Trabectedin for Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma

The objective of this study is to facilitate access to trabectedin for eligible previously treated subjects with soft tissue sarcoma (STS), who cannot be expected to benefit from currently available therapeutic options for treatment of STS but who may benefit from treatment with trabectedin.

This study is designed to accommodate individual requests for treatment with trabectedin before the drug becomes commercially available. In regions where trabectedin becomes commercially available and reimbursable in that particular country, an administrative cutoff for further accrual will be set.

Subjects with STS who have relapsed following standard of care treatment or who are refractory to or intolerant of standard therapies but who may benefit from treatment may participate in this study. The safety profile of the drug will be further evaluated.

Eligible subjects will receive a dose of 1.5 mg/m2 trabectedin intravenous (i.v.) formulation administered as a 24-hour infusion on Day 1 of each 17- to 49-day treatment cycle.

Tumor assessment will be performed prior to administration of the first dose (Cycle 1, Day 1) and thereafter approximately every 2 cycles according to institutional standards.

The number of cycles is not specified for this study. Subjects may continue to receive treatment as long as they derive an overall clinical benefit, i.e., until there is clear evidence of disease progression or unacceptable toxicity, as judged by the investigator.

Safety evaluation will include physical examinations, monitoring vital signs and adverse events, and collecting hematology and clinical chemistry test results. Minimal efficacy data will be collected and includes tumor assessments and survival information.

An administrative cutoff for further study accrual will be set in regions where trabectedin commercially becomes available and reimbursable in that particular country if applicable.

Inclusion Criteria:

• Male or female subject aged ≥18 years.
• Unresectable advanced or metastatic histologically proven STS. Eligibility will include desmoplastic small round cell tumor, Ewing's sarcoma, and osteosarcoma.
• Subjects must have relapsed or had progressive disease following standard of care treatment with chemotherapy prior to enrollment or intolerant to prior standard of care treatment with chemotherapy due to safety issues.
• Recovery from toxic effects of prior therapies to Grade 1 or better according to National Cancer Institute-Common Terminology Criteria of Adverse Events (NCI-CTCAE, Version 3).
• Hematologic test results:
• Hemoglobin ≥8 g/dL
• Absolute neutrophil count (ANC) ≥1,500/μL
• Platelet count ≥100,000/μL
• Clinical chemistry test results:
• If serum creatinine ≤1.5 times the upper limit of normal (ULN), or if serum creatinine is >1.5 times the ULN, then 24 hour creatinine clearance of >50 cc/min, creatine phosphokinase (CPK) ≤2.5 times the ULN
• Hepatic function test results:
• Total bilirubin ≤ULN, if increased then measure indirectly to rule out Gilbert's syndrome. If direct bilirubin is within normal limits, subject may be considered eligible.
• Total alkaline phosphatase ≤1.5 times the ULN, or if liver metastases are present, then alkaline phosphatase may be ≤2.5 times the ULN.
• AST and ALT must be ≤2.5 times the ULN.
• Female subjects must be surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch) before entry and throughout the study, and have a negative urine or serum pregnancy test result at screening. For male subjects and partners, acceptable methods of birth control include sterilization, barrier contraception, and abstinence.
• Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

• Less than 3 weeks from the last dose of radiation therapy; last dose or 4 half lives of systemic cytotoxic therapy; therapy with any investigational agent; less than 2 weeks from the last dose of radiation therapy with any investigational agent or systemic therapy, provided all side effects from those therapies have resolved to Grade 1 or less.
• Active viral hepatitis or chronic liver disease.
• Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within 1 year before enrollment, uncontrolled arterial hypertension or arrhythmias.
• Active infection.
• Female subject who is pregnant or breast-feeding.