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)

GlaxoSmithKline (GSK) logo

GlaxoSmithKline (GSK)

Status and phase

Active, not recruiting
Phase 3

Conditions

Neoplasms, Breast

Treatments

Drug: Niraparib
Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT04915755
213831
2020-003973-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

40 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion 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.

Exclusion 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).

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

40 participants in 2 patient groups

Cohort1:Participants with tBRCAmut HER2-breast cancer(Independent of HR status,including HR+andTNBC)
Experimental group
Description:
Eligible participants will receive either Niraparib or Placebo.
Treatment:
Drug: Placebo
Drug: Niraparib
Cohort 2: Participants with tBRCAwt TNBC
Experimental group
Description:
Eligible participants will receive either Niraparib or Placebo.
Treatment:
Drug: Placebo
Drug: Niraparib

Trial contacts and locations

227

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Central trial contact

EU GSK Clinical Trials Call Center; US GSK Clinical Trials Call Center

Data sourced from clinicaltrials.gov

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