Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
RATIONALE: 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 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. Bevacizumab may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium may stop the growth of tumor cells by blocking some enzymes needed for cell growth. It is not yet known whether giving bevacizumab or pemetrexed disodium alone or in combination is more effective in treating non-squamous non-small cell lung cancer.
PURPOSE: This randomized phase III trial is studying bevacizumab and pemetrexed disodium alone or in combination after induction therapy to see how well they work in treating patients with advanced non-squamous non-small cell lung cancer.
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Phase III Study of Maintenance Therapy With Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed Following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC|
- Overall survival [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
- Objective response as measured by RECIST [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Association between bevacizumab and pemetrexed disodium population pharmacokinetics [ Designated as safety issue: No ]
- Association between proteomic profiles and ICAM, VEGF, and FGF-beta with the clinical outcomes (Closed as of 04/01/2010) [ Designated as safety issue: No ]
|Study Start Date:||August 2010|
|Estimated Primary Completion Date:||April 2018 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive bevacizumab IV over 30-90 minutes on day 1
Experimental: Arm II
Patients receive pemetrexed IV over 10 minutes on days 1.
Drug: pemetrexed disodium
Experimental: Arm III
Patients receive bevacizumab as in arm I and pemetrexed as in arm II.
Given IVDrug: pemetrexed disodium
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- To compare the overall survival (OS) of patients with advanced non-squamous non-small cell lung cancer (NSCLC) treated with maintenance therapy with bevacizumab vs pemetrexed disodium vs bevacizumab and pemetrexed disodium following induction therapy.
- To determine the response rate in patients treated with these regimens.
- To evaluate the progression-free survival (PFS) of patients treated with these regimens.
- To define the toxicity of these regimens in these patients.
- To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA, and ERCC-118 TT in patients treated with induction therapy comprising paclitaxel, carboplatin and bevacizumab and determine the association between genotypes and response rate.
- To determine the association between bevacizumab and pemetrexed disodium population pharmacokinetics and patient-specific covariate with bevacizumab or pemetrexed disodium toxicity.
- To determine the frequency of TSER*3 polymorphisms in NSCLC and the association between TSER polymorphisms and benefit from pemetrexed disodium.
- To evaluate TS and ERCC1 expression by RT-PCR and MTAP mutations in existing tumor specimens as a predictor of pemetrexed disodium response.
- To evaluate polymorphisms within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 collectively or monogenically as markers for variation in efficacious and/or toxic response of individuals to treatment with taxanes.
- To explore the association between proteomic profiles and ICAM, VEGF, and FGF-beta with the clinical outcomes of the study (OS, PFS, and response) (Closed as of 04/01/2010).
- To evaluate the ability of FOX03a to predict first-line treatment outcome in non-squamous NSCLC.(Closed as of 04/01/2010)
- To evaluate the ability of ADSS1 to predict outcome of pemetrexed maintenance treatment in non-squamous NSCLC.(Closed as of 04/01/2010)
- To develop proteomic classifiers to identify patient populations that would benefit from bevacizumab or pemetrexed therapy.(Closed as of 04/01/2010)
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to gender (male vs female), stage of disease (IIIB-T4Nx [with nodule in ipsilateral lung lobe and not candidate for combined chemotherapy and radiation] and IV M1a vs IV M1b vs recurrent), best response to first-time therapy (complete response/partial response vs stable disease), and smoking status (never vs smoker).
- Induction therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Treatment begins within 6 weeks of the last day of induction chemotherapy administration.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1.
- Arm II: Patients receive pemetrexed disodium IV over 10 minutes on day 1.
- Arm III: Patients receive bevacizumab as in arm I and pemetrexed as in arm II. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetics, protein biomarkers, proteomic profiling (closed as of 04/01/10), and other analyses.
After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 2-5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01107626
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|Principal Investigator:||Suresh Ramalingam, MD||Emory University|