This phase I/II studies the side effects of avelumab and trabectedin and how well they work in treating patients with leiomyosarcoma or liposarcoma that has spread to other places in the body (metastatic) or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving avelumab and trabectedin may work better in treating patients with liposarcoma or leiomyosarcoma.
PRIMARY OBJECTIVES: I. To assess the safety and tolerability of the combination of trabectedin and avelumab in subjects with advanced leiomyosarcoma and liposarcoma. II. To assess the objective response rate of advanced L-type sarcoma patients receiving the combination regimen of avelumab and trabectedin. SECONDARY OBJECTIVE: I. To further explore the clinical activity and safety profile of avelumab and trabectedin as a combination therapy. OUTLINE: Avelumab will be administered every 2 weeks. Trabectedin will be administered every 3 weeks for the first two doses (Week 1 and Week 4), and then every four weeks (Week 7, Week 11,…) moving forward. After Cycle 2 of trabectedin, dosing may extend to every 5 weeks at investigator discretion, for management of trabectedin-associated toxicity only. Delays of trabectedin beyond 5 weeks may be allowed but require written approval from the Sponsor-Investigator. On days where both drugs are scheduled to be administered, avelumab will be administered first. This will continue until unacceptable toxicity or confirmed disease progression. After completion of study treatment, patients are followed up at 30 and 90 days, then every 12 weeks for 2 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Given IV
Given IV
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Incidence of Adverse Events
Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Time frame: up to 2 years 7 months total
Overall Response Rate (ORR)
Rate of Partial Response (PR) + Complete Response (CR), which is the best response for each subject determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for target lesions and assessed by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan. Partial response is defined as a decrease in 30% or more in the sum of the longest diameter of target lesions, and complete response is defined as disappearance of all evaluable disease. No subjects had a complete response on this study so the ORR represents subjects who had a partial response only.
Time frame: Up to 2 years 7 months total
Time to Response
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Time to response is defined as the amount of time from when the subject first received study treatment (Cycle 1, Day 1) to when they achieved a partial response on trial. With such small numbers, this data is not necessarily representative of what a larger study would report.
Time frame: Up to 2 years 7 months total
Duration of Response
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Duration of response is defined as the amount of time a subject responded to study treatment with either a partial response or complete response until the date of last follow-up (if response ongoing at data cutoff) or the date until they progressed on study.
Time frame: Up to 2 years 7 months total
Progression-free Survival (PFS)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, appearance of new lesions while on study, or clear growth of a non-target lesion.
Time frame: At 12 weeks
Complete Response Rate (CR)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response is defined as disappearance of all evaluable disease.
Time frame: At 12 weeks
Partial Response Rate (PR)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Partial response is defined as a decrease in 30% or more in the sum of the longest diameter of target lesions.
Time frame: At 12 weeks
Stable Disease (SD)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Stable Disease is defined as neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (PD).
Time frame: At 12 weeks
Clinical Benefit Rate
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Clinical Benefit Rate is defined as the percentage of subjects who achieved a Complete Response (CR) + Partial Response (PR) + Stable Disease (SD).
Time frame: At 12 weeks
Median Overall Survival (OS)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: Up to 2 years post End of Treatment, for a total of 3 years
Adverse Event Profile - All Treatment-Related Grade 3-5 Adverse Events
Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: Up to 2 years 7 months total
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