 211 89%

T3 DISEASE

Yes 42 17% 48 20%No 200 83% 190 80%

TRANSPLANT REGIMEN

Stamp I 30 12% 34 14%Stamp V 212 88% 204 86%


S9623/III

Number of Patients with a Given Type and Degree of Toxicity

All eligible and selected ineligible patients includedToxicities with No Entries for Grades 4 to 5 Have Been Suppressed


ADR+TAXOL+CTX

ADR/CTX+HI DOSE

CHEMO+AHPCSInduction

(n=231) (n=216)

Grade GradeTOXICITY �� 4 5 �� 4 5

ARDS 231 0 0 215 0 1Anemia 214 17 0 214 2 0Cardiovascular-other 230 0 1 215 1 0Dizziness/light headedness 230 1 0 216 0 0Dizziness/vertigo, NOS 229 2 0 216 0 0Dyspnea 230 1 0 214 2 0Fatigue/malaise/lethargy 230 1 0 216 0 0Febrile neutropenia 229 2 0 215 1 0GU-other 231 0 0 215 1 0Infection w/o 3-4 neutropenia 231 0 0 214 2 0Infection with 3-4 neutropenia 231 0 0 214 1 1Infection, unk ANC 230 1 0 216 0 0LVEF decrease/CHF 231 0 0 215 1 0Leukopenia 113 118 0 143 73 0Myalgia/arthralgia, NOS 227 4 0 216 0 0Neutropenia/granulocytopenia 119 112 0 95 121 0Platelet transfusion 231 0 0 215 1 0Pulmonary edema 231 0 0 215 1 0Respiratory infect w/ neutrop 231 0 0 215 1 0Stomatitis/pharyngitis 228 3 0 213 3 0Thrombocytopenia 225 6 0 213 3 0Thrombosis/embolism 230 1 0 215 1 0Vomiting 228 3 0 211 5 0 MAXIMUM GRADE ANY TOXICITYNumber 93 137 1 80 135 1


S9623/III


TransplantAll eligible and selected ineligible patients included

Toxicities with No Entries for Grades 4 to 5 Have Been SuppressedRegistrations ending December 31, 2000; Data as of February 9, 2001

Total Total(n=190) (n=190)

Grade GradeTOXICITY �� 4 5 TOXICITY �� 4 5

ARDS 189 1 0

Liver-other 189 1 0

Anemia 188 2 0 Mood/consciousness change, NOS 189 1 0Anorexia 184 6 0 Neutropenia/granulocytopenia 55 135 0Confusion 189 1 0 Platelet transfusion 189 1 0Diarrhea without colostomy 189 1 0 Renal failure 188 2 0Esophagitis/dysphagia 188 2 0 Respiratory infect w/o neutrop 189 0 1Febrile neutropenia 188 2 0 SGOT (AST) increase 189 1 0Fever without neutropenia 189 1 0 Second primary 189 1 0Fever, NOS 189 1 0 Stomatitis/pharyngitis 185 5 0GU-other 189 1 0 Supraventricular arrhythmia 189 1 0Hyperglycemia 189 1 0 Thrombocytopenia 133 57 0Hypertension 189 1 0 Thrombosis/embolism 189 1 0Hypocalcemia 189 1 0 Thrombotic microangiopathy 189 1 0Hypokalemia 189 1 0 Veno-occlusive disease 189 0 1Hypotension 189 1 0 Ventricular arrhythmia 189 1 0Infection w/o 3-4 neutropenia 189 0 1Infection with 3-4 neutropenia 189 0 1 MAXIMUM GRADELVEF decrease/CHF 189 1 0 ANY TOXICITYLeukopenia 28 162 0 Number 23 165 2


S9630/III



A Randomized Comparison of Medroxyprogesterone Acetate and Observationfor Prevention of Endometrial Pathology in Postmenopausal Breast Cancer

Patients Treated with Tamoxifen

Intergroup Participants:SWOG, CALGB

Study Coordinators:R Potkul, K Albain, C Salomon, S Wilczynski,S Khan (CALGB)

Statisticians:D Pauler, S Giarritta



Schema

RANDOMIZE Tamoxifen plus Medroxyprogesterone Acetate x 5 years

Tamoxifen alone x 5 years

StartTamoxifen*

*Randomization must occur within 28 days.

