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Trial record 1 of 1 for:    NCT02915523
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Phase 1b/2 Study of Avelumab With or Without Entinostat in Patients With Advanced Epithelial Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT02915523
Recruitment Status : Unknown
Verified July 2018 by Syndax Pharmaceuticals.
Recruitment status was:  Active, not recruiting
First Posted : September 27, 2016
Last Update Posted : July 10, 2018
Sponsor:
Collaborators:
Merck KGaA, Darmstadt, Germany
Pfizer
Information provided by (Responsible Party):
Syndax Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE September 14, 2016
First Posted Date  ICMJE September 27, 2016
Last Update Posted Date July 10, 2018
Actual Study Start Date  ICMJE January 10, 2017
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 23, 2016)
  • Number of Participants taking 5 mg entinostat weekly in combination with avelumab with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 months ]
    Phase 1 Dose Determination - Up to 18 patients will be enrolled in this phase of the study which employs a rolling 6 phase 1 design, where six patients must be treated in a dose level and have safety assessed in order to determine the dose-limiting toxicity (DLT) and the MTD and/or RP2D based on entinostat in combination with avelumab
  • Efficacy of entinostat in combination with avelumab at the RP2D versus avelumab plus placebo [ Time Frame: From date of first dose up to 24 months assessed every 6-8 weeks from screening through the end of study (approximately 24 months) ]
    An evaluation of the efficacy of entinostat in combination with avelumab at the RP2D versus avelumab plus placebo, as determined by the duration of Progression-free Survival (PFS) by RECIST1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2016)
  • Progression-free survival [ Time Frame: From date of first dose through date of progression, expected to be 24 months ]
    Assessed by immune response RECIST (irRECIST). PFS is defined as the number of months from the date of the first dose of study drug to the earliest of documented PD or death due to any cause without prior progression.
  • Overall Response Rate [Complete Response (CR) or Partial Response (PR)] [ Time Frame: From date of first dose through date of progression, expected to be approximately 12 months ]
    Assessed by RECIST 1.1 and immune response RECIST (irRECIST) every 6-8 weeks
  • Clinical Benefit Rate [CR or PR, or Stable Disease (SD) for at least 24 weeks] [ Time Frame: From date of first dose through date of progression, expected to be approximately 12 months ]
    Assessed by RECIST 1.1 and irRECIST
  • Overall Survival [ Time Frame: Approximately 36 months from date of first dose. Overall survival is defined as the number of months from date of first dose to the date of death (due to any cause). ]
  • Duration of Response (in patients who experience best overall response of CR or PR) [ Time Frame: From date of first dose through date of progression, expected to be approximately 12 months ]
  • Incidence of treatment-emergent adverse events (TEAES), serious adverse events (SAEs), adverse events resulting in the permanent discontinuation of study drug, and deaths [ Time Frame: 24 months ]
  • Change from baseline in laboratory assessments [ Time Frame: 24 months ]
  • Time to Response (in patients who experience best overall response of CR or PR) [ Time Frame: Approximately 12 months ]
  • Cmax (maximum plasma concentration) of avelumab when given in combination with entinostat [ Time Frame: Pre-dose and post-infusion on Day 1 of Cycles 1 thru 6, then cycles 8, 10, 12, 16, 20, 28, 32, 36, 48, and at the 90-day follow-up (UP TO 24 MONTHS) ]
  • Tmax (time of maximum plasma concentration) of avelumab when given in combination with entinostat [ Time Frame: Pre-dose and post-infusion on Day 1 of Cycles 1 thru 6, then cycles 8, 10, 12, 16, 20, 28, 32, 36, 48, and at the 90-day follow-up (UP TO 24 MONTHS) ]
  • Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) of avelumab when given in combination with entinostat [ Time Frame: Pre-dose and post-infusion on Day 1 of Cycles 1 thru 6, then cycles 8, 10, 12, 16, 20, 28, 32, 36, 48, and at the 90-day follow-up (UP TO 24 MONTHS) ]
  • AUC0-inf (area under the plasma concentration-time curve from 0-time extrapolated to infinity) of avelumab when given in combination with entinostat [ Time Frame: Pre-dose and post-infusion on Day 1 of Cycles 1 thru 6, then cycles 8, 10, 12, 16, 20, 28, 32, 36, 48, and at the 90-day follow-up (UP TO 24 MONTHS) ]
  • t1/2 (elimination half-life and apparent plasma terminal phase elimination rate constant) of avelumab when given in combination with entinostat [ Time Frame: Pre-dose and post-infusion on Day 1 of Cycles 1 thru 6, then cycles 8, 10, 12, 16, 20, 28, 32, 36, 48, and at the 90-day follow-up (UP TO 24 MONTHS) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1b/2 Study of Avelumab With or Without Entinostat in Patients With Advanced Epithelial Ovarian Cancer
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Epithelial Ovarian Cancer
  • Peritoneal Cancer
  • Fallopian Tube Cancer
Intervention  ICMJE
  • Drug: entinostat
    An orally available histone deacetylases inhibitor (HDACi).
    Other Names:
    • SNDX-275
    • MS-275
  • Drug: avelumab
    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.
    Other Name: MSB0010718C
  • Drug: Placebo
    A pill containing no active drug ingredient.
Study Arms  ICMJE
  • Active Comparator: Entinostat plus Avelumab
    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.
    Interventions:
    • Drug: entinostat
    • Drug: avelumab
  • Placebo Comparator: Placebo plus Avelumab
    Avelumab is administered intravenously (IV) on Day 1 of each 14-day cycle in combination with placebo administered on D1 and D8 of each cycle.
    Interventions:
    • Drug: avelumab
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: June 19, 2018)
140
Original Estimated Enrollment  ICMJE
 (submitted: September 23, 2016)
138
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02915523
Other Study ID Numbers  ICMJE SNDX-275-0603
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: 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.
Responsible Party Syndax Pharmaceuticals
Study Sponsor  ICMJE Syndax Pharmaceuticals
Collaborators  ICMJE
  • Merck KGaA, Darmstadt, Germany
  • Pfizer
Investigators  ICMJE
Study Director: Michael Meyers, MD, PhD Syndax Pharmaceuticals, Inc.
Principal Investigator: Ursula Matulonis, MD Dana-Farber Cancer Institute
PRS Account Syndax Pharmaceuticals
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP