EUCTR2018-003906-26-BE进行中（未招募）1 期
A Phase 2 Study of ZEN003694 in Combination with Talazoparib in Patients with Triple-Negative Breast Cancer
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 179
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. Females or males age = 18 years (at time of signing informed consent)
- •2. Parts 1 and 2: Histologically confirmed metastatic or recurrent or locally advanced triple-negative breast cancer (estrogen receptor (ER) =10%; progesterone receptor (PR) =10%; HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH)
- •Expansion: Histologically confirmed metastatic or recurrent, or locally advanced triple-negative breast cancer as defined by the most recent American Society of Clinical Oncology/College of American pathologists (ASCO/CAP) guidelines
- •3. Parts 1 and 2 only: Patient is not a candidate for endocrine based therapy based on Investigator judgement
- •4. Have a history of progressive disease despite prior therapy
- •5. Part 1: Have had at least 1 prior cytotoxic chemotherapy. Part 2: Have had no more than 2 prior chemotherapy-inclusive regimens for locally
- •advanced or metastatic disease, unless approved by the Sponsor (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).
- •Expansion Cohort A (combination treatment in post-TROP2-ADC patients): Have received TROP2-ADC therapy for unresecable locally advanced or metastatic disease.
- •Expansion Cohort B (ZEN003694 monotherapy): Have had at least 1 prior systemic therapy for locally advanced or metastatic disease which may or may not have included TROP2-ADC therapy.
- •Expansion Cohort C (combination treatment in TROP2-ADC-naive patients): Have had at least 1 prior systemic therapy for locally advanced or metastatic disease and who have not received prior TROP2- ADC therapy.
- •6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •7. Part 2 and Expansion only: Measurable disease per RECIST version 1.1
- •8. Adequate laboratory parameters at Screening including:
- •a. Parts 1 and 2: Hemoglobin = 10.0 gm/dL without transfusions during the 4 weeks prior to Screening. Expansion: Hemoglobin = 9.0 gm/dL
- •b. Absolute neutrophil count (ANC) = 1.5 × 109/L
- •c. Platelet count = 150,000/mm3
- •d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.0 x ULN or if liver function abnormalities due to liver metastases AST and ALT = 5.0 x ULN
- •e. Total bilirubin = 1.5 x ULN (= 3.0 x ULN for subjects with known Gilbert's syndrome)
- •f. Calculated (Cockcroft-Gault formula) or measured creatinine clearance = 60 mL/min
- •g. Prothrombin time (PT), international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 x ULN
- •9. Female subjects may be enrolled if they are not of childbearing potential, permanently sterile or who are post-menopausal, defined as no menses for at least 1 year without an alternative medical cause and FSH levels in the post-menopausal range. Female subjects of childbearing potential may be enrolled if they consistently and correctly use a highly effective form of contraception. from the time point of study drug administration until at least 7 months thereafter. Highly effective forms of contraception include: combined (estrogen and progestogen hormonal contraceptives (oral, intravaginal, transdermal) associated with inhibition of ovulation; progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized
排除标准
- •1. Documented germline BRCA1 or BRCA2 mutations
- •2. Parts 1 and 2 only: 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 6 months must have elapsed between the last dose of platinum-based treatment and
- •enrollment.
- •3. Part 2 only: Patients with inflammatory breast cancer (in Part 2 only)
- •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
- •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.
- •6. Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor
- •IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed.
- •7. 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).
- •8. Parts 1 and 2 only: Radiation to >25% of the bone marrow
- •9. Treatment with a bone-targeted radionuclide within 6 weeks of first dose of study drug.
- •10. Have previously received an investigational BET inhibitor (including previous participation in studies with the Sponsor's drug, ZEN003694); except for patients in Expansion Cohort B who received ZEN003694 monotherapy and are eligible to cross-over to combination treatment
- •11. Prior treatment with a PARP inhibitor.
- •12. QTcF interval > 470 msec.
- •13. Insufficient recovery (i.e., has not recovered to at least Grade 1) from prior treatment-related toxicities except for alopecia, fatigue and Grade 2 neuropathy.
- •14. Non-healing wound, ulcer or bone fracture (not including a pathological bone fracture caused by a pre-existing pathological bone
- •15. Parts 1 and 2 only: Brain metastases not adequately treated and clinically stable (at the discretion of the Investigator) for at least 3 months prior to the start of study treatment, unless a shorter interval is approved by the Sponsor's Medical Monitor
- •Expansion only: Progressive, symptomatic, or untreated brain metastases. CNS metastases treated definitively with surgery and/or
- •radiation must be radiographically stable based on imaging at least 3 months after definitive treatment. CNS metastases requiring steroid doses equivalent to prednisone doses >10 mg daily or an increase in steroid doses due to CNS disease prior to consent are not eligible
- •16. Expansion only: Disease initially diagnosed with expression of estrogen receptor (ER) or progesterone receptor (PR) as =5%
- •17. Expansion only: Patients treated with prior endocrine therapy
- •18. Known impaired cardiac function or clinically significant cardiac disease such as uncontrolled supraventricular arrhythmia, ventricular
- •arrhythmia requiring therapy, or congestive heart failure (New York Heart Association functional class III or IV)).
- •19. Myocardial infarction or unstable angina within 6 months prior to the first administration of study drug.
- •20. Known myelodysplastic syndrome.
- •21. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous sy
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