Sponsor and responsibilities

This is an Investigator Initiated Trial in which every Investigator is responsible for the trial procedures in his/her site, according to the protocol and clinical research legislation (local and international). It is not a sponsored trial.

Trial treatment supply

As per the Investigators requirements, Eli Lilly do Brasil will supply Pemetrexed, Carboplatin, Vitamin B12, Folic Acid and Dexamethasone (pre-medication) for Brazilian sites and Eli Lilly USA will supply Pemetrexed for the US site.

Objectives and endpoints

The primary objective is to determine and compare the overall survival produced by pemetrexed and by the combination of pemetrexed plus carboplatin. Secondary objectives are to assess and compare the safety, objective response rate, and progression-free survival.

Design

Phase III, open-label, randomized trial to be conducted in eight centers in Brazil and one in the United States, with centralized 1:1 randomization.

Patient eligibility

Eligible patients will be aged 18 years or older, and will have histologically or cytologically proven, previously untreated NSCLC in stage IIIB or IV, a PS of 2, and adequate organ function.

Treatment plan

Patients in Arm A will receive pemetrexed, 500mg/m2, with appropriate vitamin supplementation; patients in Arm B will receive the same dose and schedule of pemetrexed as in Arm A, in combination with carboplatin, AUC of 5. Treatment cycles will be repeated every 21 days for a maximum of four cycles.

Expected accrual

Approximately 22 months, and patients will be followed for 1 year after completion of treatment.

Patient evaluation

Response will be graded according to the RECIST criteria; toxicity will be graded according to the CTCAE v3.0

Data management/statistical aspects

Patient data collected will be entered by investigators and stored in a CRF for the study. Data collection will be centralized in the Brazilian National Cancer Institute. Approximately 228 eligible patients are needed to provide 80% power to detect a difference between the 2 treatment arms with a type I error of 0.05, assuming that pemetrexed plus carboplatin will result in a median survival of at least 4.3 months, and pemetrexed alone 2.9 months, allowing for a dropout rate of 10%. An interim analysis will be conducted after 46 deaths have occurred, with an alpha of 0.004 as the predetermined level of statistical significance for trial termination.

Ethical aspects

The study will be conducted in accordance with international and local standards, and will be approved by the Institutional Review Boards (IRB) of participating centers

IRB approval

First patient visit

First patient enter treatment

Last patient enter treatment

October 2008

INCA - Instituto Nacional de Câncer

Principal investigators


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