rtog lung cancer committee 2012 clinical trial...

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RTOG Lung Cancer Committee

2012 Clinical Trial Update

Wally Curran

RTOG Group Chairman

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RTOG Lung Committee: Active Trials

• Small Cell Lung Cancer

– Limited Stage (Intergroup Trial)

– Extensive Stage (RTOG 0937)

• Early Stage NSCLC

– In-operable (0813 and 0915)

– Operable (RTOG 1021 / ACOSOG Z4099)

• Locally advanced NSCLC

– Stage IIIA with minimal N2 disease (0839)

– Stage IIIA –Individualized RT Rx with PET-adapted boost (1106)

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Phase III Comparison of Thoracic

Radiotherapy Regimens in Limited-

stage Small Cell Lung Cancer

CALGB 30610

RTOG 0538

Principal Investigator: Jeff Bogart, MD

RTOG PI: Ritsuko Komaki, MD

CDDP VP-16

CDDP VP-16

CDDP VP-16

CDDP VP-16

70 Gy Gy, 2.0 Gy QD

61.2 Gy, 1.8 Gy QD FB Con bst

CDDP VP-16

CDDP VP-16

CDDP VP-16

CDDP VP-16

PCI

45 Gy 1.5 Gy BID

CDDP VP-16

CDDP VP-16

CDDP VP-16

CDDP VP-16

R

A

N

D

O

M

I

Z

E

CALGB 3060/RTOG 0538

(months)

0 4 8 12 16 20 24 28 32 36

0

10

20

30

40

50

60

70

80

90

100

PCI

Control

1 year: VS.

HR: 0.68 (0.52-0.88) p=0.003

Overall survival

Prophylactic cranial irradiation in

extensive disease small cell lung cancer

13.3% 27.1%

Slotman et al. NEJM 2007

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Study Design

PCI

25 Gy in 10 fx

RT to

Chest and

Other Sites

Random Any response Chemotherapy

(4-6 cycles)

Phase II Study of PCI and consolidative

Extra-Cranial Radiation for ED-SCLC

RTOG 0937

Observation

PI: Elizabeth Gore, MD

Stratify:

PR vs CR

1 vs 2-3 mets

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RTOG 0937 Specifics

• Primary Objective: To compare 1-year median survival

• Eligibility:

– ES-SCLC, excluding brain metastases AND

– Only 1-3 metastatic sites prior to platinum-based

chemotherapy AND

– Radiographic PR or CR

• Sample size = 154

• Radiation therapy dosing

– PCI given in 2.5 Gy fractions to 25 Gy

– Metastases dosing is 3 Gy fractions to 45 Gy

– Acceptable alternative is 4 Gy fractions to 40 Gy

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RTOG Lung Committee


– Limited Stage (Intergroup Trial)

– Extensive Stage (RTOG 0937)


– In-operable

– Operable (RTOG 1021 / ACOSOG Z4099)


– Stage IIIA with minimal N2 disease (0839)

– Stage IIIA with PET-adapted boost (1106)

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Physical Targeting with SBRT

RTOG 0813

Phase I/II study of SBRT for early stage centrally located NSCLC in medically

inoperable pts

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RTOG 0813 - SBRT Dose Levels

Level 5 10.0 Gy x 5 50.0. Gy

Level 6 10.5 Gy x 5 52.5 Gy

Level 7 11.0 Gy x 5 55.0 Gy

Level 8 11.5 Gy x 5 57.5 Gy

Level 9 12.0 Gy x 5 60.0 Gy

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RTOG 0915-SBRT for early stage

medically inoperable lung cancer

12 Gy x 4

R

e

g

i

s

t

e

r

34 Gy X 1 Primary Endpoint

> grade 3 rates of Toxicity Respiratory

Soft tissue/chest wall

Skin

Secondary Endpoints

LC/OS/DFS

PET response

PFTs

Biomarkers

R

a

n

d

o

m

i

z

e

VS.

PI: Videtic

12 Gy X 4

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• Medically Inoperable Early Stage NSCLC

RTOG SBRT Plan

Randomize III

SBRT 34 Gy X 1

SBRT 12Gy X4

SBRT (18 Gy X 3)

Altered Fx SBRT

Randomize II

RTOG 0915

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Histological

confirmed

Stage I

NSCLC Registration

and

Randomization

ARM 1:

Sublobar

Resection ±

Brachytherapy

(SR)

ARM 2:

Stereotactic

Body

Radiation

Therapy

(SBRT) 18 Gy

X 3 = 54 Gy

F

O

L

L

O

W

U

P

ACOSOG Z4099/ RTOG 1021

H. Fernando, MD (ACOSOG);

R. Timmerman, MD (RTOG)

Activated June 2011

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ACOSOG Z4099/ RTOG 1021

• 400+ patient randomized trial

– Enrolled in 4-5 years (8 patient/month)

• Primary endpoint is 3 year overall survival

• Randomize prior to treatment

– Intent to treat

– +/- brachytherapy is optional in surgery arm

• CTC Version 4 toxicity assessment for both arms

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RTOG Lung Cancer Strategy


– Limited Stage

– Extensive Stage


– In-operable

– Operable


– Stage IIIA with minimal disease

– Stage IIIA with PET-adapted boost

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RTOG 0229: Phase II Trial of Concurrent Chemo and Full

Dose RT Followed by Surgical Resection and Consolidative

Tx for LA NSCLC

Induction Chemo-RT Paclitaxel and Carboplatin 1x/week for 6 weeks plus Concurrent RT to 61.2 Gy

Reassessment of Mediastinum: 4 weeks post Induction Chemoradiation

Resection Within 2 wks of Reassessment

Not Resectable

Consolidation Chemotherapy No later than 10 weeks post-surgery Pacilitaxel and Carboplatin q

21 days x 2

(Prophylactic Cranial Irradiation, if indicated)

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Tumor Characteristics

(n=57)

Histology

Squamous Cell Carcinoma 11 (19.3%)

Adenocarcinoma 29 (50.9%)

Large cell undifferentiated 1 ( 1.8%)

NSCLC, NOS 16 (28.1%)

AJCC Stage

IIIA 56 (98.2%)

IIIB 1 ( 1.8%)

T-Stage

T1 18 (31.6%)

T2 28 (49.1%)

T3 11 (19.3%)

N-Stage

N2 56 (98.2%)

N3 1 ( 1.8%)

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Mediastinal Nodal Clearance

Residual Mediastinal Disease

Mediastinal nodal clearance

Patients Eligible for Assessment of Primary Endpoint

Surgery Performed

Reasons for No Surgery

Residual Mediastinal Nodes

Primary Unresectable

Medical contraindications

MD refusal

Died prior to Surgery

Progressive disease

Other

(N=43*)

16 (37%)

27 (63%)

43 Pts

37 pts

20 pts

6 pts

2 pts

5 pts

1 pt

1 pt

1 pt

4 pts

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Survival

Time (Months)

Overall Survival

% Alive (95% Cl) # at Risk

Progression-Free Survival

%Alive (95% Cl) # at Risk

0

6

12

18

24

100% 57

87.7% (76.0, 93.9) 50

77.2% (64.0, 86.1) 43

66.4% (52.5, 77.1) 37

53.8% (40.0, 65.8) 29

100% 57

75.4% (62.1, 84.7) 43

50.8% (37.2, 62.9) 28

38.1% (25.6, 50.5) 21

32.7% (20.9, 45.0) 17

Fail/Total

Median

(95% Cl)

32/57

26.6 months

(18.5, ∞)

45/57

12.9 months

(8.0, 18.8)

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Overall Survival by Mediastinal

Nodal Clearance Status

Time (Months)

No Mediastinal Nodal

Clearance


Mediastinal Nodal

Clearance


0

6

12

18

24

100 % 16

87.5% (58.6, 96.7) 14

81.3% (52.5, 93.5) 12

60.9% (32.7, 80.3) 9

54.2% (27.1, 75.0) 8

100% 27

100% 27

92.6% (73.5, 98.1) 25

81.5% (61.1, 91.8) 22

66.7% (45.7, 81.1) 17

Fail/Total

Median Survival

Time (95% Cl)

8/16

32.7 months (13.8, ∞)

12/27

Not Reached

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NSCLC IIIA CBDCA AUC =2.0

Paclitaxel 50 mg/m2

XRT 61.2 Gy (1.8 Gy/d) Panitumumab

Resectable Y N

• Anatomic lobectomy or pneumonectomy

• Muscle flap for bronchial stump

CBDCA AUC=6

Paclitaxel 225 mg/m2

x 2 cycles

Tissue: MALDI-TOF

Specimens for

proteomic analysis & other

correlative studies

Resection:

MALDI-TOF & other

specimens

RTOG 0839

PI: Martin Edelman, MD

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Thinking newer strategies

• Personalized medicine – AM4/ALK and EGFR mutation trial

– Wild-type (non mutant) trial

• Adaptive XRT (RTOG 1106) – Mid-treatment FDG-PET based target volumes

adapted radiation therapy

– Isoeffect radiation dose prescriptions

– Why? • PET tumor volumes shrink during XRT

• May incorporate all Stage III patients, not just those selected to get 74 Gy based on NTCP

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RTOG 1210/ Alliance 31101

Submitted to NCI 7/12

Stage III NSCLC With either EGFR TK mutation or ALK Fusion

ALK Fusion +: Crizotinib 3 months

A Randomized Phase II Trial

EGFR Mutation + Erlotinib 3 months followed by

ChemoRT* Alk Fusion +

Crizotinib 3 months followed by ChemoRT*

*Pemetrexed 500 mg/m2 q 3 weekly x 4 Carboplatin AUC 5 (4 cycles) with Thoracic Radiation 64 Gy

EGFR Mutation+/Alk Fusion+ ChemoRT* ONLY

Experimental

Control

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PET-based Adaptive RT for Stage III

NSCLC

RTOG 1106: Just Activated!!

R E G I S T E R

ChemoRT 44 Gy FDG-PET

SD/Response

PD

FDG-PET

Off Study – D/C RT

RT to 64 Gy

R A N D O M I Z E

RT to 64 Gy + 10+ Gy boost based on FDG-PET

Tumor Volume Reduced During-RT

(UMCC 2003-76, UMCC 2006-040)

Change in PET-MTV

04080

120160200240280320360400

Pre-RT During-RT Post-RT

PE

T-M

TV

(cc)

Change in CT-GTV

0

50

100

150

200

250

300

350

400

450

500


CT

-GT

V (

cc)

020406080

100120140160180200

PE

T-M

TV

(%

)


Change in PET-MTV based on Pre-RT Change in CT-GTV based on Pre-RT

0

25

50

75

100

125

150

175

200

225

250


CT

-GT

V (

%)

During-RT PET-CT adapted composite plan: 17.2% lung NTCP~ 86 Gy to during-RT PET-PTV

(102 ED2 lung, ~92 Gy ED2 tumor, ~120 Gy BED for a/b=10).

Pre-RT PET-CT based plan: 17.2% lung NTCP~ 70 Gy

9.8% NTCP ~ 50 Gy

Pre-RT

During-RT

RTOG 0617 (CALGB, NCCTG)

Phase III Trial of Standard-Dose (60 Gy) Versus High-Dose

(74 Gy) Conformal RT w Concurrent & Consolidation Cb/P

in Stage III NSCLC

Primary Endpoint – Survival (n=512)

Stage IIIA/B

PS 0-1

FEV1 ≥1.5L; V20 <37%

No Supraclav LNs

PET recommended

R

A

N

D

O

M

I

Z

E

Concurrent ChemoRT Paclitaxel 45 mg/m2 Carboplatin AUC 2 Weekly x7

RT 60 Gy (2 Gy/d)

+ Cetuximab

Concurrent ChemoRT Paclitaxel 45 mg/m2 Carboplatin AUC 2 Weekly x7

RT 74 Gy (2 Gy/d)

+ Cetuximab

Consolidation Paclitaxel 200mg/m2 Carboplatin AUC 6 q3wks x2 cycles

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Research RFP for RTOG 0617

RTOG 0617

512 Pts Enrolled

Banked Specimens on 50%

Formal RFP for Translational Proposals

IALSC and ASTRO broadcast

25 Applicants

External Peer Review Ongoing

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RTOG Lung Committee Future

NRG Oncology

Will Have 7 Disease Site Committees

Lung Cancer Committee will be One

HQ in Philadelphia

Lung Cancer Biobanking at UCSF

Seeking Links with SPORES/P30/P01’s

rtog lung cancer committee 2012 clinical trial...

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