A Phase II Study to evaluate activity and toxicity of Gemcitabine in Combination with Pemetrexed long term infusion in the Treatment of pretreated Metastatic Colorectal Cancer Patients~Study Design:~Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination.~Study Duration~Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks).~Total duration of the study: 24 months.~Primary objective:~- objective response rate (ORR: CR+PR+SD)~Secondary objectives:~safety profile of the drugs combination;~time to progression (TTP) and overall survival (OS)~Number of Subjects:~Approximately 38 subjects will be enrolled on study:~- First stage:12 patients enrolled~If 1 or 0 responses were observed, the trial had to be terminated:~- Second stage: an additional of 23 patients were to be enrolled. If 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.~Statistical Methodology:~A minimax two-stage Simon design will be employed. A 10% response will preclude further study, whereas a 30% response rate will indicate that further study would be warranted. Using α and β errors of 0.10 and 0.10, respectively, 12 patients will be enrolled in the first stage, and if 1 or 0 responses were observed, the trial had to be terminated. Otherwise, an additional of 23 patients were to be enrolled, and if 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.~The first 6 enrolled patients will be closely controlled for safety and further patients will be enrolled only in absence of severe toxicity resulting in discontinuation 1 month after the first cycle of the six patients.~The primary analysis will be performed on the ITT (Intention To Treat) population. PFS and OS will be estimated by the Kaplan-Meier method. The HR for PFS and OS will be estimated according to the Cox model, with its relative 95% confidence.~A secondary analysis will be performed on the PP (per-protocol) population. The Overall Response Rate to study treatment will be reported on the ITT and PP population with 95% confidence interval. Results will be tabulated and not evaluable patients will be included as additional category.
Study Design:~Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination.~Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks).~Total duration of the study: 24 months.~Number of Subjects:~Approximately 38 subjects will be enrolled on study:~- First stage:12 patients enrolled~If 1 or 0 responses were observed, the trial had to be terminated:~- Second stage: an additional of 23 patients were to be enrolled. If 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.