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)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Event (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
研究概览
简要总结
This study will assess the efficacy and safety of Niraparib in participants with either tumor mutation in the BRCA gene (tBRCAmut) HER2- breast cancer (Independent of hormone receptor [HR] status, including HR positive [+] and TNBC) or tumor BRCA wild type (tBRCAwt) TNBC with molecular disease based on the presence of circulating tumor Deoxyribonucleic acid (ctDNA) following surgery or completion of adjuvant therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a double-blind study
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stage I to III breast cancer with surgical resection of the primary tumor that is confirmed to be either: TNBC, irrespective of BRCA status or HR+/HER2- breast cancer with a known and documented deleterious or suspected deleterious tBRCA mutation.
- •Estrogen receptor (ER) and/or progesterone receptor (PgR) negativity is defined as immunohistochemistry (IHC) nuclear staining less than (<) 1 percentage (%), or by Allred scoring system where TNBC is defined to be 0 out of 8 or 2 out of 8, or staining in <1 % of cancer cells.
- •Completed prior standard therapy for curative intent.
- •Participants with HR+ breast cancer must be on a stable regimen of endocrine therapy.
- •Detectable ctDNA as measured by central testing.
- •An archival tumor tissue specimen of the primary tumor sufficient in quality and quantity for ctDNA assay design and tBRCA and Homologous recombination deficiency (HRD) testing is required.
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •Prior treatment with a Poly Adenosine-diphosphate Ribose Polymerase (PARP) inhibitor.
- •Current treatment with a Cyclin-dependent kinase (CDK)4/6 inhibitor or endocrine therapy other than anastrozole, letrozole, exemestane, and tamoxifen with or without ovarian suppression.
- •Participants have any sign of metastasis or local recurrence after comprehensive assessment conducted per protocol.
- •Participants have shown no definitive response to preoperative chemotherapy by pathologic, radiographic or clinical evaluation, in cases where preoperative chemotherapy was administered.
- •Participants have inadequately treated or controlled hypertension.
- •Participants have received live vaccine within 30 days of planned start of study randomization.
- •Participants have a second primary malignancy.
- •Exceptions are the following: (a) Adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal carcinoma in situ (DCIS) of the breast, Stage I Grade 1 endometrial carcinoma. (b) 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.
- •Participant is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and/or for up to 180 days after the last dose of study treatment (except France).
- •Participant is immunocompromised. Participants with splenectomy are allowed. Participants with known human immunodeficiency virus (HIV) are allowed if they meet protocol-defined criteria.
- •Participants have a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
研究组 & 干预措施
Cohort1:Participants with tBRCAmut HER2-breast cancer(Independent of HR status,including HR+andTNBC)
Eligible participants will receive either Niraparib or Placebo.
干预措施: Niraparib (Drug)
Cohort1:Participants with tBRCAmut HER2-breast cancer(Independent of HR status,including HR+andTNBC)
Eligible participants will receive either Niraparib or Placebo.
干预措施: Placebo (Drug)
Cohort 2: Participants with tBRCAwt TNBC
Eligible participants will receive either Niraparib or Placebo.
干预措施: Niraparib (Drug)
Cohort 2: Participants with tBRCAwt TNBC
Eligible participants will receive either Niraparib or Placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Event (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
时间窗: Up to approximately 125 weeks
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, is life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, is a congenital anomaly/birth defect, other situations and is associated with liver injury or impaired liver function. SAEs are subsets of AEs. TEAE is an event that emerged during treatment having been absent pretreatment or worsened relative to the pretreatment state. AESI is any AE (serious or nonserious) that is of scientific and medical concern specific to niraparib for which ongoing monitoring and rapid communication by the Investigator to the Sponsor is warranted. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.
Number of Participants With TEAEs Leading to Death
时间窗: Up to approximately 125 weeks
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is an event that emerged during treatment having been absent pretreatment or worsened relative to the pretreatment state.Number of participants with TEAEs leading to death were reported.
Number of Participants With TEAEs Leading to Dose Modifications and Discontinuation of Study Treatment
时间窗: Up to approximately 125 weeks
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is an event that emerged during treatment having been absent pretreatment or worsened relative to the pretreatment state. Number of participants with TEAEs leading to dose modifications (reduction and interruption/delay) and permanent discontinuation of study treatment were reported.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
时间窗: Up to approximately 125 weeks
Number of participants with ECOG Performance Status was reported and was measured on 6-point grade scale 0: Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Restricted in physically strenuous activity but ambulatory \& able to carry out work of light or sedentary nature; Grade 2 - Ambulatory \& capable of all self-care but unable to carry out any work activities. Up and about more than (\>) 50% of waking hours; Grade 3 -Capable of only limited self-care, confined to bed or chair \> 50% of waking hours; Grade 4 -Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; Grade 5 -Dead. Data is presented as baseline grade, best case on-therapy, and worst-case on-therapy for the available participants.
Number of Participants With Worst-Case Post-Baseline (WCPB) Hematology Results Relative to Baseline
时间窗: Up to approximately 125 weeks
Blood samples were collected for the analysis of hematology parameters. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline is defined as the latest non-missing pre-dose value, including those from unscheduled visits.
Number of Participants With Worst-Case Post-Baseline (WCPB) Clinical Chemistry Results Relative to Baseline
时间窗: Up to approximately 125 weeks
Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented. Baseline is defined as the latest non-missing pre-dose value, including those from unscheduled visits.
Number of Participants With Worst-Case Post-Baseline (WCPB) Vital Signs Results Relative to Baseline
时间窗: Up to approximately 125 weeks
The abnormal vital sign ranges are: Pulse Rate (PR): Low \[\<60 beats per minute (bpm)\], Normal (60 bpm to 100 bpm), High (\>100 bpm); Temperature: Low (\<35 degree Celsius (°C)), Normal (35 C and 38 C), High (\>38 C); Systolic Blood Pressure (SBP): Low (\<90 millimeter of mercury (mmHg)), Normal (\>90 mmHg to \<120 mmHg), High (\>120 mmHg); Diastolic Blood Pressure (DBP): Low (\<60 mmHg), Normal (60 mmHg to 79 mmHg), High (\>80 mmHg). Participants were counted in the maximum worst case increase category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category.
Number of Participants With Use of Concomitant Medications
时间窗: Up to approximately 125 weeks
Number of participants who used concomitant medications is presented.
次要结局
未报告次要终点