Olaparib+Trastuzumab in HER2[+],Breast Cancer Susceptibility Gene (BRCA) Mutated Advanced Breast Cancer

NCT03931551 | Terminated Phase 2 DMC

• 2 other identifiers: MedOPP1682018-001213-32
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multicenter, open-label, single-arm, phase II clinical trial, phase II trial will evaluate the efficacy and safety of olaparib plus trastuzumab in patients with HER2\[+\], BRCA-mutated advanced breast cancer

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Assess the efficacy of olaparib in combination with trastuzumab

  as determined by the Clinical benefit rate (CBR) response (PR) divided by the number of patients in the analysis set- in patients with germinal BRCA-mutated \[cohort A\] based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria guidelines v.1.1.

  Baseline up to 12 months.

Secondary Outcomes (8)

• ORR

  Baseline up to 30 months.

• PFS i

  Baseline up to 30 months.

• Clinical benefit rate (CBR

  Baseline up to 30 months.

• Duration of response (DoR)

  From documented objective response up to 30 months.

• Maximum Tumor Shrinkage

  Baseline up to 30 months.

Other Outcomes (2)

• Exploratory Objective (prevalence of BRCA alterations)

  Baseline up to 30 months.

• Exploratory Objective (predictive value of BRCA alterations)

  Baseline up to 30 months.

Study Arms (1)

Interventional Arm

EXPERIMENTAL

Olaparib tablet 300mg bd po + Herceptin (IV 4 mg/kg body followed by weekly doses of 2 mg/kg, or SC 600 mg every 3 weeks) until progression or unacceptable toxicity.

Drug: Olaparib [Lynparza®] plus Trastuzumab [Herceptin®]

Interventions

Olaparib [Lynparza®] plus Trastuzumab [Herceptin®] DRUG

Participants will receive olaparib (300 mg tablets, orally twice daily during 21-day cycles) in combination with herceptin (intravenous dose of 4 mg/kg body weight with subsequent weekly doses of 2 mg/kg or subcutaneous dose of 600 mg every 3 weeks) until progression or unacceptable toxicity.

Also known as: Lynparza®; Herceptin®

Interventional Arm

Eligibility Criteria

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

You may qualify if:

• Obtention and signing of the molecular preselection consent regarding the mutational BRCA status confirmation prior to provision of the informed consent.
• Provision of informed consent prior to any study specific procedures.
• Male or female ≥18 years of age at the time of signing the Informed Consent Form (ICF).
• Histologically and/or cytologically confirmed breast cancer with evidence of advanced disease (locoregionally recurrent or metastatic) not amenable to resection or radiation therapy with curative intent.
• Patients with histologically and/or cytologically locally confirmed diagnosis of Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) May 2018 criteria.
• Patients with documented germinal mutation in Breast Cancer (BRCA)1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Patients with germinal BRCA1/2 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 the study. Patients with known germinal BRCA status prior to enrollment are considered eligible to participate.
• Criteria of resistance to trastuzumab defined as:
• Relapse on (neo) adjuvant treatment or within 6 months from completion, or
• Progression on a trastuzumab regimen for advanced disease. No limitations on the number of prior trastuzumab regimens.
• At least one prior systemic regimen for advanced disease including a pertuzumab or T-DM1 based regimen. No limitations on the number of prior systemic regimens.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1.
• Life expectancy greater or equal to 16 weeks.
• Patients must have evaluable or measurable disease by Computed Tomography (CT) scan or Magnetic resonance imaging (MRI), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Patients must have normal organ and bone marrow function within 35 days prior to administration of study treatment as defined below:
• Hematological: White blood cell (WBC) count \>3.0 x 109/L, absolute neutrophil count (ANC) ≥1.5 x 109/L, platelet count ≥100.0 x109/L, and hemoglobin ≥ 10 g/dL

You may not qualify if:

• Patients that have previously received any poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) for any reason, including olaparib.
• Involvement in the planning and/or conduct of the study (applies to both Sponsor's staff and/or staff at the study site).
• Patients simultaneously enrolled in any interventional clinical trial.
• Patients who have received any systemic chemotherapy during the last 3 weeks prior initiating protocol therapy.
• Patients who have had radiation therapy encompassing \>20% of the bone marrow within 3 weeks prior to start of treatment, excepting for palliative radiation therapy to a small field \>1-week prior to Day 1 of study.
• Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
• Concomitant use of known strong Cytochrome P450 (CYP)3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, boosted protease inhibitors, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Persistent toxicities (Common Terminology Criteria for Adverse Events (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
• Patients with Myelodysplastic syndrome (MDS) / Acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
• Patients having diagnosis, detection, or treatment of another type of cancer during the last 5 years prior to initiating protocol therapy (except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, definitively treated ductal carcinoma in situ, stage 1, grade 1 endometrial carcinoma), or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≤5 years).
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Patients considered a high 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 6 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution CT 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.
• Immunocompromised patients (e.g., patients who are known to be serologically positive for human immunodeficiency virus and those with undetectable viral load).

Sponsors & Collaborators

• MedSIR: lead

Study Sites (4)

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

MeSH Terms

Interventions

olaparib; Trastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jose Enrique Alés-Martínez

  Complejo Hospitalario de Ávila

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: April 30, 2019
• Study Start: April 30, 2019
• Primary Completion: March 2, 2022
• Study Completion: March 2, 2022
• Last Updated: February 22, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)