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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)

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ClinicalTrials.gov Identifier: NCT04915755
Recruitment Status : Recruiting
First Posted : June 7, 2021
Last Update Posted : April 13, 2023
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Neoplasms, Breast Drug: Niraparib Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: This is a double-blind study
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : June 28, 2021
Estimated Primary Completion Date : March 12, 2025
Estimated Study Completion Date : August 28, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort1:Participants with tBRCAmut HER2-breast cancer(Independent of HR status,including HR+andTNBC)
Eligible participants will receive either Niraparib or Placebo.
 Drug: Niraparib
Niraparib will be administered.

Drug: Placebo
Matching placebo will be administered
Experimental: Cohort 2: Participants with tBRCAwt TNBC
Eligible participants will receive either Niraparib or Placebo.
 Drug: Niraparib
Niraparib will be administered.

Drug: Placebo
Matching placebo will be administered


Outcome Measures
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Primary Outcome Measures :
  1. Disease-free survival (DFS) [ Time Frame: Up to 4 years ]
    DFS is defined as the time until disease recurrence, measured from the time of randomization to the earliest date of assessment of disease recurrence or death by any cause.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to 8 years ]
    OS is defined as the time from randomization to the date of death by any cause.

  2. Time to progression on next anticancer therapy (TTP) [ Time Frame: Up to 8 years ]
    Time to progression is defined as the time from randomization to the earliest progression event subsequent to that used for the primary variable DFS or death by any cause.

  3. Distant recurrence-free survival (DRFS) [ Time Frame: Up to 4 years ]
    DRFS is defined as the time from randomization to the first detection of distant metastasis or death by any cause.

  4. Number of participants with Treatment-emergent adverse events (TEAEs), Serious adverse events (SAEs), adverse events of special interest (AESIs), TEAEs leading to death, TEAEs leading to dose modifications and discontinuation [ Time Frame: Up to 8 years ]
    Number of participants with TEAEs, SAEs, AESIs, TEAEs leading to death, TEAEs leading to dose modifications and discontinuation will be summarized.

  5. Number of participants with clinically significant changes in laboratory parameters, vital signs, Eastern Cooperative Oncology Group (ECOG) status, and use of concomitant medications [ Time Frame: Up to 8 years ]
    Number of participants with clinically significant changes in laboratory parameters, vital signs, ECOG status, and use of concomitant medications will be evaluated

  6. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) (Scores on a scale) [ Time Frame: Baseline (Day 1) and up to 8 years ]
    EORTC-QLQC 30 is a 30 item questionnaire developed to assess the quality of life of cancer participants.

  7. Change from Baseline in the Functional Assessment of Cancer Therapy - General Population(FACT-GP5) (Scores on a scale) [ Time Frame: Baseline (Day 1) and up to 8 years ]
    The FACT-GP5 item is a single item from the FACT-G, which assesses how bothersome the side effects of treatment are for participants with cancer.

  8. Patient reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) (Scores on a scale) [ Time Frame: Baseline (Day 1) and up to 8 years ]
    The PRO-CTCAE is a PRO measure developed to evaluate symptomatic toxicity in participants with cancer.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04915755


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04915755    
Other Study ID Numbers: 213831
First Posted: June 7, 2021    Key Record Dates
Last Update Posted: April 13, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Niraparib
Breast cancer susceptibility gene
Human epidermal growth factor-2 negative (HER2)
 Breast cancer
Triple negative breast cancer (TNBC)
Circulating tumor Deoxyribonucleic acid (ctDNA)
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
 Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents