Neoplasms

All Conditions

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

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

IV infusion on day 1 of each 3 week cycle, at dose of 200 mg

IV injection on day 1 of each 3 week cycle, starting at dose of 60 mg/m2 (may be escalated to 75 mg/m2 per investigator discretion after Cycle 1)

Megan Jagosky, MD

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.

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.

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

A Pilot Study Evaluating the Safety, Tolerability, and Efficacy of Doxorubicin and Pembrolizumab in Patients With Metastatic or Unresectable Soft Tissue Sarcoma

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.

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.

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.

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.

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.

Merck Sharp & Dohme LLC

Wake Forest University Health Sciences

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

Pembrolizumab: IV infusion on day 1 of each 3 week cycle, at dose of 200 mg

Doxorubicin: IV injection on day 1 of each 3 week cycle, starting at dose of 60 mg/m2 (may be escalated to 75 mg/m2 per investigator discretion after Cycle 1)

Pembrolizumab + Doxorubicin

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Primary Tumor Site

Histology

Metastatic Site

Prior Lines of Systemic Treatment for Sarcoma

Chair of Biostatistics Department

The reported severe or life-threatening adverse event rate with weekly doxorubicin and dacarbazine was 0.55. If it became evident that the rate of severe or life-threatening toxicity convincingly exceeded 0.55, the study would have been halted. Convincing evidence of exceeding 0.55 was based on Bayesian methods and continuous monitoring, where the stopping rule would have held enrollment if the posterior probability at any point exceeded 0.75 or higher.

The evaluable population will consist of all subjects who begin study therapy.

Number of Participants With at Least One Severe or Life-Threatening Adverse Event

The evaluable population consisted of all enrolled subjects who began study therapy.

Overall Survival (OS)

Progression-free Survival (PFS)

The evaluable population will consist of all subjects who begin study therapy and have measurable disease at baseline.

Number of Subjects With an Objective Response

The evaluable population consisted of all enrolled subjects who begin study therapy and achieve objective response (CR or PR) on study treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety, Tolerability, and Efficacy of Doxorubicin and Pembrolizumab for Sarcoma	NCT03056001	Soft Tissue Sar... Soft Tissue Sar...	Pembrolizumab Doxorubicin	12 Years -	Wake Forest University Health Sciences
Safety, Tolerability, and Efficacy of Doxorubicin and Pembrolizumab for Sarcoma	NCT03056001	Soft Tissue Sar... Soft Tissue Sar...	Pembrolizumab Doxorubicin	12 Years -	Wake Forest University Health Sciences
Safety, Tolerability, and Efficacy of Doxorubicin and Pembrolizumab for Sarcoma	NCT03056001	Soft Tissue Sar... Soft Tissue Sar...	Pembrolizumab Doxorubicin	12 Years -	Wake Forest University Health Sciences

Spots Global Cancer Trial Database for soft tissue sarcoma, child