Trabectedin in Combination With Olaparib in Advanced Unresectable or Metastatic Sarcoma

Study Overview
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Brief Summary
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This phase II trial studies how well trabectedin and olaparib work in treating patients with sarcoma that cannot be removed by surgery or has spread to other places in the body. Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing cells, stopping them from dividing or stopping them from spreading. Olaparib may stop the growth of tumor cells by blocking pathways responsible for repairing damaged cells. Giving trabectedin and olaparib may shrink or stop the tumor from growing.

Official Title
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Phase II Multi-Center Trial of Trabectedin in Combination With Olaparib in Advanced Unresectable or Metastatic Sarcoma

Conditions
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Sarcoma, Sarcoma Metastatic

Intervention / Treatment
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* Drug: Olaparib
* Drug: Trabectedin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Age ≥ 16 years Advanced unresectable or metastatic sarcoma Cohort 1: Leiomyosarcoma (LMS)/Liposarcoma (LPS) Cohort 2: Other sarcoma histologies (excluding gastrointestinal stromal tumors) Received at least 1 prior standard chemotherapy. For cohort 1 patients, this must have included a prior anthracycline. Measurable disease by RECIST 1.1 Adequate hematologic, renal, hepatic function Adequate creatine phosphokinase ECOG performance status ≤ 1 Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) Women of childbearing potential and men must agree to use adequate contraception from signing informed consent to at least 6 months (females) and 5 months (men) after study drug treatment Key Exclusion Criteria Prior therapy with PARP inhibitor, including olaparib Prior therapy with trabectedin Additional active malignancy or treatment for alternative cancer (excluding non-melanoma skin cancer) requiring treatment within the past two years Pregnant or breastfeeding women Known hypersensitivity to trabectedin or olaparib Other exclusions per protocol

Ages Eligible for Study
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Minimum Age: 16 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olaparib + Trabectedin<br>There are 2 cohorts. Both cohorts receive the same treatment: Cohort 1: Leiomyosarcoma and liposarcoma Cohort 2: Other bone or soft tissue sarcoma histologies Treatment consists of 21-day cycles for a maximum of 18 months. | Drug: Olaparib<br>* Olaparib taken by mouth twice daily<br>Drug: Trabectedin<br>* Trabectedin administered intravenously (IV) every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Percentage of participants with complete or partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, within each cohort. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Defined as the duration of time from start of treatment to time of progression. Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. Median and 6-month PFS will be estimated along with their 95% confidence intervals. | At 6 months | 
| Progression free survival | Defined as the duration of time from start of treatment to time of progression. Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. Median and 6-month PFS will be estimated along with their 95% confidence intervals. | At approximately 2 years after enrollment | 
| Overall survival | Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. Median, 1- and 2-year OS will be estimated along with their 95% confidence intervals. | At approximately 2 years after enrollment | 
| Incidence of adverse events | The frequency and rates of adverse events occurring in at least 5% of participants and rates of grade 3-5 adverse events will be tabulated by system organ class and preferred term using Common Terminology Criteria of Adverse Events (CTCAE), within each cohort. | Up to 30 days after end of treatment |