Trabectedin in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors

Any Grade 3 or Grade 4 non-hematologic toxicity attributable to the Investigational drug with the specific exclusion of: Grade 3 nausea and vomiting; Grade 3 transaminase (AST/ALT) elevation that return to less than or equal to Grade 1 or baseline prior to the time for the next treatment cycle; Grade 3 fever or infection; Alopecia; Grade 4 neutropenia of \> 7 days duration or Grade 4 thrombocytopenia of \> 7 days duration, which requires transfusion therapy on greater than 2 occasions in 7 days, or which causes a delay of more than 14 days beyond the planned interval between treatment cycles.

Time frame: 1 Cycle

Population: Two pts in Group 1 and 1 pt in Group 2 were excluded because they were removed from therapy prior to the DLT evaluation period and no DLT had been observed. No patients in Groups 3, 4, or 5 were evaluated for DLT.

The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated Vss was derived for each patient.

Time frame: From baseline up to168 hours after trabectedin infusion in course 1

Population: Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate apparent volume at steady state of trabectedin of trabectedin. Group 1 and group 2 patients were excluded due to not submitting specimens.

The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated AUC was derived for each patient.

Time frame: From baseline up to168 hours after trabectedin infusion in course 1

Population: Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate trabectedin AUC. Group 1 and group 2 patients were excluded due to not submitting specimens.

The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated Clearance was derived for each patient.

Time frame: From baseline up to168 hours after trabectedin infusion in course 1

Population: Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate trabectedin clearance. Group 1 and group 2 patients were excluded due to not submitting specimens.

The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated Half-life was derived for each patient.

Time frame: From baseline up to168 hours after trabectedin infusion in course 1

Population: Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate trabectedin half life. Group 1 and group 2 patients were excluded due to not submitting specimens.

The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated Cmax was derived for each patient.

Time frame: From baseline up to168 hours after trabectedin infusion in course 1

Population: Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate maximum plasma concentration of trabectedin. Group 1 and group 2 patients were excluded due to not submitting specimens.

Any patient who is enrolled and receives at least one dose of trabectedin will be considered evaluable for response if the individual receives at least one dose of trabectedin and: (1) is removed from protocol therapy because of progressive disease where progressive disease is documented either by imaging studies or clinical progression; or (2) has at least one radiographic evaluation of disease status after the start of protocol therapy and is not electively removed from protocol therapy with stable disease or is not lost to follow-up with stable disease. Patients who achieve a complete response (CR) - disappearance of all target lesions or partial response (PR) - \>=30% decrease in the sum of the longest diameter of target lesions according to the RECIST criteria will be considered responders for the study design. All other patients who are evaluable for response will be considered non-responders for the study.

Time frame: Twenty-six (26) cycles of chemotherapy or termination of protocol therapy, whichever occurs first.

Population: No pts in Group 1 were evaluated for response. 1 pt in Group 3 is excluded because the pt was removed from protocol therapy after cycle 3 when a cardiac evaluation was missed. The pt was removed prior to disease assessment on protocol therapy. 1 pt enrolled in Group 4 was excluded because patient was removed from therapy prior to chemotherapy.