Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Randomized Phase 2 Study of Atezolizumab and Entinostat in Patients With aTN Breast Cancer With Phase 1b Lead In

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02708680
Recruitment Status : Completed
First Posted : March 15, 2016
Last Update Posted : May 16, 2022
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Syndax Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 9, 2016
First Posted Date  ICMJE March 15, 2016
Last Update Posted Date May 16, 2022
Actual Study Start Date  ICMJE May 2016
Actual Primary Completion Date March 10, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 2016)
  • Determination of DLT and the MTD and/or RP2D [ Time Frame: In approximately 3 months ]
    Phase 1 Dose Determination - Up to 18 patients will be enrolled in this phase of the study which employs a classical 3+3 design, with the determination of DLT and the MTD and/or RP2D based on entinostat in combination with atezolizumab in C1
  • Duration of Progression-free survival using RECIST 1.1 [ Time Frame: In approximately 1 year ]
    To perform an evaluation of the efficacy of entinostat at the RP2D in combination with atezolizumab in patients with aTNBC, as determined by the duration of progression-free survival (PFS).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2022)
  • Progression-free survival based on immune response RECIST (irRECIST) [ Time Frame: In approximately 1 year ]
    PFS status in each patient. 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 (ORR) based on RECIST 1.1 and irRECIST [ Time Frame: In approximately 1 year ]
    ORR is Complete Response + Partial Response; based on RECIST 1.1 and irRECIST
  • Clinical benefit rate (CBR) based on RECIST 1.1 and irRECIST [ Time Frame: In approximately 1 year ]
    CBR is Complete Response + Partial Response + Stable Disease for at least 24 weeks; based on RECIST 1.1 and irRECIST
  • Overall survival (OS) [ Time Frame: In approximately 2 years ]
    OS status in each patient. OS is defined as the number of months from the first dose of study drug to the date of death due to any cause.
  • Duration of response (DOR) [ Time Frame: In approximately 2 years ]
    In patients with best overall response of CR or PR; number of months from the start date of the response (and subsequently confirmed) to the first date that recurrent disease or PD is documented.
  • Time to response (TTR) [ Time Frame: In approximately 2 years ]
    In patients with best overall response of CR or PR
Original Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2016)
  • Progression-free survival based on immune response RECIST (irRECIST) [ Time Frame: In approximately 1 year ]
    PFS status in each patient. 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 (ORR) based on RECIST 1.1 and irRECIST [ Time Frame: In approximately 1 year ]
    ORR is Complete Response + Partial Response; based on RECIST 1.1 and irRECIST
  • Clinical benefit rate (CBR) based on RECIST 1.1 and irRECIST [ Time Frame: In approximately 1 year ]
    CBR is Complete Response + Partial Response + Stable Disease for at least 24 weeks; based on RECISST 1.1 and irRECIST
  • Overall survival (OS) [ Time Frame: In approximately 2 years ]
    OS status in each patient. OS is defined as the number of months from the first dose of study drug to the date of death due to any cause.
  • Duration of response (DOR) [ Time Frame: In approximately 2 years ]
    In patients with best overall response of CR or PR; number of months from the start date of the response (and subsequently confirmed) to the first date that recurrent disease or PD is documented.
  • Time to response (TTR) [ Time Frame: In approximately 2 years ]
    In patients with best overall response of CR or PR
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomized Phase 2 Study of Atezolizumab and Entinostat in Patients With aTN Breast Cancer With Phase 1b Lead In
Official Title  ICMJE A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 2 Study of Atezolizumab With or Without Entinostat in Patients With Advanced Triple Negative Breast Cancer, With a Phase 1b Lead in Phase
Brief Summary The purpose of this study is to determine the safety and tolerability of entinostat used in combination with atezolizumab in patients with Advanced Triple Negative Breast Cancer (aTNBC). Additionally, the purpose of the study is to assess how effective entinostat and atezolizumab are in combination in patients with aTNBC.
Detailed Description

SNDX-275-0602 is a Phase 1b/2 study evaluating the combination of entinostat plus atezolizumab in patients with aTNBC. The study has 2 phases: an open-label Dose Determination Phase (Phase 1b) followed by an Expansion Phase (Phase 2). The Expansion Phase will evaluate the efficacy and safety of entinostat when administered at the RP2D with atezolizumab in patients with aTNBC in a randomized, double-blind, placebo-controlled setting. Up to 88 evaluable patients are anticipated if the study completes all phases of evaluation (up to 18 patients for Phase 1b, up to 70 patients for Phase 2). Up to 30 study centers in the US and Europe may participate.

