This phase I/II trial studies the side effects and best dose of doxorubicin hydrochloride when given together with pembrolizumab and to see how well they work in treating patients with sarcoma that have spread to other parts of the body or that cannot be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride, 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. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving doxorubicin hydrochloride together with pembrolizumab may work better in treating patients with sarcoma.
PRIMARY OBJECTIVES: I. To assess the safety and tolerability of the combination of pembrolizumab and doxorubicin hydrochloride (doxorubicin) in patients with advanced soft tissue sarcoma (STS). II. To assess the clinical response rate of advanced soft tissue sarcoma (STS) patients receiving the combination of pembrolizumab and doxorubicin. SECONDARY OBJECTIVES: I. To explore the clinical activity of pembrolizumab in subjects with advanced STS with respect to time to response. II. To explore the clinical activity of pembrolizumab in subjects with advanced STS with respect to duration of response. III. To explore the clinical activity of pembrolizumab in subjects with advanced STS with respect to progression-free survival (PFS). IV. To explore the clinical activity of pembrolizumab in subjects with advanced STS with respect to overall survival. TERTIARY OBJECTIVES: I. To compare response rates between patients with high levels of PD-L1 expression with those who have PD-L1 absent. OUTLINE: This is a phase I, dose-escalation study of doxorubicin hydrochloride followed by a phase II study. Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and doxorubicin hydrochloride IV over 1-3 hours on day 1 of courses 2-7 only. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Maximum Tolerated Dose (MTD) of Doxorubicin Hydrochloride Plus Pembrolizumab According to the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) Version 4.0 (Phase I)
Defined as a dose limiting toxicity (DLT) in less than 2 of 6 subjects. Only Phase 1 subjects will be evaluated for MTD.
Time frame: Up to 42 days (6 weeks)
Objective Response Rate (ORR) (Phase II)
Evaluated per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT. Complete Response (CR) is a complete elimination of the tumor; Partial Response (PR) is 30% reduction. If a subject experienced a PR, this was required to be confirmed with a second scan at the next appropriate cycle.
Time frame: Up to 2 years
Duration of Response
Duration of response is the mean time to progression for all subjects who responded.
Time frame: Up to 2 years
Median Progression-free Survival (PFS)
The Kaplan-Meier method will be used to estimate median PFS.
Time frame: Up to 2 years
Overall Survival (OS)
The Kaplan-Meier method will be used to estimate median OS.
Time frame: Up to 2 years
Time to Response
Average time to response
Time frame: Up to 2 years
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