The Efficacy and Safety of Niraparib vs Placebo to Treat Breast Cancer in Participants Who Have Tumour DNA in Their Blood After Completing Treatment (ZEST)
- Conditions
- Breast CancerMedDRA version: 23.0Level: PTClassification code 10083232Term: HER2 negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-003973-23-IT
- Lead Sponsor
- GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 800
Participants are eligible to be included in the study
if all following criteria are met:
1.Stage I to III breast cancer per AJCC for breast cancer staging criteria
8th edition with surgical resection of the primary tumor that is
confirmed to be either:
•TNBC,irrespective of BRCA status
•HR+/HER2- BC with a known and documented tBRCA
mutation
2.Completed prior standard therapy for curative intent,including all the following,:neoadjuvant treatment,surgery,adjuvant radiotherapy,and adjuvant chemotherapy
3.Participants with HR+ BC 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.
4.Detectable ctDNA as measured by central Signatera testing.
5.An archival tumour tissue specimen of the primary tumor sufficient in
quality and quantity
( minimum fifteen 5µm sections or 1 FFPE tumur block for ctDNA
assay design and tBRCA testing and minimum 1 FFPE tumur block
for HRD testing)is required.
6.An Eastern Cooperative Oncology Group performance status of
0 or 1.
7.Must be =18 years of age.
8.Must have adequate organ and bone marrow function, as defined
below.If these criteria are not met, randomization and treatment may
be delayed up to 3 weeks.
Absolute neutrophil count:=1,500/µL
Platelets:=100,000/µL
Hemoglobin:=9g/dL or 5.6mmol/L
Serum creatinine:<2×ULN
Total bilirubin:=3×ULN
ALT:=2.5×ULN
Note:complete blood count should be obtained without
transfusion or receipt of colony stimulating factors within 4 weeks prior
to obtaining the sample.Participants with current active liver or biliary
disease are excluded(with the exception of Gilbert's syndrome or
asymptomatic gallstones or otherwise stable chronic liver disease per
Investigator assessment).
9.Participants with toxicity from prior cancer therapy must have
recovered to Grade 1(A participant with Grade 2 neuropathy or Grade 2
alopecia is an exception to this criterion and may qualify for this study.).
Randomization and treatment may be delayed up to 3 weeks to allow for
this criterion to be met.
10.Must be able to swallow and retain orally administered study
treatment.
11.A female participant is eligible if she is not pregnant or breastfeeding,
and at least 1 of the following conditions applies:
•Is not a woman of childbearing potential(WOCBP), as defined in
Appendix 4.
OR
•Is a WOCBP and using a contraceptive method that is highly effective
,as defined in Appendix 4,during the Treatment Period and for at least
180 days after the last dose and agrees not to donate
Eggs for the purpose of reproduction during this period.
The Investigator should evaluate the effectiveness of the contraceptive
method in relationship to the first dose of study treatment.
•A WOCBP must have a negative pregnancy test within 72 hours
before the first dose of study treatment.
•Additional requirements for pregnancy testing are described in Section 8.4.6.
•The Investigator is responsible for review of medical history,menstrual
history,and recent sexual activity to decrease the risk for inclusion of woman with an early undetected pregnancy.
12.Male participants are eligible if they agree to the following during the
Treatment Period and for at least 180 days after the last dose:
•Be abstinent from heterosexual intercourse as their preferred and usual
Life style and agree to
remain abstinent
OR
•Must Agree to use a male condom when having sexual intercourse with a WOCBP who
i
Participants are excluded from the study if any of
following criteria are met:
1.Prior treatment with a PARP inhibitor.
2.Current treatment with a CDK4/6 inhibitor or endocrine therapy other
than anastrozole,letrozole,exemestane,and tamoxifen.
3.Participants have any sign of metastasis or local recurrence after
comprehensive assessment conducted per protocol.
4.Participants have shown no definitive response to preoperative
chemotherapy by pathologic or radiological evaluation,in cases where
preoperative chemotherapy was administered(see Appendix 1).
5.Participants have systolic BP>140mmHg or diastolic BP>90mmHg.
6.Participants have any clinically significant gastrointestinal
abnormalities that may alter absorption such as malabsorption
syndrome or major resection of the stomach and/or bowels.
7.Participants have received colony-stimulating factors(eg, granulocyte
macrophage colony-stimulating factor or recombinant erythropoietin)
within 4 weeks prior to the first dose of study treatment.
8.Participants have previously or are currently participating in a
treatment study of an investigational agent within 4 weeks of the first
dose of therapy preceding the study.
9.Participants have received live vaccine within 30 days of planned start
of study randomization.The use of live
COVID-19adenoviral vaccines within 30 days of randomization must
be discussed with the Medical Monitor.
10.Participants have known hypersensitivity to the components of
niraparib,placebo,or their formulation excipients.
11.Participants have undergone major surgery within 4 weeks of starting
the first dose of study treatment or have not recovered from any effects
of any major surgery.
12.Participants have a second primary malignancy.Exceptions are the
following:
•Adequately treated nonmelanoma skin cancer,curatively treated in situ
cancer of the cervix,ductal carcinoma in situ of the breast,Stage
I Grade 1 endometrial carcinoma
•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
13.Participants have current active pneumonitis or any history of
pneumonitis requiring steroids(any dose)or immunomodulatory
treatment within 90 days of planned start of the study.
14.Participants have any clinically significant concomitant disease or
condition(such as transfusion-dependent anemia or thrombocytopenia)
that could interfere with,or for which the treatment might interfere
with,the conduct of the study or that would,in the opinion of the
Investigator,pose an unacceptable risk to the participants in this study.
15.Participants have any psychological,familial,sociological,or
geographical condition potentially hampering compliance with the study
requirements and/or follow up procedures.Those conditions should be
discussed with the participants before study entry.
16.Participants have high medical risk due to a serious,uncontrolled
medical disorder;nonmalignant systemic disease;or active,uncontrolled
infection(including COVID-19).
17.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.
18.Participants have presence of hepatitis B surface antigen or a positive
hepatitis C antibody test result at Screening or within 3 months prior to
first dose of study treatment.For potent immunosuppressive agents,
partic
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: -Evaluation of the efficacy of niraparib relative to placebo as measured by disease-free survival (DFS);Secondary Objective: -Evaluation of overall survival (OS)<br>-Evaluation of time to progression on next anticancer therapy<br>-Evaluation of distant recurrence-free survival (DRFS)<br>-Evaluation of the safety and tolerability of niraparib <br>-Evaluation of disease-related symptoms that impact participant daily functioning<br>-Evaluation of patient-reported treatment-related symptoms;Primary end point(s): -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, as assessed by Investigator using RECIST v1.1.;Timepoint(s) of evaluation of this end point: -Median DFS for the placebo arm is expected to be ~9 months from randomization.
- Secondary Outcome Measures
Name Time Method