Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatments pemetrexed, paclitaxel, carboplatin, bevacizumab
Phase phase 3
Target VEGF
Sponsor Eli Lilly and Company
Start date December 2008
End date April 2012
Trial size 939 participants
Trial identifier NCT00762034, 9707, H3E-MC-JMHD

Summary

This study will compare overall survival in patients with Stage IIIB or IV nonsquamous non-small cell lung cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab
pemetrexed Alimta
Induction therapy 500 milligram per meter squared (mg/m^2) intravenously (IV) every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
pemetrexed Alimta
Maintenance therapy 500 mg/m^2 IV every 21 days (with bevacizumab) until progressive disease or treatment discontinuation
carboplatin
Induction therapy area under the concentration curve (AUC) 6 IV every 21 days for up to 4 cycles of 21 days
bevacizumab
Induction therapy 15 milligrams per kilogram (mg/kg) IV every 21 days for up to 4 cycles of 21 days
bevacizumab
Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.
(Active Comparator)
Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab
paclitaxel
Induction therapy 200 mg/m^2 IV every 21 days (with carboplatin and bevacizumab) for up to 4 cycles of 21 days
carboplatin
Induction therapy area under the concentration curve (AUC) 6 IV every 21 days for up to 4 cycles of 21 days
bevacizumab
Induction therapy 15 milligrams per kilogram (mg/kg) IV every 21 days for up to 4 cycles of 21 days
bevacizumab
Maintenance therapy 15 mg/kg IV every 21 days until progressive disease or treatment discontinuation.

Primary Outcomes

Measure
Overall Survival
time frame: Baseline to date of death from any cause (up to 37.06 months)

Secondary Outcomes

Measure
Percentage of Participants With a Complete Response (CR) and Partial Response (PR) (Overall Response Rate)
time frame: Baseline to measured progressive disease (up to 37.06 months)
Percentage of Participants With a Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate)
time frame: Baseline to measured progressive disease (up to 37.06 months)
Progression Free Survival Time
time frame: Baseline to measured progressive disease or date of death from any cause (up to 33.54 months)
Time to Progressive Disease
time frame: Baseline to measured progressive disease (up to 37.06 months)
Safety and Toxicity Profile of Study Treatments
time frame: Baseline to study endpoint (up to 37.06 months)
Duration of Hospitalizations Per Participant
time frame: Baseline to study endpoint (up to 37.06 months)
Number of Participants Who Received a Transfusion
time frame: Baseline to study endpoint (up to 37.06 months)
Number of Participants Receiving Concomitant Medication
time frame: Baseline to study endpoint (up to 37.06 months)
Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - General (FACT-G)
time frame: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)
Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - Lung (FACT-L)
time frame: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)
Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity (FACT/GOG-Ntx)
time frame: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Pemetrexed
time frame: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)
Pharmacokinetics (PK): Elimination Half-life (t1/2) for Pemetrexed
time frame: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Pemetrexed
time frame: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)
Pharmacokinetics (PK): Pemetrexed Clearance (CL)
time frame: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Total (Bound and Unbound) Platinum and Unbound Platinum
time frame: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)
Pharmacokinetics (PK): Elimination Half-life (t1/2) for Total (Bound and Unbound) Platinum and Unbound Platinum
time frame: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Total (Bound and Unbound) Platinum and Unbound Platinum
time frame: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)
Pharmacokinetics (PK): Platinum Clearance (CL) for Total (Bound and Unbound) and Unbound Forms
time frame: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Bevacizumab
time frame: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)
Pharmacokinetics (PK): Elimination Half-life (t1/2) for Bevacizumab
time frame: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) Bevacizumab
time frame: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)
Pharmacokinetics (PK): Bevacizumab Clearance (CL)
time frame: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)
Translational Research: Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations
time frame: Baseline
Translational Research: Overall Survival (OS) Based on Nuclear Thyroid Transcription Factor-1 (TTF-1) Expression Regardless of Study Treatment
time frame: Baseline to date of death from any cause (up to 37.06 months)
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Nuclear Thymidylate Synthase (TS) Expression
time frame: Baseline to date of death from any cause (up to 37.06 months)
Translational Research: Overall Survival (OS) Based on Cytoplasmic and Membrane Folate Receptor Alpha (FR-α) Expression
time frame: Baseline to date of death from any cause (up to 37.06 months)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - You must sign an informed consent document for clinical research. - You must have Stage IIIB or Stage IV nonsquamous non-small cell lung cancer. - You must not have received any prior treatment for your disease. - Prior radiation therapy is allowed to < 25% of the bone marrow; however, prior radiation to the whole pelvis is not allowed. If you have had radiation therapy to the chest, you are not eligible to participate. - You must be at least 18 years of age or older. - You must have measureable tumor lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) or disease can be evaluated on computed tomography (CT) scan. - Your test results assessing the function of blood forming tissue, kidneys and liver must be satisfactory. - Women must be sterile, postmenopausal or on contraception and men must be sterile (for example post-vasectomy) or on contraception. Exclusion Criteria: - You cannot have clinically significant third-space fluid collections (e.g. ascites or pleural effusions that cannot be controlled by drainage or other procedures). - You cannot have Non-small Cell Lung Carcinoma (NSCLC) of predominantly squamous cell histology. - You cannot have known central nervous system (CNS) disease, other than stable, treated brain metastasis. - You cannot have undergone a surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days of starting the study treatment, or have an anticipated need for major surgery during the study. - You cannot have a history of gastrointestinal fistula, perforation, or abscess, inflammatory bowel disease, or diverticulitis. - You are currently receiving ongoing treatment with full-dose warfarin or equivalent. - You cannot have significant vascular disease, serious cardiac conditions (such as heart attack), stroke or transient ischemic attack within 6 months of the trial. - You cannot have evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation). - You cannot have inadequately controlled hypertension, or a history of hypertensive crisis or hypertensive encephalopathy. - You cannot have a serious, nonhealing wound, active ulcer, or untreated bone fracture. - You cannot have another form of cancer, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within the last 5 years. - You cannot have received an investigational treatment within 30 days prior to the trial. - You cannot have previously received treatment with paclitaxel, carboplatin, pemetrexed, or bevacizumab. - You cannot be pregnant or breast-feeding. - You cannot have a known sensitivity to any component of paclitaxel, carboplatin, pemetrexed, or bevacizumab. - You cannot have a history of hemoptysis (coughing blood) within 3 months prior to the trial. - You are unable to stop taking aspirin more than 1.3 grams per day or other nonsteroidal anti-inflammatory drugs (NSAIDs). - You are unable or unwilling to take folic acid or vitamin B12 supplementation. - You are unable to take corticosteroids. - You have any other on-going illnesses including active infections that may not allow you to adhere to the requirements of the trial.

Additional Information

Official title Randomized, Open-Label, Phase 3 Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non-Small Cell Lung Cancer
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.