Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas
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|ClinicalTrials.gov Identifier: NCT02636725|
Recruitment Status : Recruiting
First Posted : December 22, 2015
Last Update Posted : March 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Alveolar Soft Part Sarcoma Soft Tissue Sarcomas||Drug: Axitinib Drug: Pembrolizumab Procedure: Blood Draw Procedure: Tumor Specimen Collection||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||April 19, 2016|
|Estimated Primary Completion Date :||March 2019|
|Estimated Study Completion Date :||March 2019|
Experimental: Axitinib + Pembrolizumab
Concurrent Axitinib and Pembrolizumab therapy, with Blood Draw and Tumor Specimen Collection for correlative studies.
Twice daily dosing of axitinib alone for the first 7 days, followed by concurrent axitinib administered twice daily at 5 mg PO twice daily, plus intravenous administration of pembrolizumab every 21 days. Intrapatient dose escalation of axitinib will be performed following an initial safety lead-in of 5 patients.
Other Name: Inlyta
Pembrolizumab 200 mg flat dose shall be administered via intravenous (IV) infusion, once every 21 days, on day 8 and day 29 of the first cycle, and days 1 and 22 of the following cycles.
Procedure: Blood Draw
Peripheral blood draws for correlative studies characterizing T-cells in peripheral blood will be performed at three timepoints: 1) pre-treatment, 2) on-treatment on cycle 3 day 1, and 3) off-study.
Other Name: Phlebotomy
Procedure: Tumor Specimen Collection
Tumor specimen collection via core needle biopsy for correlative studies characterizing T-cells in tumor tissue will occur at three timepoints: 1) pre-treatment, 2) on-treatment on cycle 3 day 1, and 3) off-study.
Other Name: Core-Needle Biopsy
- 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).
- 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.
- Safety and Toxicity Profile: Rate of Toxicity in Study Participants [ Time Frame: Up to 30 days after the end of protocol therapy ]Rate of dose-limiting toxicities (DLTs) and/or grade 3 or 4 serious adverse events (SAEs) in study participants up to 30 days after the end of protocol therapy. Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
- Change in quantity of CD3+ T-cells in Peripheral Blood and Tumor Tissue [ Time Frame: Baseline, cycle 3, and off-study, an Average of 12 months ]The quantity of CD3+ T-cells in peripheral blood and in tumor biopsies at each timepoint (baseline, cycle 3, and off-study).
- Expression Category of T-cell subsets in Tumor Tissue [ Time Frame: Baseline, cycle 3, and off-study, an Average of 12 months ]The expression category in tumor tissue (none (0%), low (<5%), intermediate (5-50%), or high (>50%) of PD-1, PD-L1, PD-L2, CTLA-4, TIM-3, LAG-3 at each timepoint (baseline, cycle 3, and off-study).
- Absolute Change in T-cell Marker Levels in Peripheral Blood and Tumor Tissue [ Time Frame: Baseline, Cycle 3, Progression, an Average of 12 months ]
The following T cell subsets will be studied in peripheral blood and tumor tissue: (CD4, CD8, T-reg, CTLA4, TIM3, LAG3, memory, naïve, PD-1, Ki67). For each marker, the absolute change in the marker(s) value will be calculated:
- Cycle 3 marker value minus Baseline marker value
- Progression marker value minus Cycle 3 marker value
- Progression marker value minus Baseline marker value
- Description of the Relationship between tumor response according to RECIST 1.1 and tumor response according to alternative radiologic methods [ Time Frame: Baseline, Cycle 3, off-study, an Average of 12 months ]Utilizing each of the alternative (non-RECIST) radiological criteria the investigators will categorize clinical benefit status (CR/PR/SD vs PD). CT and/or MRI with dynamic contrast enhanced sequences will be collected throughout the study at every disease evaluation and analyzed using Choi criteria, MRI volumetrics, and immune-related response criteria. PET/CT will be obtained at baseline, Cycle 3, and off-study and tumor response determined by Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0).
- Change in Quantity of Circulating Tumor Cells (CTCs) in Peripheral Blood [ Time Frame: Baseline, Cycle 3, and Off-study, an Average of 12 months ]The quantity of circulating tumor cells (CTCs) in peripheral blood will be measured at three timepoints: baseline, cycle 3, and off-study.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02636725
|Contact: Breelyn Wilky, MDemail@example.com|
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: Breelyn Wilky, MD 305-243-1287 firstname.lastname@example.org|
|Principal Investigator: Breelyn Wilky, MD|
|Sub-Investigator: Jonathan Trent, MD|
|Principal Investigator:||Breelyn Wilky, MD||University of Miami|