Breast Cancer MedDRA version: 23.0 Level: PT Classification code 10083232 Term: HER2 negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Niraparib
Product Code: [GSK3985771]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Niraparib
CAS Number: 1038915-60-4
Current Sponsor code: GSK3985771
Other descriptive na
Sponsors
GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) -Evaluation of time to progression on next anticancer therapy -Evaluation of distant recurrence-free survival (DRFS) -Evaluation of the safety and tolerability of niraparib -Evaluation of disease-related symptoms that impact participant daily functioning -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
| Measure | Time frame |
|---|---|
| Secondary end point(s): -OS is defined as the time of randomization to the date of death by any cause -Evaluation of time to progression on next anticancer therapy 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. The date of progression will be based on Investigator assessment during or after the next anticancer therapy and will be defined according to local standard clinical practice. Progression may involve any of the following: objective radiological, histopathological, or symptomatic progression or death. -DRFS is defined as the time from randomization to the first detection of distant metastasis or death by any cause as assessed by Investigator either using RECIST v1.1. -Safety and tolerability as measured by the incidence of TEAEs, SAEs, TEAEs leading to death, and AEs leading to discontinuation will be assessed. Clinical laboratory parameters, vital signs, ECOG performance status, physical examinations, and use of concomitant medications will be collected. -Evaluation of disease- and treatment-related symptoms that impact participant daily functioning measured by change from baseline as assessed using the following instruments: EORTC-QLQ-C30 -Evaluation of patient-reported treatment-related symptoms measured by descriptive data presented using items from the PRO-CTCAE and FACT-GP5 ;Timepoint(s) of evaluation of this end point: -Median overall survival for the placebo arm is expected to be ~30 months from randomization; final OS analysis will be ~8 years after the date on which the first participant was randomized. Patient-reported outcomes to assess quality of life will be measured monthly during the trial, at end of treatment, and then post-dose at +30, +90, and +180 days | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed