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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03901469
Recruitment Status : Recruiting
First Posted : April 3, 2019
Last Update Posted : December 19, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Zenith Epigenetics

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

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Drug: ZEN003694 Drug: Talazoparib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of ZEN003694 in Combination With Talazoparib in Patients With Triple-Negative Breast Cancer
Actual Study Start Date : June 26, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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
Drug: ZEN003694
Bromodomain Inhibitor

Drug: Talazoparib
PARP Inhibitor




Primary Outcome Measures :
  1. 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 ]
  2. 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

  3. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03901469


Contacts
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Contact: Zenith Study Team 415-470-5600 ZEN003694-004@zenithepigenetics.com

Locations
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United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
United States, Kansas
University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66203
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Tennessee Oncology (Sarah Cannon) Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Belgium
Institut Jules Bordet Recruiting
Brussels, Belgium, 1000
UZ Leuven Recruiting
Leuven, Belgium, 3000
Spain
Vall d'Hebron Institute of Oncology (VHIO) Recruiting
Barcelona, Spain
START Madrid Recruiting
Madrid, Spain
Sponsors and Collaborators
Zenith Epigenetics
Pfizer
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Responsible Party: Zenith Epigenetics
ClinicalTrials.gov Identifier: NCT03901469    
Other Study ID Numbers: ZEN003694-004
2018-003906-26 ( EudraCT Number )
First Posted: April 3, 2019    Key Record Dates
Last Update Posted: December 19, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Zenith Epigenetics:
TNBC
ZEN003694
ZEN-3694
Talazoparib
Breast Cancer
PARPi
poly ADP ribose polymerase
bromodomain
BETi
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents