Study of Avelumab With or Without Entinostat in Participants With Advanced Epithelial Ovarian Cancer
A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 1b/2 Study of Avelumab With or Without Entinostat in Patients With Advanced Epithelial Ovarian Cancer Which Has Progressed or Recurred After First-line Platinum-based Chemotherapy and at Least Two Subsequent Lines of Treatment With a Safety Lead-in
1 other identifier
interventional
140
1 country
12
Brief Summary
The purpose of this study is to determine the biologically active dose of entinostat, when given in combination with avelumab, that is safe and warrants further investigation. Additionally, this study will evaluate the effectiveness of entinostat in combination with avelumab at the determined dose in terms of progression free survival compared to avelumab plus placebo in participants with refractory or recurrent epithelial ovarian cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2016
Longer than P75 for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 14, 2016
CompletedFirst Posted
Study publicly available on registry
September 27, 2016
CompletedStudy Start
First participant enrolled
December 19, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 21, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
April 21, 2021
CompletedResults Posted
Study results publicly available
January 10, 2024
CompletedJanuary 10, 2024
December 1, 2023
2.2 years
September 14, 2016
August 30, 2023
December 19, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase 2: Progression Free Survival (PFS), as Determined by the Local Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
PFS was defined as the number of months from randomization to progressive disease (PD) or death due to any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm); the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions.
From date of randomization to PD or death due to any cause (maximum exposure: 24 cycles [each cycle = 14 days])
Phase 1b: Number of Participants With at Least One Dose Limiting Toxicity (DLT) Adverse Event (AE)
A DLT was defined as the occurrence of any protocol-specified event within the first 2 cycles of treatment (from Cycle 1 Day 1 through the end of Cycle 2) of entinostat in combination with avelumab that were considered by the investigator to be at least possibly related to study drug.
Day 1 through Day 28 (Cycles 1 and 2)
Secondary Outcomes (12)
Phase 1b: Recommended Phase 2 Dose (RP2D)
Day 1 through Day 28 (Cycles 1 and 2)
Phase 2: PFS, as Determined by the Local Investigator Using Immune Response RECIST (irRECIST)
From date of randomization to PD or death due to any cause (maximum exposure: 24 cycles [each cycle = 14 days])
Phase 2: Objective Response Rate (ORR), as Assessed Using RECIST 1.1
From date of randomization to date of progression (maximum exposure: 24 cycles [each cycle = 14 days])
Phase 2: ORR, as Assessed Using irRECIST
From date of randomization to date of progression (maximum exposure: 24 cycles [each cycle = 14 days])
Phase 2: Clinical Benefit Rate (CBR), as Assessed Using RECIST 1.1
From date of randomization to date of progression (maximum exposure: 24 cycles [each cycle = 14 days])
- +7 more secondary outcomes
Study Arms (2)
Entinostat plus Avelumab
ACTIVE COMPARATORAvelumab is administered intravenously (IV) on Day 1 of each 14-day cycle in combination with Entinostat administration on Day 1 and Day 8 of each cycle at the Maximum tolerated Dose (MTD)/RP2D as determined in the Phase Ib (Dose Determination) part of the study.
Placebo plus Avelumab
PLACEBO COMPARATORAvelumab is administered intravenously (IV) on Day 1 of each 14-day cycle in combination with placebo administered on Day 1 and Day 8 of each cycle.
Interventions
An orally available histone deacetylases inhibitor (HDACi).
A fully human antibody of the immunoglobulin (Ig) G1 isotype that targets and blocks Programmed death-ligand 1 (PD-L1), the ligand for Programmed cell death protein 1 (PD-1) receptor.
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer
- Recurrent or progressive disease on or after initial platinum-based chemotherapy
- Evidence of measurable disease based on imaging studies within 28 days before the first dose of study drug
- Previously received at least 3, but no more than 6, lines of therapy including at least 1 course of platinum-based therapy
- Participant must have acceptable, applicable laboratory requirements
- Participants may have a history of brain metastasis provided certain protocol criteria are met
- Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy to Grade ≤1 (except alopecia or neuropathy)
- Able to understand and give written informed consent and comply with study procedures.
You may not qualify if:
- Non-epithelial ovarian carcinomas or ovarian tumors with low malignant potential (i.e., borderline tumors)
- Another known malignancy that is progressing or requires active treatment (excluding adequately treated basal cell carcinoma or cervical intraepithelial neoplasia/cervical carcinoma in situ or melanoma in situ). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years.
- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
- Previously treated with a histone deacetylase inhibitor (i.e., vorinostat, belinostat, romidepsin, panobinostat), PD-1/PD-L1-blocking antibody (i.e., atezolizumab, nivolumab, pembrolizumab), or a cytotoxic T-lymphocyte associated protein-4 (CTLA-4) agent
- Currently enrolled in (or completed) another investigational drug study within 30 days prior to study drug administration
- A medical condition that precludes adequate study treatment or increases participant risk
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Syndax Pharmaceuticalslead
- Merck KGaA, Darmstadt, Germanycollaborator
- Pfizercollaborator
Study Sites (12)
H. Lee Moffitt Cancer Center and Research
Tampa, Florida, 33612, United States
Florida Cancer Specialist East Region (SCRI Affiliate)
West Palm Beach, Florida, 33401, United States
University of Chicago
Chicago, Illinois, 60637, United States
Greater Baltimore Medical Center
Baltimore, Maryland, 21204, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
HCA Midwest Health (SCRI Affiliate)
Kansas City, Missouri, 64131, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19107, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37204, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Kate Madigan, MD, Chief Medical Officer
- Organization
- Syndax Pharmaceuticals, Inc.
Study Officials
- STUDY DIRECTOR
Michael Meyers, MD, PhD
Syndax Pharmaceuticals
- PRINCIPAL INVESTIGATOR
Ursula Matulonis, MD
Dana-Farber Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 14, 2016
First Posted
September 27, 2016
Study Start
December 19, 2016
Primary Completion
February 21, 2019
Study Completion
April 21, 2021
Last Updated
January 10, 2024
Results First Posted
January 10, 2024
Record last verified: 2023-12
Data Sharing
- IPD Sharing
- Will not share
An independent data safety monitoring board (DSMB) will be established for the Phase 2 portion of this study to act in an advisory capacity to the Sponsor with respect to safeguarding the interests of trial patients and assessing the safety of the interventions administered during the trial.