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Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Either 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 : October 21, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This is a multicenter, multi-cohort, phase 3, double-blinded, placebo-controlled study to 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. Participants who have completed definitive therapy at any time in the past are eligible for ctDNA monitoring and potential enrollment onto the trial.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a multicenter, multi-cohort, phase 3, double-blinded, placebo-controlled study
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 : February 5, 2025
Estimated Study Completion Date : August 24, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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




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), TEAEs leading to death, and AEs leading to discontinuation [ Time Frame: Up to 8 years ]
    All TEAEs, SAEs, TEAEs leading to death, and AEs leading to discontinuation will be collected.

  5. Number of participants with clinically significant changes in laboratory parameters, vital signs, Eastern Cooperative Oncology Group (ECOG) status, physical examination 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, physical examination and use of concomitant examinations 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: Up to 8 years ]
    The PRO-CTCAE is a PRO measure developed to evaluate symptomatic toxicity in participants with cancer.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 tBRCA mutation.
  • Completed prior standard therapy for curative intent including all of the following, if indicated: neoadjuvant treatment, surgery, adjuvant radiotherapy, and adjuvant chemotherapy.
  • Participants with HR+ breast cancer must be on a stable regimen of endocrine therapy, if indicated, for at least 3 months prior to enrollment. Ovarian suppression, if indicated, must also have been started at least 3 months prior to enrollment.
  • Detectable ctDNA as measured by central Signatera 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).

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.
  • 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 or radiographic evaluation, in cases where preoperative chemotherapy was administered.
  • 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 greater than equal to (>=) 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.
  • Participants have a history of human immunodeficiency virus (HIV) disease.
  • Participants have a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

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
Show Show 57 study locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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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: October 21, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.

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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 Deooxyribonucleic 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