Predicting Olaparib Sensitivity in Patients With Unresectable Locally Advanced/Metastatic HER2-ne… (NCT05340413) | Clinical Trial Compass
CompletedPhase 2
Predicting Olaparib Sensitivity in Patients With Unresectable Locally Advanced/Metastatic HER2-negative Breast Cancer.
Spain65 participantsStarted 2022-03-25
Plain-language 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.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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.
✓. Patients must be male or female ≥18 years of age at the time of signing the informed consent form.
✓. 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:
✓. 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.
✓
What they're measuring
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)
. 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.
Exclusion criteria
✕. 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:
✕. 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.
✕. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.