ObjectivesPrimary Objectives

To compare endometrial pathologic diagnoses (inparticular, proliferative changes, simple or cystichyperplasia, complex [adenomatous] hyperplasia,hyperplasia with atypia and carcinoma) for post-menopausal, tamoxifen-treated breast carcinomapatients, randomly assigned to tamoxifen alone ortamoxifen plus cyclical medroxyprogesterone acetate.

To compare endometrial pathologic diagnoses resultingin tamoxifen discontinuation (persistent endometrialhyperplasia, atypia or carcinoma) and intermittentbleeding in breast carcinoma patients described above.

Secondary Objectives

To characterize the incidence of spontaneousregression and progression of simple or cystichyperplasia.

To compare changes over time in endometrialoncogene expression and receptor status for thepatients described above.

To describe associations among changes in geneexpression, receptor status, endometrial abnormality,length of tamoxifen exposure, and prior chemotherapyin the patients described above.

To determine the feasibility of collecting centrallyfrozen tissue hysterectomy specimens from tamoxifen-treated breast carcinoma patients for the purpose ofanalyzing the regulation of 17 Beta-hydroxysteroiddehydrogenase activity in endometrial tissue.


S9630/III

To establish a repository of paraffin blocks and frozenendometrial tissue from tamoxifen-treated breastcancer patients.

Patient PopulationPatients must have been diagnosed with primaryinvasive adenocarcinoma of the breast staged as T1-3,N0-1, and M0. Patients must not have sarcoma,lymphoma, or apocrine, adenocystic or squamous cellcancer of the breast. Patients must not have hadrecurrent invasive breast cancer and must be currentlyfree of breast cancer (no evidence of disease). Patientsmust have had definitive local treatment of the primarylesion (mastectomy or breast-sparing procedure) andhave undergone either an axillary node dissection orsampling or a sentinal node biopsy.

Adjuvant chemotherapy is permitted. The therapy mayhave been completed, may be ongoing, or may beplanned to start with the tamoxifen. Patients must nothave received any hormonal treatment, other thantamoxifen per protocol for their breast cancer. Patientsmust be planning to start five years of adjuvanttamoxifen or must have started tamoxifen �� !� � "�prior to registration and be planning to receive adjuvanttamoxifen for five years. Any post-menopausal estro-gen therapy must be discontinued prior to registration.

Patients who are currently eligible for or who weretreated on any adjuvant intergroup trial are not eligiblefor this study. Patients must be female and post-menopausal as defined in the protocol. Patients whohave undergone a hysterectomy are ineligible. Patientswith endometrial hyperplasia, proliferative changes,atypical hyperplasia, or carcinoma as determined byendometrial biopsy are ineligible.

Stratification/Descriptive FactorsPatients are stratified by: (1) prior adjuvant chemo-therapy: yes vs no; and (2) number of positive nodes:0-3 vs > 3.


Accrual GoalsThe accrual goal is 208 patients.

Summary StatementAs of December 31, 2000, 186 patients had beenrandomized. Twenty-five patients are currently in-eligible, 19 due to insufficient documentation. Fourteenof these patients could become eligible with thesubmission of the required documentation. Majordeviations are recorded for one patient who had a totalhysterectomy after randomization, four patients whoincorrectly were given Megace instead of medroxypro-gesterone acetate, and three patients randomized to thetamoxifen plus cyclical medroxyprogesterone acetatearm who did not take any study drug.

Eighty patients have been evaluated for toxicities. Fourof the 42 patients evaluated for toxicity on thetamoxifen plus cyclical medroxyprogesterone acetatearm experienced a Grade 3 toxicity: masculinization,weight gain, respiratory infection and chest tightness.One patient randomized to the tamoxifen only arm diedfrom a myocardial infarction judged to be related totreatment. Common toxicities have been hot flashes,fatigue and edema.

There were four major changes made to the protocol inSeptember 1998 (Amendment #1): (1) endometrialbiopsies (EMB) are required only in cases where anendovaginal sonogram (EVS) shows an endometrialstripe �� EVS(EMB) testing is now requiredonly at pre-study, 2 years, and 5 years, rather thanannually; (3) specific requirements for ER/PgR statushave been removed; and (4) the sample size has beenreduced by 50% because the two study arms will nolonger be compared separately within subsets ofpatients with and without prior chemotherapy.

In July 1999 the study was revised to allow patientswith DCIS, LCIS with microinvasion, or Paget’sdisease to be eligible.

