Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Vinorelbine Plus Cisplatin or No Further Therapy in Treating Patients With Non-small Cell Lung Cancer That Has Been Surgically Removed

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	CAN-NCIC-BR10 CLB-9795, E-JBR10, SWOG-JBR10, GW-565/040, NCI-V94-0492, NCT00002583, BR10, JBR10

Objectives

I. Compare the duration of overall and disease-free survival in patients with 
completely resected non-small cell lung cancer (NSCLC) randomized to adjuvant 
chemotherapy with vinorelbine and cisplatin versus observation only.

II. Confirm the prognostic significance of ras mutations when present in the 
primary tumor.

III. Provide a comprehensive tumor bank linked to a clinical database for the 
further study of molecular markers in resected NSCLC.

IV. Measure and compare the health-related quality of life of patients on both 
treatment arms.

V. Evaluate any toxicity related to this treatment regimen.

Entry Criteria

Disease Characteristics:

Histologically confirmed primary non-small cell lung cancer that is completely
resected
 No mixed small and non-small cell histologies

 Pathologic T2 N0 or T1-2 N1
 T1 N1 and T2 N1 only for CALGB institutions

 Removal of all gross disease with negative resection margins by lobectomy,
  sleeve resection, bilobectomy, or pneumonectomy (based on intraoperative
  findings)
   No segmentectomy or wedge resection

 Complete mediastinal lymph node resection or sampling required at primary
 tumor resection, with minimum levels of nodal sampling as follows:
  Primary in right upper lobe - levels 4, 7, 10
  Primary in right middle lobe - levels 4, 7, 10
  Primary in right lower lobe - levels 4, 7, 9, 10
  Primary in left upper lobe - levels 5, 6, 7, 10
  Primary in left lower lobe - levels 7, 9, 10

 If complete mediastinal lymph node resection has not been undertaken, any
  mediastinal lymph node which measured 1.5 cm or more on presurgical CT scan
  must have been biopsied and found to be free of metastatic involvement
   
 Disease at nodal station 10 (tracheobronchial angle) is considered N2
  disease for this trial and is not eligible

No more than one discrete primary tumor

No bronchoalveolar carcinoma with lobar or multilobar involvement
 Discrete solitary radiological mass or nodule eligible

Snap frozen fresh primary tumor tissue must be submitted to Lung Cancer Tumor
Bank within 14 days after surgery by selected Canadian centers
 Others to submit representative paraffin block within 2 months of surgery

Prior/Concurrent Therapy:

Complete resection required
 Randomization between 28 and 40 days after surgery required

Patient Characteristics:

Age:
 18 and over (lower age limit determined by individual center)

Performance status:
 ECOG 0 or 1

Life expectancy:
 Not specified

Hematopoietic:
 Absolute granulocyte count greater than 2,000/mm3
 Platelet count greater than 100,000/mm3
 Hemoglobin greater than 10.0 g/dL

Hepatic:
 Bilirubin no greater than 1.25 times normal
 AST/ALT no greater than 1.25 times normal
 Alkaline phosphatase no greater than 1.25 times normal

Renal:
 Creatinine no greater than 1.7 mg/dL

Cardiovascular:
 No history of congestive heart failure or other cardiac abnormality that may
  preclude hydration necessary for cisplatin administration

Other:
 No active pathologic condition that would preclude study
 No active uncontrolled infection
 No history of psychiatric or neurologic disorder that would preclude study
 No prior breast cancer, melanoma, or hypernephroma
 No other malignancy within the past 5 years except adequately treated
  nonmelanomatous skin cancer or carcinoma in situ of the cervix
 Not pregnant or nursing 
 Fertile patients must use effective contraception
 Ability to tolerate treatment (based on consultation between the thoracic
  surgeon and a medical oncologist or hematologist) and available for
  follow-up

Expected Enrollment

A total of 450 patients will be accrued for this study within 6.75 years.

Outline

This is a randomized study.  Patients are stratified according to 
participating institution, nodal status (N0 vs N1), and ras mutation status of 
primary tumor (absent vs present vs unknown).  Patients are randomized to one 
of two treatment arms.

Arm I:  Patients are evaluated at 3 and 6 months after randomization.

Arm II:  Patients receive vinorelbine IV over 6-10 minutes weekly for 16 
weeks.  Patients also receive cisplatin IV on days 1 and 8 every 4 weeks for a 
total of 4 courses.  Treatment continues in the absence of disease progression 
or unacceptable toxicity.

Quality of life is assessed at Canadian centers. Quality of life assessments 
are optional for ECOG and SWOG centers.

Patients are followed every 3 months for 2 years and then every 6 months 
thereafter.

Bezjak A, Lee CW, Ding K, et al.: Quality-of-life outcomes for adjuvant chemotherapy in early-stage non-small-cell lung cancer: results from a randomized trial, JBR.10. J Clin Oncol 26 (31): 5052-9, 2008.[PUBMED Abstract]

Jang RW, Le Maître A, Ding K, et al.: A Q-TWiST analysis of adjuvant chemotherapy in non-small cell lung cancer (NSCLC) in the NCIC CTG JBR.10 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-6535, 2008.

Tsao MS, Zhu C, Ding K, et al.: A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients. [Abstract] J Clin Oncol 26 (Suppl 15): A-7510, 2008.

Bezjak A, Lee CW, Ding K, et al.: Quality of life (QOL) impact of adjuvant chemotherapy for early stage non-small cell lung cancer (NSCLC): final analysis of JBR.10 randomized trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-7585, 405s, 2007.

Gauthier I, Ding K, Winton T, et al.: Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: the JBR.10 trial experience. Lung Cancer 55 (3): 357-63, 2007.[PUBMED Abstract]

Pepe C, Hasan B, Winton TL, et al.: Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10. J Clin Oncol 25 (12): 1553-61, 2007.[PUBMED Abstract]

Sève P, Lai R, Ding K, et al.: Class III beta-tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of NCIC JBR.10. Clin Cancer Res 13 (3): 994-9, 2007.[PUBMED Abstract]

Tsao MS, Aviel-Ronen S, Ding K, et al.: P53 protein over-expression but not p53 gene mutation is a poor prognostic marker and a predictive marker for survival benefit from adjuvant chemotherapy in non-small cell lung cancer (NSCLC) in the JBR.10 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-7577, 403s, 2007.

Pepe C, Hasan B, Winton T, et al.: Adjuvant chemotherapy in elderly patients: an analysis of National Cancer Institute of Canada Clinical Trials Group and Intergroup BR.10. [Abstract] J Clin Oncol 24 (Suppl 18): A-7009, 2006.

Reiman T, Lai R, Ding K, et al.: Class III beta tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study JBR.10. [Abstract] J Clin Oncol 24 (Suppl 18): A-7051, 376s, 2006.

Alam N, Shepherd FA, Winton T, et al.: Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature. Lung Cancer 47 (3): 385-94, 2005.[PUBMED Abstract]

Gauthier I, Ding K, Winton T, et al.: Impact of hemoglobin (Hb) on outcomes of adjuvant chemotherapy (ACT) with cisplatin/vinorelbine in patients (pts) with completely resected non small cell lung cancer (NSCLC) in JBR.10. [Abstract] J Clin Oncol 23 (Suppl 16): A-7200, 670s, 2005.

Winton T, Livingston R, Johnson D, et al.: Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 352 (25): 2589-97, 2005.[PUBMED Abstract]

Winton TL, Livingston R, Johnson D, et al.: A prospective randomised trial of adjuvant vinorelbine (VIN) and cisplatin (CIS) in completely resected stage 1B and II non small cell lung cancer (NSCLC) Intergroup JBR.10. [Abstract] J Clin Oncol 22 (Suppl 14): A-7018, 621s, 2004.

Alam N, Shepherd F, Winton T, et al.: Compliance with adjuvant chemotherapy (ACT) in non-small lung cancer (NSCLC): NCIC-CTG BR.10/JBR.10. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2547, 633, 2003.

Beziak A, Winton T, Ding K, et al.: Quality of life in a trial of adjuvant chemotherapy for early stage completely resected non-small cell lung cancer (NCIC CTG BR.10). [Abstract] Lung Cancer 41 (Suppl 2): S20, 2003.

Asmis TR, Ding K, Seymour L, et al.: Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: a review of National Cancer Institute of Canada Clinical Trials Group trials. J Clin Oncol 26 (1): 54-9, 2008.[PUBMED Abstract]

Wheatley-Price P, Le Maître A, Ding K, et al.: The influence of sex on efficacy, toxicity and delivery of treatment in National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) non-small cell lung cancer (NSCLC) chemotherapy trials. [Abstract] J Clin Oncol 26 (Suppl 15): A-8054, 2008.

Hicks L, Cheung M, Hasan B, et al.: Venous thromboembolism and non-small cell lung cancer: a pooled analysis of National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials. [Abstract] Blood 110 (11): A-3995, 2007.

Kassam F, Shepherd FA, Johnston M, et al.: Referral patterns for adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. J Thorac Oncol 2 (1): 39-43, 2007.[PUBMED Abstract]

Ng R, Hasan B, Mittmann N, et al.: Economic analysis of NCIC CTG JBR.10: a randomized trial of adjuvant vinorelbine plus cisplatin compared with observation in early stage non-small-cell lung cancer--a report of the Working Group on Economic Analysis, and the Lung Disease Site Group, National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25 (16): 2256-61, 2007.[PUBMED Abstract]

Hotta K, Matsuo K, Kiura K, et al.: Advances in our understanding of postoperative adjuvant chemotherapy in resectable non-small-cell lung cancer. Curr Opin Oncol 18 (2): 144-50, 2006.[PUBMED Abstract]

Pignon JP, Tribodet H, Scagliotti GV, et al.: Lung Adjuvant Cisplatin Evaluation (LACE): a pooled analysis of five randomized clinical trials including 4,584 patients. [Abstract] J Clin Oncol 24 (Suppl 18): A-7008, 2006.

Wakelee HA, Schiller JH, Gandara DR: Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial. Clin Lung Cancer 8 (1): 18-21, 2006.[PUBMED Abstract]

Visbal AL, Leighl NB, Feld R, et al.: Adjuvant Chemotherapy for Early-Stage Non-small Cell Lung Cancer. Chest 128 (4): 2933-43, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Timothy Winton, MD, Protocol chair		Ph: 780-407-3623 Email: twinton@cha.ab.ca

Southwest Oncology Group

Eric Vallieres, MD, FRCSC, Protocol chair(Contact information may not be current)		Ph: 206-543-3093 Email: evallier@u.washington.edu

Eastern Cooperative Oncology Group

Russell DeVore, MD, Protocol chair(Contact information may not be current)		Ph: 615-936-1782; 800-811-8480 Email: russell.devore@mcmail.vanderbilt.edu

Cancer and Leukemia Group B

James Rigas, MD, Protocol chair		Ph: 603-650-6344; 800-639-6918 Email: james.r.rigas@dartmouth.edu

Registry Information
Official Title		A PHASE III PROSPECTIVE RANDOMIZED STUDY OF ADJUVANT CHEMOTHERAPY WITH VINORELBINE AND CISPLATIN IN COMPLETELY RESECTED NON-SMALL CELL LUNG CANCER WITH COMPANION TUMOUR MARKER EVALUATION
Trial Start Date		1994-07-07
Registered in ClinicalTrials.gov		NCT00002583
Date Submitted to PDQ		1994-07-07
Information Last Verified		2008-11-21
NCI Grant/Contract Number		R24-CA77202