Brief Title
Phase 1b/2 Study of Avelumab With or Without Entinostat in Patients With Advanced Epithelial Ovarian Cancer
Official Title
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
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 patients with refractory or recurrent epithelial ovarian cancer.
Detailed Description
The study is comprised of 2 phases: an open-label Safety Lead-in (Phase 1b) followed by an
Expansion Phase (Phase 2). The Expansion Phase will evaluate the efficacy and safety of
entinostat with avelumab when administered at the Recommended Phase 2 Dose (RP2D) versus
avelumab alone in patients with advanced epithelial ovarian cancer in a randomized,
double-blind, placebo-controlled setting. In Phase 2, patients will be randomized in a 2:1
ratio to receive avelumab plus entinostat or avelumab plus placebo, respectively.
All patients will be assessed at Screening and at specified times during the conduct of the
study using standard clinical and laboratory assessments. Patients will be assessed for
response through radiological assessments. Patients will continue receiving their appropriate
cycles of study treatment until tumor progression or adverse events (AEs) occur which
necessitate discontinuing therapy as determined by the Investigator.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Number of Participants taking 5 mg entinostat weekly in combination with avelumab with Adverse Events as a Measure of Safety and Tolerability
Secondary Outcome
Progression-free survival
Condition
Epithelial Ovarian Cancer
Intervention
entinostat
Study Arms / Comparison Groups
Entinostat plus Avelumab
Description: Avelumab is administered intravenously (IV) on Day 1 of each 14-day cycle in combination with Entinostat administration on D1 and D8 of each cycle at the Maximum tolerated Dose (MTD)/RP2D as determined in the Phase Ib (Dose Determination) part of the study.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
140
Start Date
January 10, 2017
Completion Date
March 2021
Primary Completion Date
July 2019
Eligibility Criteria
Inclusion Criteria:
- 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
- Patient must have acceptable, applicable laboratory requirements
- Patients 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.
Exclusion Criteria:
- 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 patient risk
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Michael Meyers, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02915523
Organization ID
SNDX-275-0603
Responsible Party
Sponsor
Study Sponsor
Syndax Pharmaceuticals
Collaborators
Merck KGaA, Darmstadt, Germany
Study Sponsor
Michael Meyers, MD, PhD, Study Director, Syndax Pharmaceuticals, Inc.
Verification Date
July 2018