Overview

This trial is active, not recruiting.

Condition advanced non-small cell lung cancer
Treatments pemetrexed, carboplatin, paclitaxel, bevacizumab
Phase phase 3
Target VEGF
Sponsor Eli Lilly and Company
Start date September 2009
End date January 2013
Trial size 361 participants
Trial identifier NCT00948675, 13258, H3E-US-S130

Summary

The purpose of this study is to compare the regimens of pemetrexed, carboplatin with pemetrexed maintenance and paclitaxel, carboplatin, bevacizumab with bevacizumab maintenance in participants with Stage 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 and Carboplatin followed by Pemetrexed
pemetrexed ALIMTA, LY231514
Induction therapy: 500 milligrams/square meter (mg/m²) given intravenously every 21 days for 4 cycles. Maintenance therapy: 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.
carboplatin
Induction Therapy (every 21 days for 4 cycles): Area Under the Curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes.
(Active Comparator)
Paclitaxel, Carboplatin, and Bevacizumab followed by Bevacizumab
carboplatin
Induction Therapy (every 21 days for 4 cycles): Area Under the Curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes.
paclitaxel
Induction Therapy (every 21 days for 4 cycles): 200 mg/m² intravenously infused over 3 hours
bevacizumab
Induction therapy: 15 milligrams/kilogram (mg/kg) given intravenously every 21 days for 4 cycles. Maintenance therapy: 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.

Primary Outcomes

Measure
Progression Free Survival Without Grade 4 Toxicity (G4PFS) as Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
time frame: Randomization to measured progressive disease or treatment discontinuation up to 39.49 months

Secondary Outcomes

Measure
Progression Free Survival (PFS)
time frame: Randomization to measured progressive disease up to 39.49 months
Overall Survival (OS)
time frame: Randomization to date of death from any cause up to 39.49 months
Percentage of Participants With Complete Response or Partial Response (Overall Tumor Response Rate)
time frame: Baseline to date of objective progressive disease up to 39.49 months
Disease Control Rates Defined as Complete Response (CR), Partial Response (PR), and Stable Disease (SD)
time frame: Baseline to date of objective progressive disease up to 39.49 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - a histologic or cytologic diagnosis of advanced non-small cell lung cancer (NSCLC) [Stage IV from the American Joint Committee on Cancer Staging Criteria (AJCC) staging system, version 7.0, including both M1a and M1b], other than predominantly squamous cell histology, that is not amenable to curative therapy. Participants may not have received any prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy, including adjuvant therapy, for any stage of NSCLC. - prior radiation therapy is allowed to < 25% of the bone marrow; however, prior radiation to the whole pelvis not allowed. - good performance status. - adequate organ function. - estimated life expectancy of at least 12 weeks. Exclusion Criteria: - known central nervous system (CNS) disease, other than treated brain metastasis. - major surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days prior to study or have an anticipated need for major surgery during the study. - core biopsy or other minor surgical procedure, excluding placement of vascular access device, closed pleurodesis, thoracentesis, and mediastinoscopy, within 7 days prior to study. - history of gastrointestinal fistula, perforation, or abscess, inflammatory bowel disease, or diverticulitis. - currently receiving ongoing treatment with full-dose warfarin or equivalent - significant vascular disease within 6 months prior to Day 1 of Cycle 1. - evidence of bleeding diathesis or coagulopathy. - serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol. - serious cardiac condition, such as myocardial infarction, angina, or heart disease. - inadequately controlled hypertension. - any prior history of hypertensive crisis or hypertensive encephalopathy. - serious, nonhealing wound, active ulcer, or untreated bone fracture. - another active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within the last 5 years. - previously received treatment with paclitaxel, carboplatin, pemetrexed, or bevacizumab (prior intravitreal administration of bevacizumab does not preclude study participation). - pregnant or breast-feeding. - history of stroke or transient ischemic attack within 6 months prior to study. - known sensitivity to any component of paclitaxel, carboplatin, pemetrexed, or bevacizumab. - history of hemoptysis within 3 months prior to randomization. - unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). - unwilling to take folic acid or vitamin B12 supplementation. - clinically significant third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage. Participants with M1a disease with pleural effusions are eligible if the effusions can be adequately controlled.

Additional Information

Official title A Study of Pemetrexed Plus Carboplatin Followed by Maintenance Pemetrexed vs Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Advanced NCSLC of Nonsquamous Histology
Description This is a multicenter, randomized, open-label, Phase III trial. Eligible participants will be randomized in a 1:1 ratio to receive pemetrexed and carboplatin followed by pemetrexed or paclitaxel, carboplatin, and bevacizumab followed by bevacizumab as their study treatment. Participants randomized to Pemetrexed + Carboplatin + Pemetrexed will receive folic acid, vitamin B12, and dexamethasone as stated in the pemetrexed label. Before administration of paclitaxel, participants randomized to Paclitaxel + Carboplatin + Bevacizumab will receive premedication (dexamethasone, diphenhydramine, and cimetidine or ranitidine) as recommended in the paclitaxel label.
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.