Phase 1b/2 Study of Avelumab With or Without Entinostat in Patients With Advanced Epithelial Ovarian Cancer

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

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