A Phase II Randomized Trial of Paclitaxel, Carboplatin, Bevacizumab With or Without IMC-A12 in Patients With Advanced Non-squamous, Non-small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Large Cell Lung Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 175
- Locations
- 164
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
This randomized phase II trial studies how well carboplatin, paclitaxel, and bevacizumab (CPB) work when given with or without cixutumumab in treating patients with non-small cell lung cancer that is stage IV or has come back (recurrent). 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, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Other types of monoclonal antibodies, such as cixutumumab, may find tumor cells and help kill them. It is not yet known whether giving more than one drug (combination chemotherapy) together with bevacizumab is more effective when given with or without cixutumumab in treating patients with non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the progression-free survival with the combination of carboplatin, paclitaxel, and bevacizumab, and +/- IMC-A12 (cixutumumab) in patients with advanced, non-squamous, non-small cell lung cancer. SECONDARY OBJECTIVES: I. To evaluate overall survival and response rate of the above combination in patients with non-squamous, advanced non-small cell lung cancer. II. To evaluate the toxicities of the above combination in patients with non-squamous advanced non-small cell lung cancer. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A (CPB): Patients receive carboplatin intravenously (IV) over 30 minutes, paclitaxel IV over 3 hours, and bevacizumab IV over 30-90 minutes on day 1. ARM B (CPB+cixutumumab): Patients receive carboplatin, paclitaxel, and bevacizumab as in Arm A. Patients also receive cixutumumab (IMC-A12) IV over 1 hour on days 1, 8, and 15. In both arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab and cixutumumab may continue in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed with non-squamous, non-small cell lung cancer (NSCLC)
- •Advanced NSCLC defined as either recurrent disease after prior radiation or surgery or stage IV (M1a or M1b) based on the TNM staging system (American Joint Committee on Cancer \[AJCC\] 2009)
- •Measurable disease as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). All sites of disease (of target and non-target disease sites) must be obtained within 4 weeks prior to randomization
- •A head computed tomography (CT) or magnetic resonance imaging (MRI) required within 4 weeks prior to randomization
- •Prior radiation therapy (RT) is allowed if it has been completed 3 weeks prior to randomization and patient has recovered from any adverse events related to RT
- •Brain metastases are allowed, provided they have been treated with surgery and/or radiotherapy, the patient is neurologically stable, and repeat brain imaging shows no progression in the brain; at least 6 weeks should have elapsed from the time of craniotomy and at least 4 weeks from radiotherapy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Absolute neutrophil count (ANC) ≥ 1500/mm³
- •Platelet count ≥ 100,000/mm³
- •Total bilirubin within institutional upper limit of normal (ULN)
Exclusion Criteria
- •Prior chemotherapy or biologic/molecular targeted therapy for advanced NSCLC. Prior chemotherapy and/or biological/molecular targeted therapy as part of initial potentially curative therapy (one regimen of induction and/or adjuvant and/or concurrent chemoradiotherapy) was allowed provided it had been completed 1 year or more prior to randomization
- •Prior treatment with IMC-A12 or another insulin-like growth factor 1 receptor (IGF-1R) inhibitor
- •Patients on therapeutic anticoagulation; patient's international normalized ratio (INR) must be ≤ 1.5 or partial thromboplastin time (PTT) ≤ upper limits of normal within 2 weeks prior to randomization to be eligible; prophylactic anticoagulation of venous access devices is allowed provided the above criteria have been met
- •Prior allergic reaction to compounds of chemical or biologic composition similar to those of IMC-A12
- •Hypersensitivity to any component of bevacizumab
- •Poorly controlled diabetes mellitus
- •History of other invasive malignancies unless there is no active disease and all treatment has been completed ≥ 3 years prior to randomization; patients with history of in-situ malignancies and curatively resected nonmelanomatous skin cancer are eligible
- •History of thrombotic or hemorrhagic disorders
- •History of bleeding diathesis or coagulopathy
- •≥ grade 2 bleeding or any bleeding requiring intervention within 4 weeks prior to randomization
Arms & Interventions
Arm A (CPB)
Patients receive carboplatin intravenously (IV) over 30 minutes, paclitaxel IV over 3 hours, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab may continue in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Arm A (CPB)
Patients receive carboplatin intravenously (IV) over 30 minutes, paclitaxel IV over 3 hours, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab may continue in the absence of disease progression or unacceptable toxicity.
Intervention: Carboplatin
Arm A (CPB)
Patients receive carboplatin intravenously (IV) over 30 minutes, paclitaxel IV over 3 hours, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab may continue in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Arm B (CPB+cixutumumab)
Patients receive carboplatin, paclitaxel, and bevacizumab as in Arm A. Patients also receive cixutumumab (IMC-A12) IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab and cixutumumab may continue in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Arm B (CPB+cixutumumab)
Patients receive carboplatin, paclitaxel, and bevacizumab as in Arm A. Patients also receive cixutumumab (IMC-A12) IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab and cixutumumab may continue in the absence of disease progression or unacceptable toxicity.
Intervention: Carboplatin
Arm B (CPB+cixutumumab)
Patients receive carboplatin, paclitaxel, and bevacizumab as in Arm A. Patients also receive cixutumumab (IMC-A12) IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab and cixutumumab may continue in the absence of disease progression or unacceptable toxicity.
Intervention: Cixutumumab
Arm B (CPB+cixutumumab)
Patients receive carboplatin, paclitaxel, and bevacizumab as in Arm A. Patients also receive cixutumumab (IMC-A12) IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab and cixutumumab may continue in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; up to 5 years
Progression-free survival was defined as the time from randomization to progression or death without documentation of progression. For cases without progression, follow-up was censored at the date of last disease assessment without progression, unless death occurs within 3 months following the date last known progression-free, in which case the death was counted as a failure. Progression was evaluated using RECIST 1.1 criteria and defined as: 1. At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. OR 2. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Secondary Outcomes
- Proportion of Patients With Objective Response(Assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry; up to 5 years)
- Overall Survival (OS)(Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; up to 5 years)