Clinical Trials /

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

NCT03901469

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer
  • Official Title: A Phase 2 Study of ZEN003694 in Combination With Talazoparib in Patients With Triple-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: ZEN003694-004
  • SECONDARY ID: 2018-003906-26
  • NCT ID: NCT03901469

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
ZEN003694Experimental: ZEN003694 in Combination with Talazoparib
TalazoparibExperimental: ZEN003694 in Combination with Talazoparib

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Experimental: ZEN003694 in Combination with TalazoparibExperimentalZEN003694 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
  • ZEN003694
  • Talazoparib

Eligibility 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%
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:A DLT is a treatment-related, clinically significant adverse event or laboratory abnormality occurring during the first cycle of treatment

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Part 1 and Part 2: Evaluate median radiographic progression-free survival
Time Frame:From screening up to 18 months
Safety Issue:
Description:Time to radiographic progression by RECIST 1.1 or death
Measure:Part 1 and Part 2: Evaluate median progression-free survival
Time Frame:From screening up to 12 months
Safety Issue:
Description:Time to radiographic progression by RECIST 1.1, clinical progression, or death
Measure:Part 1 and Part 2: Evaluate duration of response (DOR)
Time Frame:From screening up to 12 months
Safety Issue:
Description:Time from first dose to last dose of ZEN-3694
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Zenith Epigenetics

Trial Keywords

  • TNBC
  • ZEN003694
  • ZEN-3694
  • Talazoparib
  • Breast Cancer
  • PARPi
  • poly ADP ribose polymerase
  • bromodomain
  • BETi

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