This study was further revised, effective July 1, 2000,to include CALGB as a participant.


S9630/III

Initial Registrations By 6 Month Intervals

0

10

20

30

40

50

60

Time of Registration

JAN 1997JUN 1997

3

JUL 1997DEC 1997

9

JAN 1998JUN 1998

22

JUL 1998DEC 1998

23

JAN 1999JUN 1999

27

JUL 1999DEC 1999

13

JAN 2000JUN 2000

58

JUL 2000DEC 2000

31

Total




TotalReg

Loyola University 30 Wichita CCOP 4Scott & White CCOP 15 Covenant Health Sys/San Antonio, U of TX 3Central IL CCOP 12 Grand Rapids CCOP 3St Francis/Stormont/Kansas, U of 9 Montana CCOP 3Virginia Mason CCOP 9 So Calif, U of 3Columbus CCOP 8 Cancer Care NW/Puget Sound 2Northridge Hosp/Los Angeles, U of CA 7 Henrico Doctors Hosp/Galveston, U of TX 2Sierra Nevada Mem/Davis, U of CA 7 Irvine, U of CA 2Cottage Health Sys/Los Angeles, U of CA 6 Merle West Med Ctr/Davis, U of CA 2Kansas City CCOP 6 N Colorado Med Ctr/Colorado, U of 2BAMC/WHMC 5 Southfield Onc Inst/Michigan, U of 2Hawaii CCOP, Univ of 5 St Mary’s Hosp/St Louis University 2Upstate Carolina 5 Wooster Clinic/Cleveland Clinic OH 2Ozarks Reg CCOP 4 All Other Institutions 18St Charles Med Ctr/Puget Sound 4 Total (47 Institutions) 186Utah, U of 4


S9630/III



TOTALTamoxifen

aloneTamoxifenplus MPA

NUMBER REGISTERED 186 91 95






Tamoxifen alone(n=79)

Tamoxifen plus MPA(n=82)

AGE

Median 59.0 58.5Minimum 42 41Maximum 82 79

RACE

White (Non-Hispanic) 69 87% 76 93%Black (Non-Hispanic) 2 3% 1 1%Hispanic 3 4% 1 1%Asian or Pacific Islander 4 5% 4 5%American Indian 1 1% 0 0%

PRIOR ADJUVANT CHEMOTHERAPY

Yes 20 25% 26 32%No 59 75% 56 68%

NUMBER OF POSITIVE NODES

0-3 77 97% 75 91%4 or more 2 3% 7 9%


S9630/III


Toxicities with No Entries for Grades 2 to 5 Have Been SuppressedRegistrations ending December 31, 2000; Data as of February 15, 2001

Tamoxifen alone Tamoxifen plus MPA(n=38) (n=42)

Grade GradeTOXICITY Unk 0 1 2 3 4 5 Unk 0 1 2 3 4 5

Cardiovascular 0 32 3 2 0 0 1 1 34 7 0 0 0 0Endocrine 0 16 13 9 0 0 0 1 16 13 11 1 0 0Eye 1 37 0 0 0 0 0 0 41 0 1 0 0 0Flu-like Symptoms 0 19 14 5 0 0 0 1 26 6 8 1 0 0Gastrointestinal 0 34 3 1 0 0 0 0 37 3 2 0 0 0Hemorrhage 0 36 0 2 0 0 0 0 40 2 0 0 0 0Immunological 0 37 0 1 0 0 0 0 42 0 0 0 0 0Infection 0 37 0 1 0 0 0 0 40 0 1 1 0 0Liver 0 36 2 0 0 0 0 0 40 1 1 0 0 0Metabolic 0 37 1 0 0 0 0 0 41 0 1 0 0 0Miscellaneous 0 38 0 0 0 0 0 0 41 0 0 1 0 0Neurologic 1 31 4 2 0 0 0 0 28 9 5 0 0 0Pain 1 31 5 1 0 0 0 0 33 6 3 0 0 0Renal/Bladder 0 35 3 0 0 0 0 0 37 4 1 0 0 0Sexual/Reproductive Function 0 36 1 1 0 0 0 0 41 1 0 0 0 0 MAXIMUM GRADE ANY TOXICITYNumber 0 8 11 18 0 0 1 1 8 14 15 4 0 0


S9719/BIOLOGIC

S9719 Biologic

Clonal Hematopoiesis as a Marker of Genetic Damage Following AdjuvantChemotherapy for Breast Cancer: Pilot Study to Evaluate Incidence

Study Coordinators:M Slovak, C Willman, W Stock, K Albain, S Bearman


Data Coordinator:K Rantala


Date Closed:02/15/2001

ObjectivesTo estimate the incidence of early genetic damage,defined by the presence of clonal hematopoiesis usinga general clonality assay, the HUMARA (humanandrogen receptor assay), in pretreatment blood andbone marrow, apheresis, and two sequential post-treatment specimens in breast cancer patients enrolledin S9623.

