Carboplatin, Paclitaxel, and Bevacizumab With or Without Erlotinib Hydrochloride in Treating Non-Smokers With Advanced Non-Small Cell Lung Cancer
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Purpose
This randomized phase II trial is studying how well carboplatin, paclitaxel, and bevacizumab work when given with or without erlotinib hydrochloride in treating non-smokers with advanced non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving combination chemotherapy together with bevacizumab is more effective with or without erlotinib hydrochloride in treating patients with non-small cell lung cancer
| Condition | Intervention | Phase |
|---|---|---|
|
Recurrent Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer |
Drug: erlotinib hydrochloride Drug: paclitaxel Drug: carboplatin Biological: bevacizumab |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | Randomized Double-Blind Placebo Controlled Phase II Trial Evaluating Erlotinib in Non-Smoking Patients With (Bevacizumab-Eligible and Ineligible) Advanced Non-Small Cell Lung Cancer (NSCLC) |
- Progression-free survival (PFS) [ Time Frame: From randomization to progression of disease or death, whichever occurs first, up to 5 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Response rate by RECIST criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- EGFR positivity assessed by FISH [ Time Frame: Baseline ] [ Designated as safety issue: No ]
| Enrollment: | 189 |
| Study Start Date: | January 2010 |
| Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Arm I
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes (with or without bevacizumab IV over 30-90 minutes) on day 1. Patients also receive an oral placebo once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive placebo (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.
|
Drug: paclitaxel
Given IV
Other Names:
Drug: carboplatin
Given IV
Other Names:
Biological: bevacizumab
Given IV
Other Names:
|
|
Experimental: Arm II
Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in arm I. Patients also receive oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive erlotinib hydrochloride (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.
|
Drug: erlotinib hydrochloride
Given orally
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Drug: carboplatin
Given IV
Other Names:
Biological: bevacizumab
Given IV
Other Names:
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the progression-free survival (PFS) of non-smokers with advanced non-small cell lung cancer randomized to receive treatment with standard care (carboplatin and paclitaxel with or without bevacizumab) or standard care in combination with erlotinib hydrochloride.
SECONDARY OBJECTIVES:
I. To evaluate the overall survival of these patients. II. To evaluate the response rate in these patients. III. To evaluate the relative toxicity of these regimens in these patients. IV. To determine the frequency of EGFR and Kras mutations in these patients and correlate mutation status with response rate and PFS.
V. To obtain blood and tissue specimens for further marker-based exploratory analyses regarding EGFR inhibitors.
VI. To evaluate EGFR positivity by FISH as a predictor of improved PFS in patients treated with erlotinib hydrochloride.
OUTLINE: This is a multicenter study. Patients are stratified according to gender and eligibility for bevacizumab therapy (ineligible vs eligible and willing to receive bevacizumab vs eligible and not willing to receive bevacizumab). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes (with or without bevacizumab IV over 30-90 minutes) on day 1. Patients also receive an oral placebo once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive placebo (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in arm I. Patients also receive oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive erlotinib hydrochloride (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.
Blood and tissue samples are collected for correlative laboratory studies.
After completion of study treatment, patients are followed up periodically for 5 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Histologically or cytologically confirmed non-small cell lung cancer, meeting one of the following criteria:
- Stage IIIB disease with pleural or pericardial effusion or multifocal pleural involvement
- Stage IV disease
- Recurrent disease after prior curative resection or definitive radiotherapy
- Non-squamous cell histology (for patients planning to receive bevacizumab)
- Has smoked ≤ 100 cigarettes in a lifetime
- Measurable disease as defined by RECIST criteria
- No history of untreated brain metastases
- ECOG performance status 0-1
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 mg/dL
- SGOT and SGPT ≤ 3 times upper limit of normal
- Creatinine ≤ 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No clinically significant ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
- No other active, invasive malignancies requiring therapy
Patients planning to receive bevacizumab must meet the following additional criteria:
- INR ≤ 3 within the past 4 weeks
- Urine protein ≤ 1+ by urine dipstick within the past 4 weeks OR urine protein:creatinine ratio < 1.0
- No antecedent hemoptysis
- No history of thrombotic or hemorrhagic disorders
- History of hypertension allowed provided it is well controlled (i.e., BP ≤ 150/90 mm Hg) and patient has been on a stable regimen of antihypertensive therapy within the past 4 weeks
- History of myocardial infarction or other evidence of arterial thrombotic disease (angina) allowed provided there is no evidence of active disease for ≥ 6 months
- No serious non-healing wound, ulcer, or bone fracture within the past 4 weeks
- No abdominal fistula, gastrointestinal perforation,or intra-abdominal abscess within the past 6 months
- No significant vascular disease (e.g., aortic aneurysm,requires surgical repair, or recent peripheral arterial thrombosis) within the past 6 months
No clinically significant cardiovascular disease, including any of the following:
- Cerebrovascular accident within the past 6 months
- New York Heart Association class II-IV heart failure
- Serious and inadequately controlled cardiac arrhythmia
- Clinically significant peripheral vascular disease (symptomatic with intermittent claudications or < 6 months since bypass surgery)
- No prior chemotherapy for lung cancer
- More than 3 years since prior chemotherapy for an unrelated condition
- At least 2 weeks since prior radiotherapy and recovered (alopecia and grade 1 neuropathy allowed)
- No prior irradiation to the only site of measurable disease, unless that site has had subsequent evidence of pathology or radiologic progression
- More than 28 days since prior major surgical procedure (for patients planning to receive bevacizumab)
- Concurrent stable doses of therapeutic anticoagulation or prophylactic anticoagulation for venous access devices allowed (for patients planning to receive bevacizumab)
Contacts and Locations
Show 108 Study Locations| Principal Investigator: | Corey Langer | Eastern Cooperative Oncology Group |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00976677 History of Changes |
| Other Study ID Numbers: | NCI-2011-01967, E2508, U10CA021115, CDR0000654212 |
| Study First Received: | September 11, 2009 |
| Last Updated: | January 15, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Antibodies Antibodies, Monoclonal Bevacizumab Carboplatin Paclitaxel |
Erlotinib Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013