md anderson cancer center ccop research base update 2011 michael j. fisch, md, mph, facp chair,...

MD Anderson Cancer Center CCOP Research Base

Update 2011Michael J. Fisch, MD, MPH, FACP

Chair, Department of General Oncology

Division of Cancer Medicine

[email protected]

Twitter: @fischmd, @JSupportOncol

mailto:[email protected]

Objectives

• Review our membership and accrual• Discuss some study data• Describe and discuss our active studies• Summarize CCOP Strategic Plan• Explore our future together

– What do we do well?– What will be the indicators of success in the

future?

Active Treatment Protocols

2005-0839 (NCI 7341)A Phase II Study of Gemcitabine, Paclitaxel, and Doxorubicin, with Pegfilgrastim for the Treatment of Patients with Metastatic Transitional Cell Carcinoma and Renal Insufficiency

Principal Investigator: Lance C. Pagliaro, MD, MD Anderson Cancer Center

Methodology: Single-arm phase II protocol Patients with CrCL< 60 ml/min receive

• doxorubicin 40 mg/m2 IV over 20 min; • paclitaxel 135 mg/m2 IV over 60 min; • gemcitabine 900 mg/m2 IV over 90 min;

Pegfilgrastim 6 mg SC on day 1 or day 2 Courses repeated every 14 days

Patient Population: Metastatic or unresectable transitional cell (TCC) carcinoma of bladder, urethra

or upper urinary tract. Mixed TCC and variant histologies (small cell, squamous, adenocarcinoma,

sarcoma) are permitted if present in < 50% of the biopsy specimen. Accrual 28 patients / Goal 72

Top Enrolling Sites: MD Anderson, Ozarks CCOPPreliminary Results: Poster presented at GU ASCO February, 2011

Treatment: Active

Closed Treatment Protocols

ID00-156 (NCI 3410)A Prospective Randomized Phase III Trial Comparing Consolidation Therapy with or without Strontium-89 Following Induction Chemotherapy in Androgen-Independent Prostate Cancer

Principal Investigator: Shi-Ming Tu, MD, MD Anderson Cancer Center

Patient Population: A total of 265 patients with androgen-independent prostate cancer were enrolled. Closed to new patient entry 10/20/2010. Top Enrolling CCOP Sites: MD Anderson – Orlando, Marshfield Clinic, Wichita CCOP, Central Illinois CCOP Preliminary Results: Pending

Treatment: CNPE

Option 1Ketoconazole/doxorubicinAlternating withEstramustine/vinblastine

Option 2Prednisone/docetaxel

RANDOMIZE

Sr-89 plus doxorubicin x 6 weeks

Doxorubicin x 6 weeks

Clinical Response

16 weeks

2004-0662 (NCI 6636)A Randomized, Factorial-Design, Phase II Trial of Temozolomide Alone and in Combination with Possible Permutations of Thalidomide, Isotrentinoin and/or Celecoxib as Post-Radiation Adjuvant Therapy of Glioblastoma Multiforme

Principal Investigator: Mark R. Gilbert, MD, M. D. Anderson Cancer Center

Treatment: CNPE

Temozolomide Other Agent(s)

CR,PRorSD

PD

IneligibleCR=complete response, PR=partial response,

SD=stable disease, PD=progressive disease

TMZ-temozolomide; Thal-thalidomide;

CRA-cis-retinoic acid (isotretinoin); Cel-celocoxib

Reg

. & R

and

om.

RT

Max. =5 wks

Sur

gery

or

Bio

psy

1 TMZ None

2 TMZ + Thal

3 TMZ + CRA

4 TMZ + Cel

5 TMZ + Thal/CRA

6 TMZ + Thal/Cel

7 TMZ + CRA/Cel

8 TMZ + Thal/CRA/Cel

Patient Population: 178 patients with a diagnosis of supratentorial glioblastoma multiforme enrolled. Closed to new patient entry 02/24/2011.

Top Enrolling CCOP Sites: Atlanta CCOP, Kansas City CCOP, Central Illinois CCOP

Preliminary Results: Pending

2004-0305 (NCI 6485)A Phase II Study of Rituximab-CHOP with Pegylated Liposomal Doxorubicin in Patients Older than 60 Years of Age with Untreated Aggressive B-Cell Non-Hodgkin’s Lymphoma

Methodology:Rituximab 375 mg/m2 IVPB on day 1, administered 1st Cyclophosphamide 750 mg/m2 IVPB on day 1Pegylated liposomal doxorubicin 40 mg/m2 IV over 1hr day 1 Vincristine 2.0 mg IV, day 1Prednisone 40 mg/m2 PO days 1-5GCSF 5 mcg/kg, SC daily, start on day 5, until neutrophil recovery (>3000/ul) ORPegylated GCSF 6 mg SC x 1 (24 hours after chemotherapy)

Patient Population: At total of 80 patients, older than 60 years of age with untreated aggressive B-cell NHL, enrolled. Closed to new patient entry 05/18/2009.

Top Enrolling CCOP Sites: Maimonides Medical Center, Grand Rapids CCOP

Treatment: CNPE


Summary of Protocol Findings– 80 patients were enrolled on the trial and evaluated for response,

cardiotoxicity, and myelosuppression. – 74 patients were evaluable for response after 4 courses of therapy.

– 54 (73%) patients achieved a CR / 14 (19%) patients achieved a PR

– The overall response rate was 92%. – Response assessment after 8 courses of therapy was performed on

63 evaluable patients. – The overall response rate for the 63 evaluable patients after

8 cycles was 89%.

Treatment: CNPE


Summary of Protocol Findings– Of the 80 patients enrolled, 12 (15%) patients reported grade 3

cardiac events, including hypotension (3), tachycardia (1), hypertension (2), decreased ejection fraction (1), chest pain (2), arrhythmia (3), coronary artery disease (1), acute coronary syndrome and diastolic dysfunction (1), TIA (1), and pericarditis (1).

– Other Grade 3-4 toxicities reported in >10% of patients were: fatigue (27), leucopenia (31), lymphopenia (35), neutropenia (34), and anemia (12).

Treatment: CNPE

2006-0260 (NCI 7548)Single-arm, Open-label, Phase II Trial of Rituximab plus Sargramostim for the Treatment of Newly Diagnosed Follicular B-cell Lymphoma in Adults

New Principal Investigator Nathan Fowler, MD, MD Anderson Cancer Center

Patient Population: A total of 52 patients with newly diagnosed follicular B cell lymphoma were enrolled. Closed to new patient entry 05/01/2009.

Top Enrolling CCOP Sites: Wichita CCOP, Grand Rapids CCOP

Treatment: CNPE


Summary of Protocol Findings– 52 pts were enrolled on study, and all were eligible for

assessment. The median age was 56 (31-78), and 62% were male.

– 56% of patients had intermediate or high risk FLIPI. Fifteen (29%) pts had bulky disease (>5cm), and 29 (56%) pts had elevated B2M.

– Tolerance was good; and effects attributable to GM-CSF were minor. Absolute granulocyte count (AGC) elevation above 15K occurred in only 4% of pts; conversely, ≥ grade 3 neutropenia occurred in 8 pts. No significant infections occurred.

Treatment: CNPE


Summary of Protocol Findings– At 3 months, the overall response rate was 69%, including 23%

of pts with a CR. With continued follow up, response rates improved (ORR 74%, CR 42%). Twenty four (46%) pts remain in remission without further treatment. At a median follow up of 14 months the median PFS of all pts was 28 months, including pts with bulky disease (median PFS of 16 mo). No difference in PFS was observed when comparing FLIPI score (0-1) vs (2-3) or B2M.

– Conclusion: Rituximab plus GM-CSF is well tolerated and active in untreated pts with FL. There did not appear to be significant difference in outcomes when comparing FLIPI scores, although PFS was inferior in patients with bulky disease. Randomized studies are required to determine whether this combination is superior to rituximab as a single agent.

