Combination Chemotherapy With or Without Tirapazamine in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of carboplatin plus paclitaxel with or without tirapazamine in treating patients who have stage IIIB or stage IV non-small cell lung cancer.

Timeline

Start

2000-11

Primary completion

—

Completion

2006-04

Outcome

Missed primary endpoint

paper The addition of tirapazamine to paclitaxel and carboplatin does not result in improved survival in advanced NSCLC compared with paclitaxel and carboplatin alone PMID 16361616 ↗

paper The trial was closed early after an interim analysis demonstrated that the projected 37.5% improvement in survival (8 v 11 months median survival) in arm 1 was unachievable (P = .003). PMID 16361616 ↗

Publications

• Background Lara PN Jr, Redman MW, Kelly K, Edelman MJ, Williamson SK, Crowley JJ, Gandara DR; Southwest Oncology Group. Disease control rate at 8 weeks predicts clinical benefit in advanced non-small-cell lung cancer: results from Southwest Oncology Group randomized trials. J Clin Oncol. 2008 Jan 20;26(3):463-7. doi: 10.1200/JCO.2007.13.0344.
• Background Gandara DR, Kawaguchi T, Crowley JJ, et al.: Pharmacogenomic (PG) analysis of Japan-SWOG common arm study in advanced stage non-small cell lung cancer (NSCLC): a model for testing population-related pharmacogenomics. [Abstract] J Clin Oncol 25 (Suppl 18): A-7500, 2007.
• Background Lara PN Jr, Redman MW, Kelly K, et al.: Alternative measures predicting clinical benefit in advanced non-small cell lung cancer (NSCLC) from Southwest Oncology Group (SWOG) randomized trials: implications for clinical trial design. [Abstract] J Clin Oncol 24 (Suppl 18): A-7006, 365s, 2006.
• Results Mack PC, Redman MW, Chansky K, Williamson SK, Farneth NC, Lara PN Jr, Franklin WA, Le QT, Crowley JJ, Gandara DR; SWOG. Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J Clin Oncol. 2008 Oct 10;26(29):4771-6. doi: 10.1200/JCO.2008.17.0662. Epub 2008 Sep 8.
• Results Mack PC, Redman MW, Chansky K, et al.: Elevated osteopontin (OPN) plasma levels are highly prognostic in advanced non-small cell lung cancer (NSCLC): analysis of SWOG S0003. [Abstract] J Clin Oncol 24 (Suppl 18): A-7198, 413s, 2006.
• Results Williamson SK, Crowley JJ, Lara PN Jr, McCoy J, Lau DH, Tucker RW, Mills GM, Gandara DR; Southwest Oncology Group Trial S0003. Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003. J Clin Oncol. 2005 Dec 20;23(36):9097-104. doi: 10.1200/JCO.2005.01.3771.
• Results Kimura T, Holland WS, Kawaguchi T, Williamson SK, Chansky K, Crowley JJ, Doroshow JH, Lenz HJ, Gandara DR, Gumerlock PH. Mutant DNA in plasma of lung cancer patients: potential for monitoring response to therapy. Ann N Y Acad Sci. 2004 Jun;1022:55-60. doi: 10.1196/annals.1318.010.
• Results Williamson SK, Crowley JJ, Lara PN, et al.: S0003: paclitaxel/carboplatin (PC) versus PC + tirapazamine (PCT) in advanced non-small cell lung cancer (NSCLC). A phase III Southwest Oncology Group (SWOG) trial. [Abstract] Lung Cancer 41 (Suppl 2): A-O-89, S29, 2003.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	tirapazamine	Small molecule	260 mg/m2	Intravenous
Subject	tirapazamine	Small molecule	330 mg/m2	Intravenous
Background	Carboplatin	Small molecule	—	Intravenous
Background	Paclitaxel	Small molecule	225 mg/m2	Intravenous

Indications