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RECRUITINGPhase 3INTERVENTIONAL

Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer

A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant Compared With Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients With BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The primary objective of the study is to measure efficacy of saruparib (AZD5305) plus camizestrant compared with physician's choice CDK4/6i plus ET in patients with BRCA1, BRCA2, or PALB2m, HR-positive, HER2-negative (defined as IHC 0, 1+, 2+/ ISH non-amplified) advanced breast cancer

Who May Be Eligible (Plain English)

Who May Qualify: - Adult females, pre/peri-menopausal and/or post-menopausal, and adult males - Histologically or cytologically documented diagnosis of HR-positive, HER2-negative breast cancer - Advanced breast cancer with either locally advanced disease not amenable to curative treatment or metastatic disease - You should be able to carry out daily activities with 0 level of ability (ECOG 0) or 1 with no deterioration over the previous 2 weeks - FFPE tumour tissue from each participant - Documented germline tumour loss of function mutation in BRCA1, BRCA2, or PALB2 - Adequate organ and marrow function Who Should NOT Join This Trial: - Participants with history of MDS/AML or with features suggestive of MDS/AML - Participants with any known predisposition to bleeding - Any history of persisting severe cytopenia - Any evidence of severe or uncontrolled systemic diseases or active uncontrolled infections - Refractory nausea and vomiting, chronic GI disease, inability to swallow the formulated product, or previous significant bowel resection - History of another primary malignancy - Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy excluding alopecia - Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease - Evidence of active and uncontrolled hepatitis B and/or hepatitis C - Evidence of active and uncontrolled HIV infection - Active tuberculosis infection - Cardiac criteria, including history of arrythmia and cardiovascular disease - Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions - Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * Adult females, pre/peri-menopausal and/or post-menopausal, and adult males * Histologically or cytologically documented diagnosis of HR-positive, HER2-negative breast cancer * Advanced breast cancer with either locally advanced disease not amenable to curative treatment or metastatic disease * ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks * FFPE tumour tissue from each participant * Documented germline tumour loss of function mutation in BRCA1, BRCA2, or PALB2 * Adequate organ and marrow function Exclusion Criteria: * Participants with history of MDS/AML or with features suggestive of MDS/AML * Participants with any known predisposition to bleeding * Any history of persisting severe cytopenia * Any evidence of severe or uncontrolled systemic diseases or active uncontrolled infections * Refractory nausea and vomiting, chronic GI disease, inability to swallow the formulated product, or previous significant bowel resection * History of another primary malignancy * Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy excluding alopecia * Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease * Evidence of active and uncontrolled hepatitis B and/or hepatitis C * Evidence of active and uncontrolled HIV infection * Active tuberculosis infection * Cardiac criteria, including history of arrythmia and cardiovascular disease * Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions * Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study * Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study treatment * Prior treatment with systemic anti-cancer therapy for locoregionally recurrent or metastatic disease is not permitted, apart from treatment with ET up to 28 days before randomisation * Prior treatment within 28 days with blood product support or growth factor support * Any systemic concurrent anti-cancer treatment * Concomitant use of the following types of medications or herbal supplements within 21 days or at least 5 half-lives of randomisation: 1. Strong and moderate CYP3A4 inducers/inhibitors 2. Sensitive CYP2B6 substrates 3. Substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index, eg, warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin. * Concomitant use of drugs that are known to prolong QT and have a known risk of TdP * Systemic use of atropine * The following exclusion criteria apply to treatments administered for early breast cancer: 1. Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy 2. Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer 3. Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting 4. Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.

Treatments Being Tested

DRUG

Saruparib (AZD5305)

Saruparib (AZD5305) is a potent and selective inhibitor of PARP1, with minimal effect on PARP2.

DRUG

Camizestrant

Camizestrant (AZD9833) is an orally bioavailable, next generation SERD with non-clinical and clinical activity in both ESR1 mutant and wild type settings .

DRUG

Abemaciclib

CDK4/6 Inhibitor

DRUG

Ribociclib

CDK4/6 Inhibitor

DRUG

Palbociclib

CDK 4/6 Inhibitor

DRUG

Fulvestrant

Endocrine Therapy

DRUG

Letrozole

Endorcine Therapy

DRUG

Anastrozole

Endocrine Therapy

DRUG

Exemestane

Endocrine Therapy

Locations (20)

Research Site
Gilbert, Arizona, United States
Research Site
Fountain Valley, California, United States
Research Site
Glendale, California, United States
Research Site
Los Angeles, California, United States
Research Site
Newport Beach, California, United States
Research Site
Aurora, Colorado, United States
Research Site
Grand Junction, Colorado, United States
Research Site
Hollywood, Florida, United States
Research Site
Jacksonville, Florida, United States
Research Site
Orlando, Florida, United States
Research Site
Chicago, Illinois, United States
Research Site
Evanston, Illinois, United States
Research Site
Park Ridge, Illinois, United States
Research Site
Urbana, Illinois, United States
Research Site
Winfield, Illinois, United States
Research Site
Indianapolis, Indiana, United States
Research Site
Louisville, Kentucky, United States
Research Site
Baltimore, Maryland, United States
Research Site
Silver Spring, Maryland, United States
Research Site
Silver Spring, Maryland, United States