Safety, Tolerability, and Efficacy of Doxorubicin and Pembrolizumab for Sarcoma

Phase 2

Completed

Conditions: Soft Tissue Sarcoma, Adult
Soft Tissue Sarcoma, Child

Interventions: Drug: Pembrolizumab
Drug: Doxorubicin

Registration Number: NCT03056001

Lead Sponsor: Wake Forest University Health Sciences

Brief Summary: The purpose of this study is to evaluate the safety, tolerability and efficacy of doxorubicin in combination with pembrolizumab in subjects with metastatic or unresectable soft tissue sarcoma. Based on previous studies, pembrolizumab may be an effective study treatment.

Detailed Description: The primary objective of this study is to assess the safety and toxicity profile of doxorubicin and pembrolizumab in previously treated or untreated subjects with unresectable or metastatic soft tissue sarcoma. The secondary objectives are to assess overall survival, and response rate, duration of response, and progression-free survival (PFS) with this regimen using RECIST 1.1 criteria. The exploratory objectives are to assess PFS, overall response rate, duration of response, and disease control rate using the immune-related RECIST (irRECIST) criteria, evaluate the correlation between PD-L1 expression levels and antitumor activity of MK-3475, investigate other biomarkers that may correlate with tumor responses, and evaluate differences in tumor tissue characteristics in biopsies taken during or post-treatment with MK-3475 versus baseline.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + doxorubicin	Pembrolizumab	Participants will receive pembrolizumab IV infusion and doxorubicin IV injection on Day 1 of every 21 (+/- 3) days
Pembrolizumab + doxorubicin	Doxorubicin	Participants will receive pembrolizumab IV infusion and doxorubicin IV injection on Day 1 of every 21 (+/- 3) days

Primary Outcome Measures

Name	Time	Method
Number of Participants With at Least One Severe or Life-Threatening Adverse Event	From enrollment to at least 90 days following cessation of study treatment. The median time on treatment was 5.8 months.	Severe or life-threatening adverse events will be determined for each subject as a binary variable indicating whether or not the subject experienced at least one adverse event that meets the following criteria: is considered a serious adverse event (per CFR 21 Part 312), is study treatment related per the Sponsor-Investigator, and considered to be clinically significant by the Sponsor-Investigator. An adverse event will be considered study treatment related if it is determined that the event is at least possibly related to either pembrolizumab, doxorubicin, or both.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DoR)	From date of response to date of progression/death, or censored as described above; assessed for approximately 2 years.	Duration of Response (DoR) is defined as the duration of time from the first assessment that determined a CR or PR to the date of the first occurrence of progressive disease or death. Progression events and the censoring mechanism for DoR will be the same as described for PFS. DoR will be determined for each subject using the RECIST 1.1 criteria.
Overall Survival (OS)	From treatment start to date of death, or censored as described; assessed for approximately 5 yrs or until censoring rate for entire study reduced to 20%, whichever occurred first. When the censoring rate reached 20%, OS time ranged from 0.1 - 4.8 yrs.	OS is defined as the duration from treatment start date to the date of death from any cause. Subjects who are alive or lost to follow up at the time of the analysis will be censored at the last known date they were alive.
Progression-free Survival (PFS)	From treatment start date to date of progression/death, or censored as described; assessed for approximately 2 years.	PFS is defined as time from enrollment to time of progression or death. Disease progression (PD) may be determined objectively per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, where PD is defined as a 20% increase in the sum of longest diameters of target lesions, a measurable increase in non-target lesion, or appearance of new lesions) or subjectively as determined by investigator (with evidence documented in the medical records). If the subject died without documented PD, date of progression will be date of death. For surviving subjects who did not have documented PD, PFS was censored at last radiologic assessment. For subjects who received subsequent anticancer therapy prior to documented PD, PFS was censored at last radiologic assessment prior to commencement of subsequent therapy. Subjects who experienced a PFS event following an interval equal to two or more scheduled radiologic assessments were censored at last assessment prior to first missed assessment.
Number of Subjects With an Objective Response	From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for a median of 5.8 months)	Objective response was determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of complete response (CR) or partial response (PR) as determined by RECIST 1.1 response criteria. A CR is indicated by disappearance of all target and non target lesions. A PR is indicated by \>=30% decrease in sum of longest diameter of target lesions with baseline as reference.