NIRAPARIB TOSILATE MONOHYDRATE for HER2-negative BRCA-mutated breast cancer | Triple-negative breast cancer

Inclusion criteria

• {"criterion_text":"- Stage I-III breast cancer (BC) per AJCC for BC staging criteria 8th edition with surgical resection of the primary tumor that is confirmed to be either: •TNBC •HR+/HER2− breast cancer with a known and documented deleterious or suspected deleterious tBRCA mutation (either sBRCA or gBRCA positive)\n- \"Must be able to swallow and retain orally administered study treatment \"\n- \"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) OR •Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), during the Treatment Period and for at least 180 days after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) 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 (highly sensitive urine test or serum test as required by local regulations) within 72 hours before the first dose of study treatment. •If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. •Additional requirements for pregnancy testing during and after study treatment are described in Section 8.4.6 of the protocol. •The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. \"\n- \"Male participants are eligible if they agree to the following during the Treatment Period and for at least 90 days after the last dose of study treatment: •Be abstinent from intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR •Must agree to use contraception/barrier as detailed below: Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) PLUS •Male participants must refrain from donating sperm for at least 90 days after the last dose of study treatment \"\n- \"Must be able to understand the study procedures and agree to participate in the study by providing written informed consent) of the protocol. \"\n- \"Completed prior standard therapy for curative intent, including all of the following, if indicated: neoadjuvant treatment, surgery, adjuvant radiotherapy, and adjuvant chemotherapy \"\n- \"Participants with HR+ breast cancer must be on a stable regimen of endocrine therapy, if indicated, for at least 3 months prior to randomization. Ovarian suppression, if indicated, must also have been started at least 3 months prior to randomization. \"\n- \"Detectable ctDNA as measured by central testing. As of the date of the decision to stop enrollment, sample collection was stopped \"\n- \"An archival tumour tissue specimen of the primary tumor sufficient in quality and quantity for ctDNA assay design and tBRCA and HRD testing is required \"\n- \"An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 \"\n- Must be ≥18 years of age\n- \"Must have adequate organ and bone marrow function, as defined below. Absolute neutrophil count:≥1,500/μL Platelets:≥100,000/μL Hemoglobin:≥9 g/dL or 5.6 mmol/L Renal function Calculated creatinine clearance ≥30 mL/min Total bilirubin:≤3×ULN ALT: ≤2.5×ULN \"\n- \"Participants with toxicity from prior cancer therapy must have recovered to Grade 1. (A participant with Grade 2 neuropathy or any grade of alopecia is an exception to this criterion and may qualify for this study.) \""}

Exclusion criteria

• {"criterion_text":"- \"Prior PARP inhibitor treatment \"\n- \"Participants have known hypersensitivity to the components of niraparib, placebo, or their formulation excipients \"\n- \"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 \"\n- \"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 (DCIS) 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 \"\n- \"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 \"\n- \"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. \"\n- \"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 \"\n- \"Participants have high medical risk due to a serious, uncontrolled medical disorder; nonmalignant systemic disease; or active, uncontrolled infection (including COVID-19). Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, active uncontrolled coagulopathy, bleeding disorder, or any psychiatric disorder that prohibits obtaining informed consent. \"\n- \"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 \"\n- \"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. Participants with presence of hepatitis B core antibody should also be excluded \"\n- \"Participant is immunocompromised. Participants with splenectomy are allowed. Participants with known human immunodeficiency virus (HIV) are allowed if they meet the required criteria (refer to study protocol) \"\n- \"Current treatment with a CDK4/6 inhibitor or endocrine therapy other than anastrozole, letrozole, exemestane, and tamoxifen with or without ovarian suppression \"\n- \"Participants have a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) \"\n- \"Participants have any sign of metastasis or local recurrence after comprehensive assessment conducted per protocol \"\n- \"Participants have shown no definitive response to preoperative chemotherapy by pathologic, radiological, or clinical evaluation, in cases where preoperative chemotherapy was administered \"\n- \"Participants have systolic BP >140 mmHg or diastolic BP >90 mmHg that has not been adequately treated or controlled \"\n- \"Participants have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels \"\n- \"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 \"\n- \"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 \"\n- \"Participants have received live vaccine within 30 days of planned start of study randomization. Study participants can be vaccinated against Corona virus disease 2019 (COVID-19) using vaccines authorized via the appropriate regulatory mechanisms (i.e. Emergency Use Authorization, Conditional Marketing Authorization or Marketing Authorization Application) \""}

Primary endpoints

• {"endpoint_text":"- \"Primary End Point - The incidence of TEAEs, SAEs, and AESIs; TEAEs leading to death, TEAEs leading to dose modifications, and TEAEs leading to discontinuation will be assessed. Clinically relevant laboratory parameters, vital signs, ECOG performance status, and use of concomitant medications will be collected and evaluated as defined in the Statistical Analysis Plan (SAP)\"","definition_or_measurement_approach":"Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs); TEAEs leading to death, dose modifications, and discontinuation. Clinically relevant laboratory parameters, vital signs, ECOG performance status, and concomitant medication use will be collected and evaluated as defined in the Statistical Analysis Plan (SAP)."}

Italy

Earliest CTIS Part Ii Submission Date

15-07-2024

Latest Decision Or Authorization Date

12-08-2024

Processing Time Days

28

Number Of Sites

1

Number Of Participants

54

Spain

Earliest CTIS Part Ii Submission Date

15-07-2024

Latest Decision Or Authorization Date

05-08-2024

Processing Time Days

21

Number Of Sites

10

Number Of Participants

40

Netherlands

Earliest CTIS Part Ii Submission Date

15-07-2024

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

633

Number Of Sites

1

Number Of Participants

20

Poland

Earliest CTIS Part Ii Submission Date

15-07-2024

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

624

Number Of Sites

1

Number Of Participants

29

Primary sponsor

Full Name

Glaxosmithkline Research & Development Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Sermes CRO

Responsibilities

patient fee reimbursement

Name

Iqvia Biotech Limited

Responsibilities

code: 7

Third parties

• {"country":"Poland","full_name":"Komtur Polska Sp. z o.o.","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"code: 7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long term storage of samples","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Sermes CRO","duties_or_roles":"patient fee reimbursement","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Natera Inc.","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Poland","full_name":"Let Me Pay Sp. z o.o.","duties_or_roles":"Patient fee reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"Medicine product destruction","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"kit preparation / distribution; Sample storage and tracking; interim storage","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Myriad Genetics Inc.","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}