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A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer (TNBC)

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: NCT03901469
Recruitment Status : Active, not recruiting
First Posted : April 3, 2019
Last Update Posted : July 13, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Zenith Epigenetics

Tracking Information
First Submitted Date  ICMJE March 22, 2019
First Posted Date  ICMJE April 3, 2019
Last Update Posted Date July 13, 2021
Actual Study Start Date  ICMJE June 26, 2019
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • Part 1 and Part 2: Incidence of of treatment-related adverse events (AE) and treatment-related serious adverse events (SAE) [ Time Frame: From screening up to 18 months ]
  • Part 1: Incidence of dose-limiting toxicities (DLT) [ Time Frame: Cycle 1, Up to 1 month ]
    A DLT is a treatment-related, clinically significant adverse event or laboratory abnormality occurring during the first cycle of treatment
  • Part 2: Objective response rate (ORR) defined as a complete response (CR), partial response (PR) or stable disease (SD ≥ 4 cycles) by RECIST 1.1 [ Time Frame: From screening up to 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • Part 1 and Part 2: Measure the pharmacokinetic (PK) parameter: AUC of ZEN003694 administered in combination with talazoparib [ Time Frame: From screening up to 6 months ]
  • Part 1 and Part 2: Measure the pharmacokinetic (PK) parameter: Cmax of ZEN003694 administered in combination with talazoparib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 2 Day 15 ]
  • Part 1: Measure the pharmacokinetic (PK) parameter: Cmin of ZEN003694 administered in combination with talazoparib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 2 Day 15 ]
  • Part 1 and Part 2: Measure the pharmacokinetic (PK) parameter: Tmax of ZEN003694 administered in combination with talazoparib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 2 Day 15 ]
  • Part 1 and Part 2: Measure the pharmacokinetic (PK) parameter: t1/2 of ZEN003694 administered in combination with talazoparib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 2 Day 15 ]
  • Part 1: Objective response rate (ORR) defined as a complete response (CR), partial response (PR) or stable disease (SD ≥ 4 cycles) by RECIST 1.1 [ Time Frame: From screening up to 6 months ]
  • Part 1 and Part 2: Evaluate median radiographic progression-free survival [ Time Frame: From screening up to 18 months ]
    Time to radiographic progression by RECIST 1.1 or death
  • Part 1 and Part 2: Evaluate median progression-free survival [ Time Frame: From screening up to 12 months ]
    Time to radiographic progression by RECIST 1.1, clinical progression, or death
  • Part 1 and Part 2: Evaluate duration of response (DOR) [ Time Frame: From screening up to 12 months ]
    Time from first dose to last dose of ZEN-3694
  • Part 1 and Part 2: Change From Baseline in Global Health Status/Quality of Life (QoL) Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) for Overall Duration [ Time Frame: Screening and Day 1 of every 28-day Cycle, up to 18 months (Overall Duration) ]
    EORTC QLQ-C30: cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each question assessed on 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much); functional scales: higher score = better level of functioning; symptom scale: higher score = more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1= very poor to 7= excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.
  • Part 1 and Part 2: Change from Baseline in Breast Symptoms Scale as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) [ Time Frame: Screening and Day 1 of every 28-day Cycle, up to 18 months (Overall Duration) ]
    EORTC-QLQ-BR23 is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much), higher scores=high level of symptom/problems.
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 A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer
Official Title  ICMJE A Phase 2 Study of ZEN003694 in Combination With Talazoparib in Patients With Triple-Negative Breast Cancer
Brief Summary This is two-part open label, non-randomized, Phase 2, study of ZEN003694 in combination with Talazoparib in patients with TNBC without germline mutations of BRCA1 or BRCA2. Part 1 is dose escalation and Part 2 is a Simon 2-Stage design
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Cancer
Intervention  ICMJE
  • Drug: ZEN003694
    Bromodomain Inhibitor
  • Drug: Talazoparib
    PARP Inhibitor
Study Arms  ICMJE Experimental: Experimental: ZEN003694 in Combination with Talazoparib
ZEN003694 will be administered orally once daily with Talazoparib orally once daily in 28-day cycles, enrolling TNBC patients. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2
Interventions:
  • Drug: ZEN003694
  • Drug: Talazoparib
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 1, 2019)
49
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Females or males age ≥ 18 years (at time of signing informed consent)
  2. Histologically confirmed metastatic or recurrent triple-negative breast cancer (estrogen receptor (ER) ≤10%; progesterone receptor (PR) ≤10%; HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH)
  3. Part 1: Progressed on at least 1 prior cytotoxic chemotherapy at least 21 days prior to the start of study treatment. Part 2: Progressed on no more than 3 prior chemotherapy-inclusive regimens for locally advanced or metastatic disease (no limit on prior targeted anticancer therapies such as mechanistic target or rapamycin (mTOR) or CDK4/6 inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against CTL4 or VEGF) at least 21 days prior to the start of study treatment.
  4. Patient is not a candidate for endocrine based therapy or has progressed on at least 2 prior endocrine based therapies in the locally advanced or metastatic setting
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  6. Part 2 only: Measurable disease per RECIST version 1.1

Exclusion Criteria

  1. Documented germline BRCA1 or BRCA2 mutations
  2. Evidence of disease progression during platinum treatment either in the neoadjuvant or in the metastatic setting. For patients receiving platinum in the neoadjuvant setting, at least 12 months must have elapsed between the last dose of platinum-based treatment and enrollment.
  3. Patients with inflammatory breast cancer
  4. Current or anticipated use of medications known to be strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows. Strong inhibitors, inducers or substrates must be discontinued at least 7 days prior to the first administration of study drug.
  5. Current or anticipated use within 7 days prior to the first administration of study drug, or during the study, of strong P-gp inhibitors. For a list of strong P-gp inhibitors, refer to Section 8.4.1.
  6. Prior anticancer therapy (chemotherapy, radiation, hormone therapy, immunotherapy or investigational agent) within 3 weeks from the start of study drug (except for nitrosoureas and mitomycin C within 6 weeks from start of study drug).
  7. Have not progressed on prior endocrine therapy and have an ER and/or PR ≥ 1%
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
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 Belgium,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03901469
Other Study ID Numbers  ICMJE ZEN003694-004
2018-003906-26 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zenith Epigenetics
Study Sponsor  ICMJE Zenith Epigenetics
Collaborators  ICMJE Pfizer
Investigators  ICMJE Not Provided
PRS Account Zenith Epigenetics
Verification Date July 2021

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