To detect genetic damage following dose-intensiveadjuvant regimens for breast cancer by screening thesesamples for the presence of defective DNA mismatchrepair mechanisms and loss of heterozygosity usingmicrosatellite instability assays.

To estimate the incidence of MLL (myeloid lymphoidleukemia) gene fusion transcripts in cases where eitherthe HUMARA or microsatellite repeat assays arepositive for clonal hematopoiesis, a finding commonlyreported in t-AML with 11q23 abnormalities.

To determine the frequency of RAS gene mutations(H-, K-, and N-RAS) following dose-intensiveadjuvant regimens for breast cancer.

Patient PopulationPatients must be enrolled on S9623 and registered tothis biologic study before beginning protocol treatmenton S9623.

A pretreatment sample of peripheral blood, and bonemarrow when available, must be collected.

Accrual GoalsOne hundred patients per arm from S9623 will beaccrued on this study.

Summary StatementAs of December 31, 2000, there had been 26 reg-istrations to this study. The study closed along withS9623 on February 15, 2001.




TotalReg

Columbia River CCOP 7 Columbia University 1Oregon Hlth Sci Univ 3 Harris Methodist/San Antonio, U of TX 1Loyola University 2 Henry Ford Hosp 1Northwest CCOP 2 LSU-Shreveport 1St Francis/Stormont/Kansas, U of 2 N Colorado Med Ctr/Colorado, U of 1Arizona, U of 1 Salem Hospital/Oregon Hlth Sci Univ 1Carilion Medical Ctr/Loyola University 1 St Lukes/Mt States/Utah, U of 1City of Hope Med Ctr 1 Total (15 Institutions) 26


S9832/III

S9832 Phase III

Enhancing Well-Being During Breast Cancer Recurrence

Study Coordinators:C Gotay, C Moinpour, K Albain, S Martino, B Taylor

Statisticians:D Pauler, S Giarritta



Schema

RANDOMIZE

Telephone Counseling Intervention

Control (usual care)

First recurrence ofbreast cancer

ObjectivesTo assess the effectiveness of a telephone counselingintervention delivered by breast cancer survivors onwell-being of patients experiencing a first recurrence ofbreast cancer.

To examine the impact of sociodemographic, clinical,and psychosocial predictors of well-being in patientsexperiencing a first recurrence of breast cancer.

To examine changes in well-being over time sincerecurrence.

Patient PopulationPatients must have received definitive surgical treat-ment for Stage I, II, or IIIA breast cancer and havebeen diagnosed with a first recurrence of breast cancerwithin the past 56 days. "First recurrence" is defined asany distant metastatic site, or chest wall, scar, or nodalrecurrence (ipsilateral breast tumor recurrence follow-ing lumpectomy and isolated contralateral new primarybreast cancers are excluded).

Patients must not have a current psychiatric diagnosisthat would interfere with their ability to participate inthe intervention. Patients must be female. Patients mustbe able to read/understand English, and must havecompleted all baseline quality of life questionnaires.

Stratification/Descriptive FactorsTreatment randomization will be stratified by: (1) Age:< 50 years vs ��" �� #�� $�o-sis: < 2 years vs �� " �� %��&�tissue only vs bone with or without soft tissue vsvisceral with or without bone and/or soft tissue.


Accrual GoalsThree hundred eligible patients will be accrued to thisstudy.

Summary StatementAs of December 31, 2000, 171 patients had been reg-istered to this study. Twenty-one patients are currentlyineligible, 13 due to insufficient documentation.

In January 2001, the study was revised to eliminatespecifications about treatment for recurrence.

The quality of life form submission rates for patientsqualifying for assessments are as follows: baselineassessment, 97%; 3 month assessment, 89%; and6 month assessment, 85%.


S9832/III




TotalReg

Dayton CCOP 17 Bakersfield Mem Hosp/Los Angeles, U of CA 2Upstate Carolina 15 MedStar Onc Network/Davis, U of CA 2Northwest CCOP 10 Meridia South Pointe/Cleveland Clinic OH 2St Francis/Stormont/Kansas, U of 10 Sierra Nevada Mem/Davis, U of CA 2Greenville CCOP 8 Arkansas, U of 1New Mexico, U of 8 Baptist Health Sys/San Antonio, U of TX 1Columbia River CCOP 7 Colorado, U of 1Hawaii CCOP, Univ of 6 Columbia University 1Ozarks Reg CCOP 6 Huntington Mem Hosp/So Calif, U of 1South Alabama CCOP 6 Irvine, U of CA 1Wichita CCOP 6 Mercy Medical Center/Davis, U of CA 1Cleveland Clinic OH 5 Meridia Huron Hosp/Cleveland Clinic OH 1Columbus CCOP 5 Mt Sinai Med Ctr/Cleveland Clinic OH 1Duluth CCOP 5 N Colorado Med Ctr/Colorado, U of 1St Vincent Hlth Ctr/Cleveland Clinic OH 5 New Mexico MBCCOP 1East Alabama Med Ctr/Mississippi, U of 4 Northridge Hosp/Los Angeles, U of CA 1Grand Rapids CCOP 4 Providence Hosp 1St Jude Medical Ctr/Los Angeles, U of CA 4 Puget Sound 1Virginia Mason CCOP 4 Scott & White CCOP 1Horton Memorial Hosp/Columbia University 3 St Anthony Hosp/Oklahoma, Univ of 1John Muir Med Ctr/Davis, U of CA 3 Wayne State Univ 1Ozarks CGOP/Kansas, U of 3 Total (44 Institutions) 171Atlanta Reg CCOP 2



TOTAL Intervention Control NUMBER REGISTERED 171 85 86





S9832/III



Intervention(n=72)

Control(n=78)

AGE

Median 52 .0 52 .0Minimum 35 25Maximum 93 87

RACE

White (Non-Hispanic) 57 79% 66 85%Black (Non-Hispanic) 7 10% 4 5%Hispanic 3 4% 5 6%Asian or Pacific Islander 4 6% 2 3%American Indian 1 1% 1 1%

AGE

< 50 29 40% 35 45%�� 43 60% 43 55%

SITE OF RECURRENCE

Soft tissue only 27 38% 31 40%Bone +/- soft tissue 21 29% 24 31%Visceral 24 33% 23 29%

TIME SINCE FIRST DIAGNOSIS

< 2 yrs 17 24% 24 31%��\UV 55 76% 54 69%


S9927/III



Randomized Trial of Post-Mastectomy Radiotherapy in Stage II Breast Cancerin Women with One to Three Positive Axillary Nodes

Intergroup Participants:SWOG, ACOSOG, CALGB, ECOG, NCCTG, RTOG

Study Coordinators:L Pierce, T Pisansky (NCCTG), S Edge (ACOSOG),E Strom (RTOG), L Solin (ECOG), L Marks (CALGB)


Data Coordinators:D Lowry, S Edwards


Schema

*Prior to registration

RANDOMIZE

Observation

Chemotherapy*Mastectomy*andAxillary Dissection

Local-RegionalRadiotherapy

ObjectivesTo compare overall and disease-free survival in pre-and post-menopausal women with Stage II breastcancer and 1-3 positive nodes treated with or withoutradiation therapy following mastectomy and adjuvantchemotherapy.

To assess local-regional control for this cohort ofpatients.

To assess the potential toxicities of radiotherapy deliv-ered using CT-directed treatment in this cohort ofpatients.

Patient PopulationPatients must have histologically confirmed adeno-carcinoma of the breast, with the primary tumor ��and 1-3 positive axillary lymph nodes. Patients mustnot have pathologic N3 or T3 disease, or clinical orpathologic N2 or T4 disease, or M1 disease. Patientsmust not have gross extracapsular disease or residualdisease in the axilla. Patients with apocrine, adeno-

cystic, or squamous carcinomas or sarcomas of thebreast or bilateral breast cancer are not eligible.

Patients must have undergone a modified radicalmastectomy sparing the pectoralis minor muscle with alevel I and II axillary dissection. A minimum of 10nodes must have been removed and pathologicallyexamined. Surgical margins at time of mastectomymust be negative for both invasive carcinoma and fornon-invasive ductal carcinoma. Patients who haveundergone mastectomy after local failure followinglumpectomy are not eligible. Patients must be reg-istered such that radiation therapy begins within eightmonths after mastectomy and within six weeks ofcompleting systemic chemotherapy. Patients must havereceived chemotherapy with or without hormonaltherapy after mastectomy. Patients must not havereceived any prior trastuzumab therapy. Patients mustnot have received any prior chemotherapy except fortreatment of the current breast cancer. Patients must not


S9927/III

have received prior chest wall or nodal radiationtherapy at any time for any reason.

Patients must be at least 21 years of age and have aZubrod performance status of 0-1.

Stratification/Descriptive FactorsPatients will be stratified according to systemic che-motherapy: (1) Adriamycin or Epirubicin: yes vs no;(2) taxane: yes vs no; and (3) duration of chemother-apy: < 3 months vs 3-6 months vs > 6 months.

Accrual GoalsThe accrual goal is 2500 eligible patients. Formalinterim analyses will be performed after approximately75% of patient accrual is complete and againapproximately 1.5 years after completion of accrual.

Summary StatementThis study was opened on June 15, 2000. Four patientshad been enrolled as of December 31, 2000.



InstitutionsTotalReg

Columbia River CCOP 2CALGB 1N Michigan Hosp/Wayne State Univ 1 Total (3 Institutions) 4


S0012/III

S0012 Phase III

A Randomized Comparison of Standard Doxorubicin and CyclophosphamideVersus Weekly Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as

Neoadjuvant Therapy for Inflammatory and Estrogen-Receptor NegativeLocally Advanced Breast Cancer

Study Coordinators:G Ellis, R Livingston



Schema

RANDOMIZE AC + G-CSF weekly x 15 weeks

AC x 5 cycles (21 day cycle)

Resection with AxillaryNode Dissection

ObjectivesTo compare the pathologic microscopic response ratein patients treated with weekly doxorubicin and dailyoral cyclophosphamide given with G-CSF support tothat in patients treated with the standard doxorubicinand cyclophosphamide regimen given every threeweeks.

To compare the toxicities of these two regimens.

To compare the delivered dose intensity of these tworegimens.

To assess the association between pathologic completeresponse and clinical complete response at the primarytumor site in these patients.

Patient PopulationPatients must have a histologically confirmed diagnosisof locally advanced or inflammatory breast carcinoma.Patients with locally advanced, non-inflammatorybreast cancer must be estrogen receptor negative.Patients must have selected Stage IIB or selected

Stage III disease judged primarily unresectable by anexperienced breast surgeon. There must not be meta-s-tatic disease.

Patients must not have received any prior chemo-ther-apy for any cancer.

Patients must have adequate cardiac, hematologic,renal, and hepatic function and a Zubrod performancestatus of 0-2. Known HIV positive patients are in-eligible. Patients with hypertension or age > 60 yearsmust have a normal baseline MUGA scan or echocar-diogram.

Stratification/Descriptive FactorsPatients will be stratified by disease status: inflam-ma-tory vs other.

Accrual GoalsThe accrual goal is 150 eligible patients per arm. Oneinterim analysis will be performed after microscopicpathologic CR status is determined on the first 150patients.


S0029/II

S0029 Phase II

Single Agent Docetaxel for Metastatic Breast Cancer in PatientsAged 70 and Older

Study Coordinators:S Martino, K Albain


Data Coordinators:K Rantala, L Crowley

ObjectivesTo assess the feasibility of enrolling patients aged 70years or older with advanced breast cancer to astructured Phase II trial including pharmacokineticsampling.

To assess overall survival, two-year survival andresponse (confirmed and unconfirmed complete andpartial) in this elderly population when treated withdocetaxel.

To estimate the toxicity and tolerability of the regimenin this specific population group.

To assess the feasibility of using standardized selfreport measures of comorbidity, depression andfunctional status in an elderly population of patientswith cancer.

To assess parameters of clinical pharmacology ofdocetaxel in patients aged 70 years and older, includinghalf life value(s), AUC and steady state levels.

To assess whether patients under 60 years have clinicalpharmacologic parameters similar to those reported inthe literature (to validate our assay system).

