Predicting Olaparib Sensitivity in Patients With Unresectable Locally Advanced/Metastatic HER2-negative Breast Cancer.

NCT05340413 | Completed Phase 2

• 1 other identifier: SOLTI-1910
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objetive is to assess the capacity of the RAD51-foci score to predict the efficacy of olaparib in BRCA1/2, PALB2 or RAD51C/D mut advanced breast cancer (cohort 1). The investigators propose the hypothesis that the RAD51-foci low tumours determined by immunofluorescence using RAD51 assay in patients with BRCA1/2, PALB2 \& RAD51C/D mutation (cohort 1) predicts response to olaparib. Furthermore, The investigators posit that the determination of RAD51-foci score in tumour identifies patients who can benefit from olaparib beyond mutations in these 5 genes. This hypothesis will be tested in cohort 2.

Conditions

HER2-negative Breast Cancer; Metastatic Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Capacity of the RAD51-foci score to predict the efficacy of olaparib in BRCA1/2, PALB2 or RAD51C/D mut advanced breast cancer (cohort 1)

  Overall response rate (ORR) defined as the proportion of patients with best overall response of complete or partial response, as per local investigator´s assessment and according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria in both RAD51-foci low tumours and RAD51-foci high tumours.

  15 months

Secondary Outcomes (5)

• Capacity of the RAD51-foci score to predict the efficacy of olaparib inBRCA1/2, PALB2 or RAD51C/D mut advanced breast cancer (cohort 1) in terms of:

  15 months

• Clinical benefit of olaparib according to the different HRR mutated genes included in the trial in terms of (cohort 1):

  15 months

• Clinical benefit of olaparib in non- HRR-gene mutated or unknown mutational status advanced breast cancer patients, with RAD51-foci low score in terms of (cohort 2):

  15 months

• Capacity of the ctDNA drop after 4 weeks of treatment to predict the efficacy of olaparib in both cohorts in terms of:

  15 months

• Safety and tolerability of olaparib (both cohorts)

  15 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

HER2-negative ABC with documented germline or somatic mutation in BRCA1, BRCA2, PALB2, RAD51C or RAD51D that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Patients with BRCA1, BRCA2, PALB2, RAD51C or RAD51D mutations that are considered to be non-detrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism," etc.) will not be eligible for this cohort.

Drug: Olaparib

Cohort 2

ACTIVE COMPARATOR

HER2-negative ABC with RAD51-foci low score in the most recent locally recurrence or biopsy from the metastatic context and without known or with negative germline or somatic mutations in BRCA1, BRCA2, PALB2, RAD51C or RAD51D predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Mutation status will be assessed in, at least, olaparib responding patients in this subgroup.

Drug: Olaparib

Interventions

Olaparib DRUG

300mg twice daily

Also known as: Lynparza

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• Age
• Patients must be male or female ≥18 years of age at the time of signing the informed consent form.
• Type of patient and disease characteristics
• Histologically or cytologically confirmed breast cancer with evidence of locally advanced disease, not amenable to resection or radiation therapy with curative intent or metastatic disease.
• Patients can have either triple-negative breast cancer (defined as ER and PgR negative (IHC nuclear staining \<1%) and HER2 negative (IHC 0, 1+ or 2+ and/or ISH non-amplified with ratio less than 2.0)) or ER/PgR positive breast cancer, as long as they are HER2 negative and consistent with local standards and most recent ASCO CAP guidelines and:
• Cohort 1: Documented germline or somatic mutation in BRCA1, BRCA2, PALB2, RAD51C or RAD51D that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
• Cohort 2: Unknown or negative germline or somatic mutation in BRCA1, BRCA2, PALB2, RAD51C or RAD51D predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) and RAD51-foci low score in the most recent locally recurrence/metastatic biopsy.
• Patients who have received platinum (cisplatin or carboplatin, either as monotherapy or in combination) for advanced breast cancer are eligible to enter if there has been no evidence of disease progression during the platinum chemotherapy and the pre-screening biopsy for the determination of RAD51-foci score was performed after the end of treatment with the Platinum-based antineoplastic drugs.
• Patients who have received platinum and/or PARP inhibitors as potentially curative treatment for a prior cancer (e.g., ovarian cancer) or as adjuvant/neoadjuvant treatment for breast cancer are eligible provided at least 6 months have elapsed between the last dose of PARP inhibitor or platinum-based treatment and documented evidence of relapse. Note: Patient who relapsed with documented evidence of relapse on/or within 6 months from last dose of PARP inhibitor or platinum-based treatment or who has received PARP inhibitors for advance breast cancer will NOT be included in the study.
• Patients with estrogen and/or progesterone receptor-positive disease must have received and progressed on at least one line of endocrine with/without CDK4/6 therapy (neo/adjuvant or advanced treatment) or have disease that the treating physician believes to be inappropriate for endocrine therapy± CDK4/6 inhibitors.
• At least one measurable lesion that can be accurately assessed at baseline by CT (MRI where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1. (Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.)
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days

You may not qualify if:

• Medical conditions
• Patients with HER2-positive disease as according with the most recent ASCO/CAP guidelines.
• Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) and Stage 1, grade 1 endometrial carcinoma.
• Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTc prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
• Persistent toxicities (\>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
• Patients with symptomatic uncontrolled brain metastases. Participants with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
• Measurable disease outside the CNS is present.
• No evidence of interim CNS progression between the completion of CNS-directed therapy and the screening radiographic study.
• Metastases are limited solely to cerebellar and supratentorial lesions (i.e., no metastases to midbrain, pons, medulla, spinal cord, leptomeningeal metastases or carcinomatosis leptomeningeal).
• Stable requirement for corticosteroids or anticonvulsants as therapy for CNS disease; anticonvulsants or low dose of corticosteroids (≤ 10 mg oral prednisone or equivalent) at a stable dose during \>4 weeks are allowed.
• No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to enrolment.
• No evidence of progression or haemorrhage after completion of CNS directed therapy.
• Patients with spinal cord compression are excluded unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead

Study Sites (5)

H Clinic de Barcelona

Barcelona, Spain

Location

H Vall d Hebron

Barcelona, Spain

Location

H. San Cecilio

Granada, Spain

Location

H. 12 de Octubre

Madrid, Spain

Location

H. C. U. Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Judith Balmaña

  SOLTI Breast Cancer Research Group

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2022
• First Posted: April 22, 2022
• Study Start: March 25, 2022
• Primary Completion: February 3, 2025
• Study Completion: February 3, 2025
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

ES (5)