Paclitaxel + Carboplatin With/ut BMS-275291 in Advanced or Metastatic Non-small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether paclitaxel and carboplatin are more effective with or without BMS-275291 for non-small cell lung cancer. PURPOSE: Randomized phase II/III trial to compare the effectiveness of paclitaxel and carboplatin with or without BMS-275291 in treating patients who have advanced or metastatic non-small cell lung cancer.

Sex

All

Minimum age

18 Years

Maximum age

120 Years

DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed stage IIIB or IV non-small cell lung cancer (NSCLC)

  * Local or metastatic failure after surgery and/or radiotherapy allowed
* Phase II only:

  * At least one measurable lesion

    * At least 20 mm by conventional techniques OR 10 mm by spiral CT scan
* No known CNS metastases unless asymptomatic and at least 4 weeks since prior corticosteroid therapy

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 12 weeks

Hematopoietic:

* Absolute granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* ALT no greater than 2 times ULN (5 times ULN for liver metastases)

Renal:

* Creatinine no greater than 1.5 times ULN

Cardiovascular:

* No significant cardiac disease
* No uncontrolled high blood pressure, unstable angina, congestive heart failure, second or third degree atrioventricular conduction defects, or ventricular arrhythmias requiring medication
* No myocardial infarction within the past year

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior allergic reaction to drugs containing Cremophor EL
* No serious active infection or other underlying medical condition that would preclude study participation
* No peripheral neuropathy
* No condition (e.g., psychological, geographical) that would preclude study participation
* No prior breast cancer or melanoma
* No other prior malignancy within the past 5 years except carcinoma in situ, basal cell or squamous cell skin cancer, or other cancer that has been curatively treated surgically

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior immunotherapy
* No prior biological response modifiers
* No other concurrent biologic therapy or immunotherapy

Chemotherapy:

* No prior antineoplastic chemotherapy, including intrapleural chemotherapy

Endocrine therapy:

* See Disease Characteristics

Radiotherapy:

* See Disease Characteristics
* No prior radiotherapy to study lesion (unless evidence of disease progression) or to 30% or greater of marrow bearing bones
* At least 1 week since prior radiotherapy and recovered
* No concurrent radiotherapy

Surgery:

* See Disease Characteristics
* At least 2 weeks since prior major surgery
* No concurrent surgery

Other:

* At least 2 weeks since prior investigational drugs
* No other concurrent cytotoxic anticancer therapy
* No other investigational drugs during and for 30 days after study

• BACKGROUNDBradbury PA, Twumasi-Ankrah P, Ding K, et al.: The impact of brain metastases on overall survival (OS) in National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) clinical trials (CT) in advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 27 (Suppl 15): A-8075, 2009.
• BACKGROUNDAsmis TR, Ding K, Seymour L, Shepherd FA, Leighl NB, Winton TL, Whitehead M, Spaans JN, Graham BC, Goss GD; National Cancer Institute of Canada Clinical Trials Group. 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. 2008 Jan 1;26(1):54-9. doi: 10.1200/JCO.2007.12.8322. PMID 18165640
• BACKGROUNDWheatley-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.
• BACKGROUNDHicks LK, Cheung MC, Ding K, Hasan B, Seymour L, Le Maitre A, Leighl NB, Shepherd FA. Venous thromboembolism and nonsmall cell lung cancer: a pooled analysis of National Cancer Institute of Canada Clinical Trials Group trials. Cancer. 2009 Dec 1;115(23):5516-25. doi: 10.1002/cncr.24596. PMID 19711465
• BACKGROUNDDouillard JY, Peschel C, Shepherd F, Paz-Ares L, Arnold A, Davis M, Tonato M, Smylie M, Tu D, Voi M, Humphrey J, Ottaway J, Young K, Vreckem AV, Seymour L. Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer. Lung Cancer. 2004 Dec;46(3):361-8. doi: 10.1016/j.lungcan.2004.05.009. PMID 15541822
• RESULTLeighl NB, Paz-Ares L, Douillard JY, Peschel C, Arnold A, Depierre A, Santoro A, Betticher DC, Gatzemeier U, Jassem J, Crawford J, Tu D, Bezjak A, Humphrey JS, Voi M, Galbraith S, Hann K, Seymour L, Shepherd FA. Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18. J Clin Oncol. 2005 Apr 20;23(12):2831-9. doi: 10.1200/JCO.2005.04.044.