To explore, at a preliminary level, the feasibility ofstudying genetic polymorphisms and gene expressionlevels of enzymes involved in drug metabolism andresistance to docetaxel in this patient population.

Patient PopulationPatients must be female with a pathologically con-firmed diagnosis of breast cancer. There must bemeasurable disease with histologic, cytologic or strongclinical evidence of distant metastasis. Patients withknown brain or CNS metastases are not eligible.

Patients must not have received prior chemotherapy foradvanced metastatic or recurrent disease. Prioradjuvant or neoadjuvant chemotherapy is acceptable.Prior adjuvant or neoadjuvant paclitaxel or docetaxeltherapy is allowed as long as at least six months havepassed since the last dose. Any number of priorhormonal therapy regimens for either the adjuvantsetting or for metastatic disease is allowed.

Patients must be 70 years or older, or less than 60years, and they must have a Zubrod performance statusof 0-2. Patients known to be HIV positive are noteligible. Patients must have adequate renal, hepatic andhematologic function.

Stratification/Descriptive FactorsPatients are stratified by age: <60 years vs 70 years orolder.

Accrual GoalsSixty eligible patients aged 70 years or older will beaccrued. In addition, 20 eligible patients under age 60will be accrued.


S0102/II

S0102 Phase II

Docetaxel and Vinorelbine Plus Filgrastim for HER-2 NegativeStage IV Breast Cancer

Study Coordinators:J Gralow, R Livingston


Data Coordinators:L Crowley, J Barce

ObjectivesTo estimate one year survival in HER-2 negative StageIV breast cancer patients using a combination ofdocetaxel and vinorelbine with concurrent G-CSFsupport.

To estimate the response rate (both complete responseand partial response) and time to progression inpatients treated with this regimen.

To estimate the qualitative and quantitative toxicities ofthis regimen.

To obtain tissue blocks for the determination of thepresence of tumor cell beta-tublin mutation.

Patient PopulationPatients must be women with Stage IV, HER-2negative, microscopically confirmed carcinoma of thebreast. Patients must not have uncontrolled CNSmetastases.

Patients must have received no more chemotherapythan one prior adjuvant program for primary disease(as an adjuvant or neoadjuvant therapy). Patients mustnot have received prior taxane therapy (paclitaxel,docetaxel). Any ongoing hormonal therapy must bediscontinued prior to registration. Patients must havecompleted all prior chemotherapy at least six monthsprior to registration.

Patients must have a performance status 0-2 by theZubrod criteria with adequate hematologic and hepaticfunction. Patients must not have pre-existing clinicallysignificant peripheral neuropathy except for abnorm-alities due to cancer. Patients must not have sensitivityto E. Coli-derived proteins.

Accrual GoalsThe accrual goal is 90 eligible patients.


S0110/II

S0110 Phase II

Docetaxel and Carboplatin with Weekly Trastuzumab for HER-2 Positive,Stage IV Breast Cancer

Study Coordinators:J Kash, K Albain


Data Coordinators:S Edwards, J Barce

ObjectivesTo estimate one-year survival in HER-2 positive StageIV breast cancer patients who have received no priorchemotherapy for their Stage IV disease using acombination of docetaxel and carboplatin with weeklytrastuzumab.

To estimate the response rate (both complete responseand partial response) and time to progression inpatients treated with this regimen.

To estimate the qualitative and quantitative toxicities ofthis regimen.

To obtain tissue blocks for the determination of thepresence of tumor cell beta-tubulin mutation.

Patient PopulationPatients must be women with Stage IV, HER-2 positivecarcinoma of the breast. Tumor pathology and HER-2

status must have been microscopically confirmed eitherin the adjuvant setting or the metastatic setting. Patientsmust not have brain or CNS disease.

Patients must have received no prior chemotherapy fortreatment of their Stage IV breast cancer. Prioradjuvant chemotherapy is allowed except taxane orplatinum. Prior cumulative dose of doxorubicin cannotexceed 360 mg/m2.

Patients must have adequate hematologic, renal, andhepatic function, normal LVEF as determined byMUGA scan or echocardiogram, and a Zubrodperformance status of 0-2. Patients must not have pre-existing clinically significant peripheral neuropathyexcept for abnormalities due to cancer.

Accrual GoalsThe accrual goal for this study is 90 patients.

breast committee - swog 2001/breast.pdf · tamoxifen alone 15 32 3 91 tamoxifen plus mpa 16 26 10...

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