A Phase II First-Line Study of a Combination of Pemetrexed, Carboplatin and Bevacizumab in Advanced Nonsquamous NSCLC Evaluating Efficacy and Tolerability in Elderly Patients (Age ≥ 70 Yrs) With Good Performance Status (PS < 2)
Overview
- Phase
- Phase 2
- Intervention
- bevacizumab
- Conditions
- Lung Cancer
- Sponsor
- Alliance for Clinical Trials in Oncology
- Enrollment
- 65
- Locations
- 215
- Primary Endpoint
- Progression-free Survival at 6 Months
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving pemetrexed together with carboplatin and bevacizumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving pemetrexed together with carboplatin and bevacizumab works as first-line therapy in treating older patients with stage IIIB or stage IV non-small cell lung cancer.
Detailed Description
OBJECTIVES: Primary * To estimate the progression-free survival at 6 months in elderly patients with advanced nonsquamous cell non-small cell lung cancer treated with pemetrexed disodium, carboplatin, and bevacizumab as first-line therapy. Secondary * To assess the adverse events profile and safety of this regimen in these patients. * To estimate the confirmed antitumor response rate, as defined by RECIST criteria, and the overall survival of these patients. * To compare the quality of life (QOL) of patients treated with this regimen vs the QOL of younger patients. * To correlate QOL with toxicities, as defined by NCI CTCAE v3.0 criteria. Tertiary * To evaluate polymorphisms in the genes that encode proteins involved in the cellular transport, activation, and cytotoxic activity of pemetrexed disodium and evaluate their relationship with treatment toxicity/efficacy and patient QOL. * To evaluate polymorphisms in the genes involved in blood pressure regulation and their relationship with susceptibility to hypertension induced by anti-VEGF therapy. OUTLINE: This is a multicenter study. Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response after 6 courses may continue to receive pemetrexed disodium and bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity. Tissue and blood samples are collected at baseline for pharmacogenetic analysis. Blood samples are used to evaluate functionally relevant polymorphisms in the genes that encode proteins involved in the transport and activation of pemetrexed disodium and in the genes that encode proteins involved in susceptibility to hypertension induced by bevacizumab. Tissue samples are used to evaluate expression and polymorphisms in pemetrexed disodium target genes (TS, DHFR, and GARFT). Quality of life is assessed at baseline and periodically during study. After completion of study therapy, patients are followed periodically for up to 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
pemetrexed + carboplatin + bevacizumab
Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response after 6 courses may continue to receive pemetrexed disodium and bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: bevacizumab
pemetrexed + carboplatin + bevacizumab
Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response after 6 courses may continue to receive pemetrexed disodium and bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: carboplatin
pemetrexed + carboplatin + bevacizumab
Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response after 6 courses may continue to receive pemetrexed disodium and bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: pemetrexed disodium
Outcomes
Primary Outcomes
Progression-free Survival at 6 Months
Time Frame: 6 months
Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients). A patient is classified as a success if alive and progression-free at 6 months.
Secondary Outcomes
- Proportion of Confirmed Tumor Response Defined as an Objective Status of Complete Response or Partial Response on Two Consecutive Evaluations(Duration of study until progression (up to 5 years))
- Duration of Response(Up to 5 years)
- Number of Grade 3 or Higher Adverse Events Occurring in >=10% of Patients(Up to 2.5 years)
- Time to Treatment Failure(Up to 5 years)
- Progression-free Survival(Up to 5 years)
- Overall Survival(Up to 5 years)
- Change From Baseline to Cycle 3 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale(Baseline and Cycle 3)
- Change From Baseline to Cycle 5 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale(Baseline and Cycle 5)
- Change From Baseline to Cycle 3 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA)(Baseline and Cycle 3)
- Change From Baseline to Cycle 5 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA)(Baseline and Cycle 5)
- Change From Baseline to Cycle 3 in Fatigue Assessed by Treatment-specific Adverse Events Scale(Baseline and Cycle 3)
- Change From Baseline to Cycle 5 in Fatigue Assessed by Treatment-specific Adverse Events Scale(Baseline and Cycle 5)
- Change From Baseline to Cycle 3 in Neuropathy Assessed by Treatment-specific Adverse Events Scale(Baseline and Cycle 3)
- Change From Baseline to Cycle 5 in Neuropathy Assessed by Treatment-specific Adverse Events Scale(Baseline and Cycle 5)
- Change From Baseline to Cycle 3 in Nausea Assessed by Treatment-specific Adverse Events Scale(Baseline and Cycle 3)
- Change From Baseline to Cycle 5 in Nausea Assessed by Treatment-specific Adverse Events Scale(Baseline and Cycle 5)