EUCTR2020-003973-23-DE进行中（未招募）1 期
A Randomized Phase 3 Double-Blinded Study Comparing the Efficacy and Safety of Niraparib to Placebo in Participants with Either HER2-Negative BRCA-Mutated or Triple-Negative Breast Cancer with Molecular Disease Based on Presence of Circulating Tumor DNA After Definitive Therapy (ZEST) - Niraparib vs Placebo in Participants with HER2- BRCAmut breast cancer or TNBC with Detectable ctDNA
GlaxoSmithKline Research and Development Ltd.0 个研究点目标入组 800 人开始时间: 2021年5月7日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 800
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Participants are eligible to be included in Cohorts 1 and 2 of the study only if all of the following criteria are met:
- •1.Stage I to III breast cancer per AJCC for breast cancer staging criteria 8th edition with surgical resection of the primary tumor that is confirmed to be either:
- •TNBC, irrespective of BRCA status
- •HR+/HER2- breast cancer with a known and documented deleterious or suspected deleterious tBRCA mutation
- •2.Completed prior standard therapy for curative intent, including all of the following, if indicated: neoadjuvant treatment, surgery, adjuvant radiotherapy, and adjuvant chemotherapy
- •3.Participants with HR+ breast cancer must be on a stable regimen of endocrine therapy, if indicated, for at least 3 months prior to randomization. Ovarian suppression, if indicated, must also have been started at least 3 months prior to randomization.
- •4.Detectable ctDNA as measured by central Signatera testing
- •5.An archival tumour tissue specimen of the primary tumor sufficient in quality and quantity for ctDNA assay design and tBRCA and HRD testing is required. Sponsor requirements for tissue sufficiency are outlined in the Study Reference Manual.
- •6.An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- •7.Must be =18 years of age.
- •8.Must have adequate organ and bone marrow function, as defined below. If these criteria are not met, randomization and treatment may be delayed up to 3 weeks.
- •Absolute neutrophil count:=1,500/µL
- •Platelets:=100,000/µL
- •Hemoglobin:=9 g/dL or 5.6?mmol/L
- •Renal function Calculated creatinine clearance =30 mL/min
- •Total bilirubin:=3×ULN
- •ALT: =2.5×ULN
- •9.Participants with toxicity from prior cancer therapy must have recovered to Grade 1. (A participant with Grade?2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study.) Randomization and treatment may be delayed up to 3 weeks to allow for this criterion to be met.
- •10.Must be able to swallow and retain orally administered study treatment.
- •11.A female participant is eligible if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
- •Is not a woman of childbearing potential (WOCBP), as defined in Appendix 4.
- •Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), as described in Appendix 4, during the Treatment Period and for at least 180 days after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment.
- •A WOCBP must have a negative pregnancy test (highly sensitive urine test or serum test as required by local regulations) within 72 hours before the first dose of study treatment.
- •If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- •Additional requirements for pregnancy testing during and after study treatment are described in Section 8.4.6 of the protocol.
- •The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- •See Appendix 4 for a list of acceptable birth control methods. Information
排除标准
- •Participants are excluded from Cohorts 1 and 2 of the study if any of the following criteria are met:
- •1.Prior treatment with a PARP inhibitor.
- •2.Current treatment with a CDK4/6 inhibitor or endocrine therapy other than anastrozole, letrozole, exemestane, and tamoxifen with or without ovarian
- •suppression.
- •3.Participants have any sign of metastasis or local recurrence after comprehensive assessment conducted per protocol.
- •4.Participants have shown no definitive response to preoperative chemotherapy by pathologic, radiological, or clinical evaluation, in cases where preoperative chemotherapy was administered (see Appendix 1).
- •5.Participants have systolic BP >140 mmHg or diastolic BP >90 mmHg that has not been adequately treated or controlled.
- •6.Participants have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
- •7.Participants have received colony-stimulating factors (eg, granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4?weeks prior to the first dose of study treatment.
- •8.Participants have previously or are currently participating in a treatment study of an investigational agent within 4?weeks of the first dose of therapy preceding the study.
- •9.Participants have received live vaccine within 30 days of planned start of study randomization. Study participants can be vaccinated against Corona virus disease 2019 (COVID-19) using vaccines authorized via the appropriate regulatory mechanisms (i.e. Emergency Use Authorization, Conditional Marketing Authorization or Marketing Authorization Application).
- •10.Participants have known hypersensitivity to the components of niraparib, placebo, or their formulation excipients.
- •11.Participants have undergone major surgery within 4?weeks of starting the first dose of study treatment or have not recovered from any effects of any major surgery.
- •12.Participants have a second primary malignancy. Exceptions are the following:
- •Adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, Stage I Grade 1 endometrial carcinoma
- •Other solid tumors and lymphomas (without bone marrow involvement) diagnosed =5 years prior to randomization and treated with no evidence of disease recurrence and for whom no more than 1 line of chemotherapy was applied
- •13.Participants have current active pneumonitis or any history of pneumonitis requiring steroids (any dose) or immunomodulatory treatment within 90 days of planned start of the study.
- •14.Participants have any clinically significant concomitant disease or condition (such as transfusion-dependent anemia or thrombocytopenia) that could interfere with, or for which the treatment might interfere with, the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable risk to the participants in this study.
- •15.Participants have any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study requirements and/or follow up procedures. Those conditions should be discussed with the participants before study entry.
- •16.Participants have high medical risk due to a serious, uncontrolled medical disorder; nonmalignant systemic disease; or active, uncontrolled infection (including COVID-19). Examples include, but are not limited to, uncontrolled ventricular a
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