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Randomized Phase II/III Trial of Paclitaxel Plus Carboplatin With or Without Bevacizumab (NSC #704865) in Patients With Advanced Nonsquamous NSCLC


Phase 2/Phase 3
18 Years
N/A
Not Enrolling
Both
Adenocarcinoma of the Lung, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

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Trial Information

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.


Inclusion Criteria:



- Patients must have histologically or cytologically confirmed non-small cell lung
cancer EXCEPT squamous cell carcinoma; mixed tumors will be categorized by the
predominant cell type unless small cell elements are present in which case the
patient is ineligible; cytologic or histologic elements can be established on
metastatic tumor aspirates or biopsy

- Patients must have advanced NSCLC (stage IIIB with malignant pleural effusion or
stage IV or recurrent disease)

- Patients must have measurable or non-measurable disease

- ECOG performance status 0 or 1

- Patients must not have known central nervous system (CNS) metastases; a head CT is
required within 4 weeks prior to study entry; (MRIs are also acceptable)

- Patients must not have received prior systemic chemotherapy at any time

- ANC >= 1500/mm^3

- Platelets >= 100,000/mm^3

- Total bilirubin =< 1.5 mg/dl

- Transaminases =< 5 x ULN

- Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN)

- Urine dipstick for proteinuria of less than 1+ (i.e., either 0 or trace); if urine
dipstick is >= 1+ then a 24 hour urine for protein must demonstrate < 500 mg of
protein in 24 hours to allow participation in the study; note: urinalysis is also
acceptable

- Patients must have INR =< 1.5 and a PTT no greater than upper limits of normal within
1 week prior to randomization

- Pregnant and lactating women are excluded from the study

- Women of childbearing potential and sexually active males must agree to use an
accepted and effective method of contraception (hormonal or barrier methods,
abstinence) prior to study entry and for the duration of the study

- Patients must not have had immuno, hormonal or radiation therapy within 3 weeks prior
to entering the study; those who have not recovered from adverse events due to agents
administered more than 3 weeks earlier are ineligible

- Patients must not have ongoing or active infection, symptomatic congestive heart
failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements

- Patients must have no history of thrombotic or hemorrhagic disorders

- Patients with history of hypertension must be well-controlled (< 150/100) on a stable
regimen of anti-hypertensive therapy

- Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or
nonsteroidal anti-inflammatory agents known to inhibit platelet function; treatment
with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or
cilostazol (Pletal) is also not allowed

- Patients must not have serious non-healing wound ulcer, or bone fracture, or major
surgical procedure within 21 days prior to starting treatment

- Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation of
venous access devices is allowed; caution should be taken on treating patients with
low dose heparin or low molecular weight heparin for DVT prophylaxis during treatment
with bevacizumab as there may be an increased risk of bleeding

- Patients with a history of gross hemoptysis (defined as bright red blood of a 1/2
teaspoon or more) will be excluded from this trial

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Survival

Outcome Description:

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.

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Alan Sandler

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02947

NCT ID:

NCT00021060

Start Date:

August 2002

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Lung
  • Bronchoalveolar Cell Lung Cancer
  • Large Cell Lung Cancer
  • Recurrent Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Adenocarcinoma, Bronchiolo-Alveolar
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Eastern Cooperative Oncology GroupBoston, Massachusetts  02215