Safety will be assessed during the study by documentation of AEs, clinical laboratory tests, physical examinations, vital sign measurements, electrocardiograms (ECGs), and Eastern Cooperative Oncology Group (ECOG) performance status. Adverse events of special interest (AESI) will be collected and reviewed in a manner consistent with serious adverse event reporting procedures.

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 Breast Cancer
Intervention  ICMJE
  • Drug: entinostat
    An orally available histone deacetylases inhibitor (HDAC)
    Other Names:
    • SNDX-275
    • MS-275
  • Drug: atezolizumab
    A humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death ligand 1 (PD-L1).
    Other Name: MPDL3280A
  • Drug: Placebo
    A pill containing no active drug ingredient
Study Arms  ICMJE
  • Active Comparator: Entinostat plus Atezolizumab
    Patients in this arm will receive entinostat at the RP2D in combination with atezolizumab
    Interventions:
    • Drug: entinostat
    • Drug: atezolizumab
  • Placebo Comparator: Placebo plus Atezolizumab
    Patients in this arm will receive placebo in combination with atezolizumab
    Interventions:
    • Drug: atezolizumab
    • 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 Completed
Actual Enrollment  ICMJE
 (submitted: May 9, 2022)
81
Original Estimated Enrollment  ICMJE
 (submitted: March 9, 2016)
88
Actual Study Completion Date  ICMJE March 10, 2021
Actual Primary Completion Date March 10, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Has histologically or cytologically confirmed triple negative breast carcinoma that is either metastatic (stage IV of the TNM classification) or locally recurrent and not amenable to local curative treatment.
  2. Evidence of measurable, locally recurrent or metastatic disease based on imaging studies within 28 days before the first dose of study drug.
  3. Has received at least 1, but no more than 2, prior lines of systemic therapy for locally recurrent and/or metastatic disease.
  4. If patient has a history of treated asymptomatic CNS metastases they are eligible, provided they meet all of the following criteria: Patient has measurable disease outside CNS; Patient does not have metastases to midbrain, pons, medulla or spinal cord; Patient is not on corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed); Patient has not had whole-brain radiation within 6 weeks prior to study enrollment; Patient has stable CNS disease as demonstrated by at least 4 weeks of stability between the last intervention scan and the study screening scan.
  5. ECOG performance status of 0 or 1.
  6. Has acceptable, applicable laboratory parameters.
  7. Female subjects must not be pregnant; willing to use 2 methods of birth control/abstinence if applicable through 120 days after the last dose of study drug.
  8. Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy to Grade <1 (except alopecia or neuropathy).
  9. Able to understand and give written informed consent and comply with study procedures.

Exclusion Criteria:

  1. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  2. Active autoimmune disease including active diverticulitis, symptomatic peptic ulcer disease, colitis, or inflammatory bowel disease that has required systemic treatment in past 2 years.
  3. Previously treated with a PD-1/PD-L1-blocking antibody or a histone deacetylase inhibitor.
  4. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to: History of immune deficiencies or autoimmune disease; Myocardial infarction or arterial thromboembolic events within 6 months prior to screening or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval > 470 msec; Uncontrolled hypertension or diabetes mellitus; Another known malignancy that is progressing or requires active treatment; Active infection requiring systemic therapy; Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  5. Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.
  6. Received a live vaccine within 30 days of the first dose of treatment.
  7. Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to enrollment or who has not recovered from AEs due to mAb agents administered more than 4 weeks earlier.
  8. Prior chemotherapy within 3 weeks, targeted small molecule therapy or radiation therapy within 2 weeks prior to enrollment, or who has not recovered (i.e., ≤Grade 1 at enrollment) from AEs due to a previously administered agent.
  9. Received transfusion of blood products or administration of colony stimulating factors within 4 weeks prior to the first dose of treatment.
  10. Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
  11. Currently receiving treatment with any other agent listed on the prohibited medication list.
  12. If female, is pregnant, breastfeeding, or expecting to conceive starting with the screening visit through 120 days after the last dose of study drug.
  13. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  14. Known active hepatitis B or hepatitis C.
  15. Allergy to benzamide or inactive components of entinostat.
  16. History of allergies to any active or inactive ingredients of atezolizumab.
  17. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
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 Georgia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02708680
Other Study ID Numbers  ICMJE SNDX-275-0602
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.
Current Responsible Party Syndax Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Syndax Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Roche Pharma AG
Investigators  ICMJE
Principal Investigator: Dennis Slamon, MD University of California, Los Angeles
PRS Account Syndax Pharmaceuticals
Verification Date May 2022

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