Treatment: CNPE

Active Cancer Control Protocols

2004-0024 (NCI CCC01-06)Chemotherapy and Mindfulness Relaxation: A Randomized Trial at M. D. Anderson Cancer Center and M. D. Anderson Community Clinical Oncology Program

Principal Investigators: Jon Hunter MD, Mount Sinai Hospital, Toronto Lorenzo Cohen, PhD, MD Anderson Cancer Center

Community Co-Investigator: Dedra Glover, AS, CCRP, Scott & White CCOP

Methodology: Patients with newly-diagnosed cancer, who are about to undergo chemotherapy, and give informed consent, will be randomly assigned to one of three groups:

• Mindfulness Relaxation group [MR]; • Relaxing Music group [RM] where participants will listen to music for the same

amount of time as the MR participants receive their intervention; • Standard Care control group where participants will receive standard medical

education on chemotherapy [SC].

Patient Population: The study population will consist chemotherapy naive cancer patients schedule to undergo at least 4 cycles of chemotherapy treatment. Target accrual 400 subjects (including 25 on pilot). Current accrual 284.

Top Enrolling CCOP Sites: Scott & White CCOP, Michigan Cancer Research Consortium, San Juan MBCCOP

Cancer Control: Active

2004-0024 (NCI CCC01-06)Chemotherapy and Mindfulness Relaxation: A Randomized Trial at M. D. Anderson Cancer Center and M. D. Anderson Community Clinical Oncology Program

Additional training and intervention recording being held March 5, 2011.

Planned protocol revision March, 2011 to remove exclusion criteria excluding patients with concrete planned immune therapy as part of the their treatment regimen and/or within 3 months of completing chemotherapy. Examples include GCSF, GMCSF,IL2, and/or Interferon.

2006-0198 (NCI MDA 2006-0198)CAM Use and Cancer

Principal Investigator: Patricia Ann Parker, PhD, MD Anderson Cancer Center

Patient Population:. Oncology nurses with regular interactions with patients who are at least one week post diagnosis of cancer and not greater than 6 months post treatment. 1360 target accrual.

Top Enrolling CCOP Sites: Metro-Minnesota CCOP, Central Illinois CCOP, Grand Rapids Clinical Oncology Program, Boston Medical Center


Baseline Patient Assessment

Random Assignment to Intervention or Waitlist Control

Baseline Provider Assessment

CD/Video and Resource List

Baseline Provider Assessment

Enrollment of Nurses/Providers at Participating CCOPs

CD/Video and Resource List

1 Week

Provider and Patient Follow-Up Assessment Provider and Patient Follow-Up Assessment2 Weeks

Provider and Patient Follow-up Assessment Provider and Patient Follow-up Assessment2 Months

Preliminary Findings – ASCO 2010

– Patients were 65% female, 86% non-Hispanic white,

average age of 59 (range 23-88), and 30% had a

college degree or higher.

– The most common cancers were breast cancer

(31%), lung cancer (12%), and colorectal cancer

(10%).

– 39% indicated that they have used one or more CAM

therapies following their cancer diagnosis.




Preliminary Findings Continued– The most common categories of CAM used by

patients were:• massage therapy (19%) • relaxation techniques (19%) • special diet (18%) • megavitamins (15%)

– Reasons for using CAM included: • believes CAM beneficial (27%) • to address the emotional and spiritual aspects of the disease

(23%) • and to boost immune system (21%)



Preliminary Findings Continued– Patients indicated that 9% of their physicians and 12% of nurses

had asked them about their use of CAM at that oncology visit. – Twenty-one percent of patients reported that they initiated a

discussion with their providers about their use of CAM and the most common responses were: encouraged me to continue (13%) and was neutral (7%).

– Reasons for not telling healthcare practitioners about CAM use included: my healthcare provider never asked (27%) and unsure if CAM beneficial (18%).



Conclusions:More than one third of patients indicated that they used some type of CAM therapy and the majority of their providers did not ask them about their CAM use. There remains considerable uncertainty among patients about the role of CAM in the context of cancer care.


Twitter Time!

@fischmd

@JSupportOncol

@disparityreport

@DrLCohen

Promote Clinical Trials

Instantly share IRB approved clinical trial flyers with a global audience

1. Uploaded approved flyer to web server2. Shorten URL at http://bit.ly3. Paste trial title and URL into Twitter

update box.4. Done!

Why Bit.ly?5. Shortens URL – Twitter limits you to 140

characters6. Metrics. See how many people click on

your links.

This process works with any file type. It isn’t just for clinical trials.

http://bit.ly/

Focused DiscussionsHashtags are keywords that “tag “ a conversation so that readers can easily find all relevant tweets/comments. They’re great for conferences!

Creating a hashtag is easy1. Any word in your tweet that starts with a pound sign is a hashtag. That’s all you have to do

Twitter makes hashtags “clickable” automatically. Clicking on one reveals the entire conversation thread. You can create your own or use others (as long as your input is relevant).

Examples:#mdacctrials#pediatrics#oncology#ASPHO2010

2006-0841 (NCI MDA 2006-0841) Randomized, Double-Blind, Placebo-Controlled Trial of Palonosetron/ Dexamethasone with or without Dronabinol for the Prevention of Chemotherapy-induced Nausea and Vomiting after Moderately Emetogenic Chemotherapy

Principal Investigator: P. K. Morrow, MD, MD Anderson Cancer Center Steven Grunberg, MD, University of Vermont

Community Co-Investigator: Jeffery Giguere, MD, Greenville CCOP

Methodology:

Palonosetron 0.25 mg IV and dexamethasone 10 mg IV 30 minutes prior to chemo administration. Randomized to take dronabinol 5 mg or matched placebo: 1 tablet by mouth 3 times a day for 5 days beginning 30 minutes before chemotherapy.

Follow-up physical examination and assessment between day14 through 28.

Primary endpoint will be Total Protection: No Vomiting, No Rescue Therapy and no Nausea during the overall (0-120 hour) period.

Patient Population: Population will be 100 patients in each treatment group (200 patients total). Patients ≥18 years old, documented solid tumor, receiving first time chemotherapy. Currently 40 enrolled of 200 target accrual.

Enrolling CCOP Sites: Christus St. Frances Cabrini, Marshfield Clinic, Greenville CCOP


2006-0841 (NCI MDA 2006-0841) Dronabinol/Placebo for the Prevention of CINV for Moderately Emetogenic Chemotherapy

– Planned protocol revision March, 2011– Allow the addition of regimens that give taxanes before Adriamycin

and/or Cytoxan– Patients will be eligible after any number of cycles if

– taxane given as part of planned regimen such T→AC– Patient has no N/V with taxane cycles


2008-0005 (NCI MDA 2008-0005)Phase II, Randomized, Double Blind Comparison of CASAD vs. Placebo for the Treatment and Prevention of Diarrhea in Patients with Metastatic Colorectal Cancer

Principal Investigator: Bryan Kee, MD, M. D. Anderson Cancer Center

Methodology:

CASAD / placebo will be provided by Salient Pharmaceuticals incapsules that are taken as 2 capsules four times daily.

Recently revised and sent to sites for approval. Major changes: inclusion of patients with ostomies, less restrictive lab requirements including ANC, and revision of UGT1A1 criteria.

Patient Population: A maximum of 100 patients will be randomized equally between two arms, 50 per arm. Current accrual 56.

Enrolling CCOP Sites: Scott & White CCOP, Greenville CCOP, Columbia River CCOP


R

6 WeeksCASAD -------------------------- Off Study/Optional Additional 6 Weeks

Placebo -------------------------- Off Study/Optional Additional 6 Weeks

2007-0914 (NCI 2007-0914a)A Multi-Center Study in Patients Undergoing Anthracycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment

Principal Investigator: Daniel J. Lenihan, MD, Vanderbilt UniversityMichael Fisch, MD, MD Anderson Cancer Center

Community Co-Investigator: Steven Wolff, MD, Meharry Medical College MBCCOP

Methodology:The biomarkers (BNP and Troponin I) will be obtained as a point of care test with meter, kits, controls and training provided by the protocol. Patients will be assessed during each visit prior to each cycle of therapy until therapy completion and then at 6 and 12 months after the initiation of chemotherapy to identify cardiotoxicity.

Patient Population: A total of 830 patients starting a new anthracycline chemotherapy regimen will be enrolled.

Enrolling CCOP Sites: Meters, kits and controls have been provided to 18 CCOP, Main Member and academic sites. Additional meters will be available in March, 2011. Currently 9 enrolled of 830 target.



