metronomic trabectedin, gemcitabine, and dacarbazine for soft tissue sarcoma

Conditions: Leiomyosarcoma

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

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:
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 \ 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