Metastatic Breast Cancer
Conditions
Brief summary
Olaparib, a PARP inhibitor, is proven as an effective therapy for germline BRCA1/2-mutated breast cancer; however, the therapeutic efficacy for somatic mutation in BRCA1/2 or genes of homologous recombination DNA repair is unclear. Maintenance of Oalaprib can delay the disease progression in patients with BRCA1/2 mutated advanced ovarian cancer after treatment with platinum based chemotherapy. The investigators design a phase 2 study to evaluate the efficacy of maintenance of Olaparib in patients with metastatic breast cancer. The investigators enroll patients with metastatic ER(+)Her2(-) or triple-negative breast cancer. Patients who are chemotherapy-naïve or prior 1-line chemotherapy are eligible for screening. All eligible patients will receive 4 cycles of platinum based chemotherapy. Gene test will be performed on their breast tumor. If patients have mutation of HR genes and at least stable disease after platinum based chemotherapy, they will be randomized to treatment arm (Olaparib maintenance) or control arm (continuation of chemotherapy). The primary end-point is progression-free survival, and the secondary end-point is to assess the response rate, overall survival and quality of life.
Interventions
DRUGOlaparib
Olaparib 300mg BID PO
DRUGChemotherapy drug
Continue platinum based chemotherapy
Sponsors
AstraZeneca
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must have a life expectancy ≥ 16 weeks. 2. Provision of informed consent prior to any study specific procedures 3. 20 years of age or older; gender includes female and male 4. ECOG 0-1 5. Patients should be diagnosed as metastatic breast cancer ER(+)Her2(-) or TNBC, diagnosis could be by local hospital 6. HER2 negative \[IHC 0, 1+ or IHC 2+ with corresponding ISH non-amplified of ratio less than 2.0 or ISH nonamplified ratio less than 2.0\] as per ASCO-CAP HER2 guideline recommendations 2013 (ASCO-CAP). 7. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) 8. 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. Postmenopausal is defined at least one of the followings: (a) Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments; (b) Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50; (c) radiation- induced oophorectomy with last menses \>1 year ago; (d) chemotherapy-induced menopause with \>1 year interval since last menses; (f) surgical sterilisation (bilateral oophorectomy or hysterectomy) 9. 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 a highly effective form of contraception (\[see appendix H for acceptable methods\]) if they are of childbearing potential 10. No more than previous 0-1 line of chemotherapy after metastasis confirmed 11. For ER(+) breast cancer, patients should fail at least 1-line of hormone therapy (either in adjuvant setting or in metastatic cancer) before entering this study 12. Patients should undergo 4-cycles of platinum-based chemotherapy and have a CR, PS or SD prior to randomisation. 13. At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging \[MRI\] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1. 14. Patients must have normal organ and bone marrow function measured within 28 days prior to randomisation as defined below: 1. Haemoglobin (Hb) ≥10.0 g/dL 2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 3. Platelet count ≥100 x 109/L 4. Total bilirubin ≤1.5 x institutional upper limit of normal (ULN) unless the patient has documented Gilbert's Syndrome 5. Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN 6. Patients must have creatinine clearance (CrCl) of ≥51 mL/min estimated or measured using standard methodology at the investigating centre (i.e. Cockcroft- Gault, MDRD, CK-EPI, EDTA or 24 hr urine): \-
Exclusion criteria
\- Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CT or MRI assessment | 3 years | Progression-free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survive or death | 3 years | Overall survival rate |
| CT or MRI assessment | 3 years | Response rate |
| Questionnaire | 3 years | Quality of life |
Countries
Taiwan
Contacts
Primary ContactPo-Han Lin
Backup ContactYu-Ting Chiu
Outcome results
None listed