Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
Basic Trial Information
|Phase III||Biomarker/Laboratory analysis, Treatment||Active||18 and over||NCI, Other||CDR0000666482|
ECOG-E5508, E5508, NCT01107626
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.
Further Study Information
- 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.
- Cytologically or histologically confirmed non-small cell lung cancer (NSCLC)
- Predominant non-squamous histology
- NSCLC not otherwise specified allowed
- Mixed tumors are categorized by the predominant cell type
- Must meet 1 of the following criteria:
- Stage IV disease including M1a or M1b stages or recurrent disease
- Stage IIIB (T4NX) disease with ipsilateral lung lobe allowed provided patients are not candidates for combined chemotherapy or radiotherapy
- Measurable or non-measurable disease as defined by RECIST criteria
- Patient must have an overall stable or better response after 4 courses of induction therapy
- No cavitary lesions in the lungs
- Patients with brain metastasis must have received local therapy to the brain and have no evidence of progression in the brain for at least 2 weeks from the time of completion of local therapy, prior to registration
- ECOG performance status 0-1
- Leukocytes ≥ 3,000/mm^3
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Total bilirubin ≤ institutional upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN
- Creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min
- Urine protein:urine dipstick ≤ 0-1+ (if > 1+, urine protein creatinine ratio must be < 1)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must agree to abstain from sexual intercourse or to use adequate contraceptive methods during and for at least 6 months after completion of study therapy
- No prior malignancy within the past 3 years except superficial melanoma, basal cell carcinoma, or carcinoma in situ
- No major hemoptysis within the past 4 weeks
- No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Serious cardiac arrhythmia
- Psychiatric illness and/or social situations that would limit compliance with study requirements
- Patients with hypertension must be adequately controlled (BP < 150/100 mm Hg) with appropriate anti-hypertensive therapy or diet
- No history of arterial thrombotic events or major bleeding within the past 12 months
- No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months
- No significant traumatic injury in the past 3 months
- No clinically significant cardiovascular disease
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No history of serious non-healing wounds, ulcers, or bone fractures
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 12 months since prior adjuvant chemotherapy
- At least 2 weeks since prior radiotherapy
- Patients must not have had any major surgery such as thoracotomy, laparotomy, craniotomy, or significant traumatic injury within 6 weeks prior to registration
- Biopsy procedures and chest tube insertion are not considered major surgery for the purpose of this protocol
- More than 7 days since a core biopsy
- Concurrent therapeutic anti-coagulation allowed
- No prior systemic chemotherapy for advanced stage lung cancer
- No prior paclitaxel, pemetrexed disodium, or bevacizumab
- Prior carboplatin allowed provided it was given as part of adjuvant chemotherapy
- No concurrent anti-retroviral therapy in patients with HIV infection
Trial Contact Information
Trial Lead Organizations/Sponsors
Eastern Cooperative Oncology Group
- National Cancer Institute
CCOP - Colorado Cancer Research Program
Sacred Heart Medical Oncology Group
James F Watkins
Emory University Hospital Midtown
Medical and Surgical Specialists, LLC
Nguyet A Le-Lindqwister
La Grange Memorial Hospital
Renee H. Jacobs
Veterans Affairs Medical Center - Indianapolis
Lawrence H. Einhorn
CCOP - Iowa Oncology Research Association
Robert J Behrens
University of Michigan Comprehensive Cancer Center
CCOP - Montana Cancer Consortium
Benjamin Thomas Marchello
CCOP - Missouri Valley Cancer Consortium
Gamini S. Soori
Carol G. Simon Cancer Center at Morristown Memorial Hospital
Dennis A Lowenthal
Dennis A Lowenthal
Bismarck Cancer Center
John T Reynolds
Cancer Center at Phoenixville Hospital
Carl W. Sharer
Cancer Center of Chester County
William E. Luginbuhl
AnMed Cancer Center
CCOP - Virginia Mason Research Center
Craig R. Nichols
Oncology Alliance, SC - Milwaukee - South
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01107626
ClinicalTrials.gov processed this data on April 09, 2015
Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.