Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease (ZEST)

JRCT ID: jRCT2031210330

Registered date:22/09/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Breast cancer
• Date of first enrollment: 28/06/2021
• Target sample size: 40
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,Colombia,Japan,Finland,Japan,France,Japan,Germany,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Mexico,Japan,Netherlands,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,Romania,Japan,Russia,Japan,South Africa,Japan,Spain,Japan,Switzerland,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Cohort1: Participants with tBRCAmut HER2- breast cancer (Independent of HR status including HR+ and TNBC)
Eligible participants will receive either Niraparib or Placebo.

Cohort 2: Participants with tBRCAwt TNBC
Eligible participants will receive either Niraparib or Placebo.

Outcome(s)

Primary Outcome

1.Number of participants with treatment emergent adverse event (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
Time Frame: Up to approximately 34 months
Number of participants with TEAEs, SAEs, and AESIs will be assessed.

2.Number of participants with clinically significant changes in Eastern Co-operative Oncology Group (ECOG) performance status
Time Frame: Up to approximately 34 months
The performance status will be assessed using ECOG scale, where Grade 0 (fully active), Grade 1 (restricted in physically strenuous activity), Grade 2 (ambulatory and capable of all self-care), Grade 3 (capable of only limited self-care) and Grade 4 (completely disabled). Change in ECOG performance from baseline will be assessed.

3.Number of participants with clinically significant changes in relevant laboratory parameters
Time Frame: Up to approximately 34 months
Number of participants with clinically significant changes in hematology and clinical chemistry parameters will be assessed.

4.Number of participants with clinically significant changes in vital signs
Time Frame: Up to approximately 34 months
Number of participants with clinically significant changes in vital signs will be assessed.

5.Number of participants with use of concomitant medications
Time Frame: Up to approximately 34 months
Number of participants using concomitant medications will be assessed.

• Secondary Outcome: Not Applicable

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-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.

Exclude criteria

-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).

Related Information

• Primary Sponsor: Kase Yoichi
• Secondary Sponsor: GlaxoSmithKline
• Secondary ID(s): NCT04915755,2020-003973-23