Detailed Description
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.
Eligibility Criteria
Age Range: 18 years to No maximum
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