A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer (TNBC)
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| ClinicalTrials.gov Identifier: NCT03901469 |
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Recruitment Status :
Recruiting
First Posted : April 3, 2019
Last Update Posted : October 5, 2020
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Sponsor:
Zenith Epigenetics
Collaborator:
Pfizer
Information provided by (Responsible Party):
Zenith Epigenetics
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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 |
| 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 2021 |
| Estimated Study Completion Date : | January 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
Drug Information available for:
Talazoparib
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: ZEN003694
Bromodomain Inhibitor Drug: Talazoparib PARP Inhibitor |
Primary Outcome Measures :
- 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 ]
Secondary Outcome Measures :
- 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.
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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:
- Females or males age ≥ 18 years (at time of signing informed consent)
- 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)
- 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.
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Part 2 only: Measurable disease per RECIST version 1.1
Exclusion Criteria
- Documented germline BRCA1 or BRCA2 mutations
- 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.
- Patients with inflammatory breast cancer
- 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.
- 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.
- 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).
- 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
| Contact: Zenith Study Team | 415-470-5600 | ZEN003694-004@zenithepigenetics.com |
Locations
| 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
| 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: | October 5, 2020 |
| Last Verified: | October 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Zenith Epigenetics:
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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 |