Last updated: 06/27/2025 12:40:25
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 DiseaseZEST
EudraCT ID
EU CT Number
Not applicable
Trial status
Active, not recruiting
Active, not recruiting
Trial overview
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)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participants with treatment emergent adverse event (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
Timeframe: Up to approximately 34 months
Number of participants with clinically significant changes in Eastern Co-operative Oncology Group (ECOG) performance status
Timeframe: Up to approximately 34 months
Number of participants with clinically significant changes in relevant laboratory parameters
Timeframe: Up to approximately 34 months
Number of participants with clinically significant changes in vital signs
Timeframe: Up to approximately 34 months
Number of participants with use of concomitant medications
Timeframe: Up to approximately 34 months
Secondary outcomes:
Not applicable
Interventions:
Drug: Niraparib
Drug: Placebo
Enrollment:
40
Observational study model:
Not applicable
Primary completion date:
2024-28-06
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms, Breast
Product
Not applicable
Collaborators
NA
Study date(s)
June 2021 to December 2025
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion 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).
Trial location(s)
Location
GSK Investigational Site
Manchester, United Kingdom, M20 4BX
Status
Recruitment Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aire, Argentina, C1426AGE
Status
Study Complete
Location
GSK Investigational Site
Ciudad AutOnoma de Buenos Aire, Argentina, C1015ABO
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma Buenos Aires, Argentina, C1430EGF
Status
Study Complete
Location
GSK Investigational Site
Ciudad de Buenos Aires, Argentina, C1118AAT
Status
Study Complete
Location
GSK Investigational Site
Highlands Ranch, CO, United States, 80045
Status
Study Complete
Location
GSK Investigational Site
Cipoletti Rio Negro, Argentina, R8324CVE
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, PA, United States, 19111
Status
Study Complete
Location
GSK Investigational Site
San Francisco, CA, United States, 94158
Status
Study Complete
Location
GSK Investigational Site
La Jolla, CA, United States, 92093
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Lone Tree, CO, United States, 80045
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New Haven, CT, United States, 06511
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Orange, CA, United States, 92868
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Saint-Petersburg, Russia, 197758
Status
Terminated/Withdrawn
Location
GSK Investigational Site
South Pasadena, CA, United States, 91030
Status
Terminated/Withdrawn
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Active, not recruiting
Actual primary completion date
2024-28-06
Actual study completion date
Not applicable
Plain language summaries
Summary of results in plain language
Available language(s): English, Afrikaans, Dutch (Belgium), Dutch, French (Belgium), French (Canadian), German (Belgium), Italian, Japanese, North Sotho, Polish, Portuguese (Brazil), Southern Ndebele, Southern Sotho, Spanish (Argentina), Spanish, Swati, Tsonga, Tswana, Venda, Xhosa, Zulu
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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