Metronomic Trabectedin, Gemcitabine, and Dacarbazine for Soft Tissue Sarcoma

This is an open label phase 2 study using metronomic doses of trabectedin, gemcitabine and dacarbazine given intravenously.

A total of 80 patients will receive trabectedin 0.5 mg/m2 as 24 hour continuous intravenous infusion (CIV) on D1 and D8, gemcitabine 200 mg/m2 i.v. on D1 and D8, and dacarbazine 200 mg/m2 i.v. on D1 and D8 (see product information; www.accessdata.fda.gov). Treatment cycles are given every 3 weeks. Patients in this study may continue treatment until significant disease progression or unacceptable toxicity occurs up to one year of therapy. Patients who withdraw or do not complete the first 2 treatment cycles and first follow up CT scan/MRI will be replaced.

Inclusion criteria

• Male or Female ≥ 18 years of age
• Pathologically confirmed diagnosis of locally advanced, unresectable or metastatic leiomyosarcoma
• Previously treated patient with measurable disease by RECIST v1.1
• ECOG performance status ≤ 2
• Life expectancy of at least 3 months
• Acceptable liver function: Bilirubin < 1.5 times upper limit of normal (ULN; except subjects with Gilbert Syndrome who must have a total bilirubin level < 3.0 ULN); AST (SGOT), ALT (SGPT) and alk phos < 2.5 x ULN (< 5 x ULN if liver metastases present)
• Acceptable renal function: Creatinine < 1.5 times ULN and creatinine clearance > 60 ml/min using the Crockroft-Gault formula
• Acceptable hematologic status: ANC >1000 cells/μL; Platelet count >100,000/μL; Hemoglobin > 9.0 g/dL
• INR and PT < 1.5 ULN unless taking anti-coagulation, in which case PT, INR and aPTT must be within therapeutic range of intended use of anticoagulants
• Ability to understand the purposes and risks of the study and has signed and dated a written informed consent form approved by the Investigator's IRB/Ethics Committee
• Willingness to comply with all study procedures and availability for the duration of the study
• All women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours of enrollment. If urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; all subjects must agree to use highly effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 5 months for women and 7 months for men after the last dose.

Exclusion criteria

• Currently receiving treatment with another investigational device or drug study, or <14 days since ending treatment with another investigational device or drug study(s).
• Subject has known sensitivity to trabectedin, gemcitabine or dacarbazine.
• Female subject is pregnant or breast-feeding or planning to become pregnant during study treatment and through 3 months after the last dose of trabectedin, gemcitabine or dacarbazine.
• Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of trabectedin, gemcitabine or dacarbazine.
• Sexually active subjects and their partners unwilling to use male or female latex condom