Recruiting NCT06380751

Saruparib (AZD5305) Plus Camizestrant or Plus Endocrine Therapy, 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

Phase III Interventional Advanced Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Saruparib (AZD5305), Camizestrant, Abemaciclib, Ribociclib.
Who it may be relevant to: Registry conditions: Advanced Breast Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Brazil +24
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant or Plus Endocrine Therapy, 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)

Overview

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

Detailed description

Approximately 4680 participants will be screened to achieve approximately 788 participants randomised to study intervention.

Participants will be randomised in a 2:2:1:2 ratio to one of the following intervention groups:

* Arm 1: saruparib (AZD5305) plus camizestrant * Arm 2: Physician's choice CDK4/6i plus physician's choice ET * Arm 3: Physician's choice CDK4/6i plus camizestrant * Arm 4: Saruparib (AZD5305) plus physician's choice ET

Treatment continues until BICR-confirmed disease progression, unacceptable toxicity occurs, or the participant withdraws consent.

Interventions

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

Primary outcome measures

Progression-Free Survival (Arm 1 vs arm 2) [Time frame: Up to approximately 64 months]

Secondary outcome measures (12)

Progression-Free Survival (arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 64 months]
Overall Survival (arm 1 vs 2, arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 88 months]
Progression Free Survival 2 (arm 1 vs 2, arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 64 months]
Time to chemotherapy (arm 1 vs 2, arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 64 months]
Objective Response Rate (arm 1 vs 2, arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 64 months]
Duration of Response (arm 1 vs 2, arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 64 months]
Participant-reported tolerability (arm 1 vs 2, arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 64 months]
Time to deterioration in patient-reported global health status/QoL as measured by the global health status/QoL scale within the EORTC quality of life questionnaire (QLQ) (arm 1 vs 2, arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 64 months]
Change from baseline in patient-reported global health status/QoL as measured by the global health status/QoL scale within the EORTC quality of life questionnaire (QLQ) (arm 1 vs 2, arm 4 vs 2, arm 1 vs 3, arm 3 vs 2, arm 4 vs 1) [Time frame: Up to approximately 64 months]
Plasma concentrations of saruparib (AZD5305) [Time frame: Up to approximately 64 months]
Plasma concentrations of camizestrant [Time frame: Up to approximately 64 months]
Samples will be used to develop companion diagnostics by analyzing their performance characteristics and calculate their consistency with clinical trial assays used for enrolment onto the study. [Time frame: Up to approximately 64 months]

Eligibility criteria

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 for up to 28 days total 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:

Strong and moderate CYP3A4 inducers/inhibitors
Sensitive CYP2B6 substrates
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:

Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment