Metronomic Trabectedin, Gemcitabine, and Dacarbazine for Leiomyosarcoma

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

Detailed Description
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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 250 mg/m2 i.v. on D1 and D8, and dacarbazine 250 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.

Official Title
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TAGGED: A Phase 2 Study Using Low Dose/Metronomic Trabectedin, Gemcitabine, and Dacarbazine as 2nd/3rd/4th Line Therapy for Advanced Leiomyosarcoma

Conditions
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Leiomyosarcoma

Intervention / Treatment
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* Drug: Trabectedin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open label phase 2 study using metronomic doses of trabectedin, gemcitabine and dacarbazine given intravenously.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Trabectedin 24 h CIV 0.5 mg/m2 D1 and D8 Gemcitabine i.v. 250 mg/m2 D1 and D8 Dacarbazine i.v. 250 mg/m2 D1 and D8 | Drug: Trabectedin<br>* This is an open label phase 2 study using metronomic doses of trabectedin, gemcitabine and dacarbazine given intravenously.<br>* Other names: Dacarbazine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression free survival up to disease progression or death from any cause | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response | Best overall response (BOR) and duration of response (DOR) by RECIST v1.1 via CT scan or MRI | 6 weeks | 
| Adverse Event | Incidence of treatment-related adverse events | 12 months |