Trabectedin in Combination With Olaparib in Advanced Unresectable or Metastatic Sarcoma

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

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Sarcoma Metastatic
• Intervention / Treatment: Drug: Olaparib; Drug: Trabectedin

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olaparib + Trabectedin; 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; Olaparib taken by mouth twice daily; Drug: Trabectedin; Trabectedin administered intravenously (IV) every 21 days

What is the study measuring?

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. reported as survival probability estimates	At 1 year after enrollment
Overall Survival	Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. Median, 1- and 2-year OS probability estimates will be estimated along with their 95% confidence intervals.	At 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, and average of 4.5 months

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: AstraZeneca; Janssen Scientific Affairs, LLC
• Investigators: Principal Investigator: Rashmi Chugh, M.D., University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2020
• Primary Completion (Actual): January 30, 2023
• Study Completion (Actual): September 26, 2024

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dioxoles; Tetrahydroisoquinolines; Isoquinolines; Trabectedin; olaparib
• Other Study ID Numbers: UMCC 2018.132; HUM00161251 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No