Randomized Phase II/III Trial of Paclitaxel Plus Carboplatin With or Without Bevacizumab (NSC #704865) in Patients With Advanced Nonsquamous NSCLC
PRIMARY OBJECTIVES:
I. To assess toxicity and survival in patients with advanced or metastatic (stage IIIB
pleural effusion/IV), nonsquamous histology non-small cell lung cancer (NSCLC) treated with
carboplatin plus paclitaxel +/- bevacizumab. (Phase II) II. To assess response rates and
time to progression in patients with advanced or metastatic (stage IIIB-pleural
effusion/IV), nonsquamous histology NSCLC treated with carboplatin plus paclitaxel +/-
bevacizumab. (Phase II) III. To assess overall survival in patients with advanced or
metastatic (stage IIIB-pleural effusion/IV), nonsquamous histology NSCLC treated with
carboplatin plus paclitaxel +/- bevacizumab. (Phase III) IV. To assess response rates, time
to progression, and toxicity in patients with advanced or metastatic (stage IIIB-pleural
effusion/IV), non-squamous histology NSCLC treated with carboplatin plus paclitaxel +/-
bevacizumab. (Phase III)
SECONDARY OBJECTIVES:
I. To determine if pre-treatment levels of plasma VEGF predict response to chemotherapy with
carboplatin-Taxol with or without anti-VEGF monoclonal antibody (MAb).
II. To determine if pre-treatment plasma VEGF is of prognostic value in advanced NSCLC.
III. To determine whether elevated plasma levels of endothelial cell-specific proteins
(VCAM, E-selectin), reflective of chemotherapy or anti-VEGF induced endothelial damage, are
useful markers in assessing response to carboplatin/Taxol +/- anti-VEGF therapy.
IV. To determine whether pre- and post-treatment plasma levels of basic fibroblast growth
factor (bFGF) is of prognostic value or predictive of response to therapy.
OUTLINE: This is a randomized study. Patients are stratified according to measurable disease
(yes vs no), prior radiotherapy (yes vs no), weight loss (less than 5% vs 5% or more), and
disease stage (IIIB vs IV vs recurrent). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 15-30
minutes on day 1.
ARM II: Patients receive paclitaxel and carboplatin as in arm I followed by bevacizumab IV
over 30-90 minutes on day 1.
Treatment in both arms repeats every 3 weeks for up to 6 courses in the absence of disease
progression or unacceptable toxicity.
After completion of 6 courses, patients in arm II with stable or responding disease continue
to receive bevacizumab only. Treatment repeats every 3 weeks in the absence of disease
progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 842 patients will be accrued for this study.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Survival
Analyses will be based on repeated confidence intervals for the hazard ratio, using O'Brien-Fleming stopping boundaries corresponding to a one-sided, 2.5% overall type I error. The confidence interval will be calculated on the log hazard ratio scale based on the log hazard ratio and variance estimates from the Cox partial likelihood, using the large sample normal approximation, and then the interval will be transformed to the hazard ratio scale.
Up to 5 years
No
Alan Sandler
Principal Investigator
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
NCI-2012-02947
NCT00021060
August 2002
Name | Location |
---|---|
Eastern Cooperative Oncology Group | Boston, Massachusetts 02215 |