Clinical Trial: Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Trial of Concurrent Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma (ASPS) and Other Soft Tissue Sarcomas (STS)

Brief Summary: The investigators hypothesize that combination axitinib with pembrolizumab will improve progression-free survival relative to historical controls.

Detailed Summary:

The study will be a single-institution, open-label, single-arm phase II study. Since the primary endpoint is survival outcome, progression-free survival (PFS) sample size calculation is based on a single-arm survival design. The investigators will employ early stopping rules for lack of efficacy, based on previously reported historical controls (19% PFS at 3 months) and a large database suggesting that a progression-free rate at 3 months of > 40% correlates with an active drug in the second-line setting for patients with advanced sarcoma.

Patients will be treated with twice daily dosing of axitinib alone for the first 7 days, followed by concurrent axitinib administered twice daily at 5 mg orally (PO), plus intravenous administration of pembrolizumab every 21 days. Patients will be assessed every three weeks for toxicity. After the first five patients are enrolled, the investigators will assess safety of the combination. If 2 or fewer patients exhibit dose-limiting toxicity (DLT), the investigators will then proceed with intrapatient titration of axitinib dosing at each cycle based on the presence or absence of predefined toxicities.

Correlative studies characterizing T-cells in tumor tissue and in peripheral blood will be performed at three timepoints: 1. pre-treatment, 2. on-treatment on cycle 3 day 1, and 3. off-study. Additional exploratory imaging investigations, and assessment of circulating tumor cells are included for all patients.

Trial therapy will last until withdrawal of consent, disease progression and/or unacceptable toxicity, whichever occurs first.


Sponsor: Breelyn Wilky

Current Primary Outcome: Rate of Participants Achieving 3-Month Progression-Free Survival (PFS) [ Time Frame: 3 Months after start of protocol therapy ]

Rate of participants who are progression-free at 3 months after the start of protocol therapy, using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Progression-free survival (PFS) is defined as the time from treatment initiation until documented disease progression or death (by any cause, in the absence of progression).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Rate of Participants Achieving Objective Response (ORR) [ Time Frame: 3, 6, and 12 Months after start of protocol therapy ]
    Rate of participants achieving complete response (CR) or partial response (PR) at 3, 6 and 12 months after the start of protocol therapy, according to RECIST version 1.1 criteria.
  • Rate of Participants Achieving Clinical Benefit (CBR) [ Time Frame: 3, 6, and 12 Months after the start of protocol therapy ]
    Rate of participants achieving complete response (CR), partial response (PR) or stable disease (SD) at 3, 6 and 12 months after the start of protocol therapy, according to RECIST version 1.1 criteria.
  • Overall Survival (OS) [ Time Frame: Through Study Completion, an Average of 12 months ]
    The elapsed time from participant enrollment to death or date of censoring.
  • Rate of Participants Experiencing Adverse Events [ Time Frame: Up to 30 days after the end of protocol therapy ]
    Rate of participants experiencing adverse events up to 30 days after the end of protocol therapy.


Original Secondary Outcome: Same as current

Information By: University of Miami

Dates:
Date Received: December 14, 2015
Date Started: April 19, 2016
Date Completion: March 2019
Last Updated: March 9, 2017
Last Verified: March 2017