Eligible Diseases• Most enrollments will be patients with Non-Hodgkin’s Lymphoma or

breast cancer

• Can be any disease being treated with a regimen that uses an

anthracycline including: Hodgkin’s, multiple myeloma, AML, ALL,

sarcoma, Kaposi’s sarcoma, bladder, SCLC, NSCLC, gastric,

ovarian and prostate



Acceptable Anthracyclines• doxorubicin (Adriamycin) • doxorubicin liposomal (Doxil) • daunorubicin (Cerubidine)• daunorubicin liposomal (DaunoXome)• epirubicin (Ellence)• idarubicin (Idamycin)• mitoxantrone (Novantrone)• valrubicin (Valstar)



Length of anthracycline regimen: – Any, Q14 days, Q21 days, Q28 days

Anthracycline administration:– Bolus or continuous infusion

Minimum anthracycline dose: – any

Anthracycline regimen: – single agent or multiple agent regimen



Echocardiogram– Prefer echocardiogram – May use Muga scan if used consistently throughout

the trial– Muga provides limited information, is more expensive,

and exposes patient to more radiation

Protocol revision in progress to clarify this point


2009-0288 (MDA 2009-0288)Comparative Study of Oncologist Recommended, Home-Based Exercise Program and Relaxation Training for Physical Functioning and Symptom Control in Colon Cancer Patients

Principal Investigator: Karen Basen-Engquist, PhD, MD Anderson Cancer Center

Methodology:

Patient Population: A total of 150 patients with metastatic colon cancer will be accrued to this protocol.

Enrolling CCOP Pilot Sites: Wichita CCOP, Scott & White CCOP, Michigan Cancer Research Consortium. Currently 2 enrolled of 150 target.


N=150 R

16 Week Exercise Program 16 Week Relaxation Program

Brief advice and letters from physician Brief telephone counseling Newsletters Written and video instructions for

resistance exercises, resistance bands and pedometer

Brief advice and letters from physician Brief telephone counseling Newsletters Written and audio instruction for

relaxation exercises

Closed Cancer Control Protocols

2004-0728 (NCI CCC 03-27)Prevention of Cisplatin- or Oxaliplatin-induced Peripheral Neuropathy with Alpha-lipoic Acid: A Placebo-controlled Phase III Trial

Principal Investigator: Ying Guo, MD, MD Anderson Cancer Center

Methodology:

Patient Population: A total of 244 patients who were scheduled to receive chemotherapy that contains platinum in the regimen were enrolled. Closed to new patient enrollment 11/02/2009.

Top Enrolling CCOP Sites: Metro-Minnesota CCOP, Wichita CCOP, Greenville CCOP, Marshfield Clinic, Christus St Frances Cabrini Hospital

Cancer Control: CNPE

Platinum Therapy (Schema overview for CCOP patients enrolled)

Placebo

TID

**Functional Tests• Time to button 6-hole shirt• 50-foot walk at fastest speed• Coin test

Rand

om

ization

*

Total Prior Total Prior*Stratum Cisplatin Rx* Oxaliplatin Rx*

1 <200 mg/m2 <750 mg/m2

2 200-399 mg/m2 750-999 mg/m2

3 >400 mg/m2 >1000 mg/m2

*For patients previously exposed to both drugs,the following formula will be used. If “X mg/m2” of Cisplatin and “Y mg/m2” of oxaliplatin had been received, a “calculated prior cisplatin dose”, Z, will be used for stratification in the cisplatin column.

Z=Y/3 + X

ALA 600 mg

TID

Week 6±1

Week 12±1

Week 24±1

FA

CT

/GO

G-N

TX

, B

PI,

Functio

na

l T

ests

**

ALA 600 mg

TID

ALA 600 mg

TID

Placebo

TID

Placebo

TID

Week 36 ±1 Week 48 ±1

No treatment No treatment

No treatment No treatment

FA

CT

/GO

G-N

TX

, B

PI,

Functio

na

l T

ests

**

FA

CT

/GO

G-N

TX

, B

PI,

Functio

na

l T

ests

**

FA

CT

/GO

G-N

TX

, B

PI,

Functio

na

l T

ests

**

FA

CT

/GO

G-N

TX

, B

PI,

Functio

na

l T

ests

**

FA

CT

/GO

G-N

TX

, B

PI,

Functio

na

l T

ests

**

Chemotherapy cycles most likely will be received by patients

Chemotherapy cycles possibly will be received by patients


Of 243 pts randomized, 121 pts (51%) completed treatment for 12 weeks. At 24 weeks, only 34 evaluable pts remained in the ALA group, and 36 in the placebo group (p= 0.75). No statistical difference was noted in dose intensity for the oxaliplatin arm of the ALA group and the placebo group (median of 765 mg/m2 vs. 1020 mg/m2, p=0.18).

No significant differences were noted for either FACT/GOG-NTX scores (p=0.70), neurotoxicity (p=0.87), or best tumor responses between the 2 groups (p=0.85).



Conclusions: • Oral ALA 600 mg PO TID was ineffective at preventing neurotoxicity

caused by oxaliplatin or cisplatin. • Intense schedules of oral agents in the symptom/toxicity prevention

setting created adherence challenges due to pill size and frequency of administration.

• Poor adherence might affect the power to detect ALA’s effectiveness in this trial.

• Innovative drug delivery and trial designs are needed to further explore alpha lipoic acid in the prevention and/or reduction of chemotherapy-induced neuropathy.


Upcoming Protocols

2010-0547 (MDA 04-01)A Phase III Prospective Randomized Trial of Acupuncture for Treatment of Radiation-Induced Xerostomia in Patients with Head and Neck Cancer

Principal Investigator: Joseph S. Chiang, MD, MD Anderson Cancer Center

Methodology:

Protocol Status: NCI Approved, IRB Approval PendingPatient Population: A total of 150 patients who have received radiation for the treatment of head and neck cancer will be enrolled. Enrolling CCOP Sites: Sites should have a relationship with board certified acupuncturists who will participate in training to do fixed acupuncture on a placebo controlled protocol.

Cancer Control: Proposed

2010-0547 (MDA 04-01)A Phase III Prospective Randomized Trial of Acupuncture for Treatment of Radiation-Induced Xerostomia in Patients with Head and Neck Cancer

• Conference call/webinar to be held with interested sites in March, 2011.

• Call will be led by faculty from the Integrative Medicine Program– Lorenzo Cohen, PhD – Kay Garcia, MSN, MPH, DrPH (acupuncturist)

• Subcontracts will be implemented with participating sites to provide pass through funds for acupuncture.

• Training videos will be provided for sites/acupuncturists


2011-0147(Not Yet Assigned)A Phase I Study of Sublingual Anvirzel (Nerium Oleander) in Advanced Non-Small Cell Lung Cancer

Principal Investigator: Richard Lee, MD, MD Anderson Cancer Center

Methodology: All subjects will receive SL Anvirzel dosing beginning 3 days prior to starting chemotherapy. A total of four dose cohorts will be evaluated (0.8, 1.6, 2.4, 3.2 ml/m2/day; SL q8hrs) with 7 patients per cohort.

Protocol Status: NCI Concept Submission Pending

Patient Population: Newly diagnosed advanced non-small cell lung cancer patients scheduled to receive four cycles of carboplatin and docetaxel chemotherapy. Total accrual goal of 28 patients.


Not Yet Assigned

Nano-curcumin in Breast Cancer Prevention in the Contralateral Breast

Principal Investigator: Banu K. Arun, MD, MD Anderson Cancer Center


Patient Population: Breast Cancer Patients


Not Yet Assigned

BIG Study: Time Out for Reflection in the Course of Chemotherapy

Principal Investigator: Jon Hunter, MD, Mount Sinai Hospital, Toronto, Michael J. Fisch, MD Anderson Cancer Center, Lorenzo Cohen, PhD, MD Anderson Cancer Center


Patient Population: Cancer Patients


CCOP Strategic Plan

• Incoroporate emerging science and novel trial designs– Survivorship, tx toxicities, risk assessment

• Use epi and biologic data from underrepresented populations

• Improve clinical trial participation

Winning the future?

• What are our biggest assets at MDACC?• What do we do best?• What should we do best (but aren’t yet)?• Creative ideas moving forward?

Thank [email protected]

(713) 563-0276

md anderson cancer center ccop research base update 2011 michael j. fisch, md, mph, facp chair,...

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