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

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

Sarcoma

Active, not recruiting

2

Start Date 03/01/2016

Age of Trial (yrs) 8.1

Gleevec-resistant

KIT/PDGFRa inhibitor + PD-1 inhibitor

Block KIT + Stimulate the immune system

Specifically GIST plus other cancers

20150932

University of Miami

Breelyn Wilky, MD 305-243-1287 b.wilky@med.miami.edu

Oral

Detailed Description:

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.