Metastatic Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures. For patients aged <20 years and screened in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative. 2. Patients must be =18 years of age. 3. Histologically or cytologically confirmed HER2-ve breast cancer with evidence of metastatic disease. Patients can have either TNBC (defined as oestrogen receptor and progesterone receptor negative [immunohistochemistry nuclear staining <1%] and HER2-ve [immunohistochemistry 0, 1+ or 2+ and/or in situ hybridization non-amplified with ratio less than 2.0]) or oestrogen receptor / progesterone receptor positive breast cancer as long as they are HER2-ve. 4. Documented BRCA1/2 status To be regarded as BRCA1/2 (+ve), the patient must have a mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function). Mutations that are not clearly pathogenic may be assessed by a committee of genetic specialists to adjudicate if the patient is eligible. - Patients with tBRCA mutations: must be confirmed by a validated method (e.g. results from a CLIA certified laboratory or CE-IVD device. 5. Prior treatment with a taxane or an anthracycline in either an adjuvant (may include neoadjuvant) or metastatic breast cancer treatment setting. 6. Patients should have received no more than two prior cytotoxic chemotherapy regimens in the metastatic setting. If a patient has oestrogen receptor and/or progesterone receptor positive HER2 negative metastatic breast cancer and has completed a prior line of hormonal treatment, then if the current or currently planned choice of treatment for the patient does not include a hormonal treatment then they would be a suitable patient to enter the study. Previous endocrine therapy could be in either an adjuvant or a metastatic setting and include endocrine therapy in combination with a targeted agent such as a CDK4/6 or mTOR inhibitor. 7. Be considered suitable, by the Investigator, for further treatment with single-agent chemotherapy for the metastatic disease 8. Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment. 9. Patients must have a life expectancy = 16 weeks 10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1 11. Women of childbearing potential, who are sexually active, must agree to the use of one effective form of contraception and their male partners must use a condom from the signing of the informed consent, throughout the period of taking study treatment and for at least 1 month after last dose of study drug, or they must totally/truly abstain from any form of sexual intercourse. 12. Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use one highly effective form of contraception if they are of childbearing potential. 13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations for greater than 6 months. Are the trial sub
Exclusion criteria
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous enrolment in the present study 3. Exposure to an investigational product (IP) during the last 1 month or 5 half-lives (whichever is longer) prior to enrolment 4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment 5. Any previous treatment with PARP inhibitor, including olaparib 6. 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), Stage 1, grade 1 endometrial carcinoma. 7. Resting 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. 8. Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. 9. 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 olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. 10. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia 11. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML 12. Patients with symptomatic uncontrolled brain metastases. Patients with previously treated stable brain metastases are eligible. Exception: Patients with adequately treated brain metastases documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids (except =10 mg/day prednisone or equivalent for at least 14 continuous days prior to dosing) for management of CNS symptoms are eligible, provided that a repeat CT or MRI following the identification of CNS metastases (obtained at least 2 weeks after definitive therapy) must document adequately treated brain metastases. 13. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery 14. 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. 15. Patients unable to swallow orally
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-world setting through assessment of progression-free survival in germline BRCA mutated patients.;Secondary Objective: To determine the clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-world setting by assessment of overall survival in germline BRCA mutated patients. To determine the clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated patients. To determine the clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated patients. To evaluate the safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-world setting.;Primary end point(s): Progression free survival (PFS), defined as the time from the date of first dose of olaparib to the date of progression as determined by the Investigator (radiological, clinical or symptomatic) or death from any cause (in the absence of progression);Timepoint(s) of evaluation of this end point: Throughout the whole study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Throughout the whole study.;Secondary end point(s): Overall survival, defined as the time from the date of first dose of olaparib to the date of death from any cause. • Time to first subsequent treatment or death (TFST), defined as the time from the date of first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment • Time to second subsequent treatment or death (TSST), defined as the time from the date of first dose of olaparib to the date of second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment • Time to study treatment discontinuation or death (TDT), defined as the time from the date of first dose of olaparib to the date of study treatment discontinuation or death if this occurs before discontinuation of study treatment • Time to second progression or death (PFS2), defined as the time from the date of first dose of olaparib to the date of the earliest progression event (subsequent to that used for the primary variable PFS) or death from any cause • Clinical response rate, defined as the proportion of patients assessed by the Investigator as responding (physician-defined clinical response, radiological [e.g. RECIST] or symptomatic) • Duration of clinical response, defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause (in the absence of progression) Safety • Adverse events/serious adverse events • Collection of clinical chemistry/haematology parameters | — |
Countries
Bulgaria, Canada, China, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed