RATIONALE: Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether cediranib is more effective than a placebo when given together with paclitaxel and carboplatin in treating patients with non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying how well cediranib works when given together with paclitaxel and carboplatin in treating patients with stage IIIB or stage IV non-small cell lung cancer.
OBJECTIVES: Primary * To compare overall survival of patients with stage IIIB-IV non-small cell lung cancer treated with cediranib vs placebo administered in combination with paclitaxel and carboplatin. Secondary * To compare the progression-free survival of patients treated with these regimens. * To compare the objective response rates in patients treated with these regimens. * To estimate time to response and response duration in patients treated with these regimens. * To evaluate the nature, severity, and frequency of toxicities, including hemorrhage and hemoptysis, in patients treated with these regimens. * To compare the pharmacokinetics of paclitaxel between the two arms in a subset of enrolled patients * To compare the quality of life of patients treated with these regimens. * To determine the incremental cost effectiveness and cost utility ratios for these regimens. * To correlate the expression of tissue markers (at diagnosis) with outcomes and response in an exploratory fashion OUTLINE: This is a multicenter study. Patients are stratified by gender, center, disease stage (IIIB vs IV), weight loss (\< 5% vs 5-10% vs unknown), and prior adjuvant chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. * Arm II: Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I. Treatment in both arms repeats every 21 days for 4 to 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, on day 1 of each course, and periodically thereafter. After completion of study therapy, patients are followed every 12 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
306
Instituto Nacional de Cancer (INCA)
Rio de Janeiro, Brazil
Instituto de Cancer Arnaldo Vieira de Carvalho
São Paulo, Brazil
Tom Baker Cancer Centre
Calgary, Alberta, Canada
Cross Cancer Institute
Edmonton, Alberta, Canada
BCCA - Abbotsford Centre
Abbotsford British Columbia, British Columbia, Canada
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, Canada
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada
London Regional Cancer Program
London, Ontario, Canada
...and 9 more locations
Overall Survival
Medians of survival time, and their confidence intervals.
Time frame: at every 3 months visit throughout trial, a median of 13.1 months.
Progression-free Survival
Medians of PFS and their confidence intervals by arm
Time frame: at every 3 months visit throughout trial, a median of 12 months
Objective Tumor Response as Assessed by RECIST Criteria v1.1.
Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression.
Time frame: Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression.
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