Advanced or Metastatic Liposarcoma or Leiomyosarcoma Clinical Trial
Official title:
Multicenter, Open-label Study of YONDELIS (Trabectedin) in Subjects With Locally Advanced or Metastatic Liposarcoma or Leiomyosarcoma
The purpose of this study is to find the optimal dose of trabectedin for Chinese patients with locally advanced or metastatic L-sarcoma (liposarcoma or leiomyosarcoma) who were previously treated (in any order) with at least an anthracycline and ifosfamide containing regimen, or an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen (Part 1) and to evaluate whether the overall survival (OS) of the trabectedin group is superior to dacarbazine group (Part 2).
The study is divided into 2 separate parts (ie, Part 1 and Part 2). Part 1 is a dose finding part (to find the optimal dose) of trabectedin for Chinese patients, and Part 2 is a multicenter, randomized (the study medication is assigned by chance), active-controlled (an active substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), parallel-group (a study comparing the response in two or more groups of patients receiving different interventions), open-label (all people know the identity of the intervention) bridging part comparing the efficacy and safety of the optimal dose of trabectedin with dacarbazine in the same population as in Part 1. The study (in both Part 1 and Part 2) will consist of a screening phase, a treatment phase and a follow-up phase. Part 1: Optimal dose (ie, maximum tolerated dose [MTD]) is determined from the following 3 dose levels: Dose level 1 (1.5 mg/m2), Dose level 2 (1.2 mg/m2), and Dose level 3 (1.0 mg/m2)of trabectedin. Cohorts of 6 patients will be treated at each dose level. To determine MTD, dose limiting toxicity (DLT; any pre-defined adverse event that occurs during the first cycle ie, Cycle 1) will be determined. In the first cohort of 6 patients, (a) if DLT is less than or equal to 1 at a dose level, it is considered as MTD (b) if DLT is greater than 2, patients will be de-escalated to next dose level (c) if DLT is equal to 2, 3 more patients will be included at that dose level and if there will be no DLT in those 3 patients, that dose level is considered as MTD. Part 2: If the optimal dose found in Part 1 is 1.5 mg/m2, approximately 48 patients will be randomly assigned to either the trabectedin (approximately 32 patients) or dacarbazine (approximately 16 patients) treatment group in Part 2. If the optimal dose found in Part 1 is below 1.5 mg/m2, 123 patients will be randomly assigned to either the trabectedin (approximately 82 patients) or dacarbazine (approximately 41 patients) treatment group. Safety will be evaluated by assessing adverse events, clinical laboratory test, multiple gated acquisition scans, electrocardiograms, vital signs, and physical examination throughout the study up to 30 days after the end of treatment. ;