Pemetrexed, Carboplatin, and Bevacizumab as First-Line Therapy in Treating Older Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
- Conditions
- Lung Cancer
- Interventions
- Registration Number
- NCT00798603
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 65
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description pemetrexed + carboplatin + bevacizumab 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. pemetrexed + carboplatin + bevacizumab pemetrexed disodium 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. pemetrexed + carboplatin + bevacizumab carboplatin 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.
- Primary Outcome Measures
Name Time Method Progression-free Survival at 6 Months 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 Outcome Measures
Name Time Method 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) Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:
Complete Response (CR): disappearance of all target and non-target lesions and no new lesions.
Partial Response (PR): disappearance of all target lesions, persistence of one or more non-target lesions, and no new lesions; or at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD, no appearance of one/more new lesions, unequivocal progression of existing non-target lesions, and no new lesions.Duration of Response Up to 5 years Duration of response for responders was defined as the time from the date of the first objective status assessment of a confirmed CR or PR to the first date of disease progression. Duration of response will be censored at the date of last post-therapy follow-up visit for responders who have not had disease progression. Duration of response will be calculated for all evaluable patients who have achieved an objective confirmed response.
Number of Grade 3 or Higher Adverse Events Occurring in >=10% of Patients Up to 2.5 years Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death.
Time to Treatment Failure Up to 5 years Time to treatment failure was defined to be the time from date of registration to the date at which the patient is removed from the treatment due to progression, toxicity, refusal or death from any cause.
Progression-free Survival Up to 5 years Progression-free survival was defined as the time from study enrollment to the first date of disease progression or death as a result of any cause, whichever occurs first. Progression-free survival will be censored at the date of the last contact for patients who are still alive and who have not had disease progression.
Overall Survival Up to 5 years Overall survival was defined as the time from study enrollment to the time of death from any cause. Overall survival will be censored at the date of the last follow-up visit for patients who are still alive or lost to follow-up.
Change From Baseline to Cycle 3 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale Baseline and Cycle 3 Lung Cancer Symptom Scale (LCSS) consist of 9 items that assess the symptoms of lung cancer during the past days on a 10-points scale with 0 as no symptoms and 10 as worse symptoms. The individual item score was translated onto a 0-100 point scale with lower values indicating worse symptoms. An average of the aggregate score of all 9 items was used for a total score. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at 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 Lung Cancer Symptom Scale (LCSS) consist of 9 items that assess the symptoms of lung cancer during the past days on a 10-points scale with 0 as no symptoms and 10 as worse symptoms. The individual item score was translated onto a 0-100 point scale with lower values indicating worse symptoms. An average of the aggregate score of all 9 items was used for a total score. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Change From Baseline to Cycle 3 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA) Baseline and Cycle 3 The overall quality of life (QOL) question was on a 10-points scale with 0=as bad as it can be and 10=as good as it can be. The QOL scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Change From Baseline to Cycle 5 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA) Baseline and Cycle 5 The overall quality of life (QOL) question was on a 10-points scale with 0=as bad as it can be and 10=as good as it can be. The QOL scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Change From Baseline to Cycle 3 in Fatigue Assessed by Treatment-specific Adverse Events Scale Baseline and Cycle 3 The single-item fatigue question was on a 10-points scale with 0=no fatigue and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Change From Baseline to Cycle 5 in Fatigue Assessed by Treatment-specific Adverse Events Scale Baseline and Cycle 5 The single-item fatigue question was on a 10-points scale with 0=no fatigue and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Change From Baseline to Cycle 3 in Neuropathy Assessed by Treatment-specific Adverse Events Scale Baseline and Cycle 3 The single-item neuropathy question was on a 10-points scale with 0=no numbness or tingling in fingers and toes and 10=worst numbness or tingling in fingers and toes imaginable. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Change From Baseline to Cycle 5 in Neuropathy Assessed by Treatment-specific Adverse Events Scale Baseline and Cycle 5 The single-item neuropathy question was on a 10-points scale with 0=no numbness or tingling in fingers and toes and 10=worst numbness or tingling in fingers and toes imaginable. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Change From Baseline to Cycle 3 in Nausea Assessed by Treatment-specific Adverse Events Scale Baseline and Cycle 3 The single-item nausea question was on a 10-points scale with 0=no nausea and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3.
Change From Baseline to Cycle 5 in Nausea Assessed by Treatment-specific Adverse Events Scale Baseline and Cycle 5 The single-item nausea question was on a 10-points scale with 0=no nausea and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5.
Trial Locations
- Locations (215)
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Aurora Presbyterian Hospital
🇺🇸Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸Colorado Springs, Colorado, United States
St. Anthony Central Hospital
🇺🇸Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
St. Joseph Hospital
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
CCOP - Colorado Cancer Research Program
🇺🇸Denver, Colorado, United States
Scroll for more (205 remaining)Mayo Clinic Scottsdale🇺🇸Scottsdale, Arizona, United States