Ovarian cancer
Conditions
Interventions
At baseline a biopsie or ascites punction will be done in order to dor the
RECAP test.
Treatment consist of olaparib tablets 300 mg bid oral until disease
progression.
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: For inclusion in the study patients should fulfill the following criteria: 1. Patients with recurrence of high-grade serous or endometrioid EOC (> 3 months after platinum containing chemotherapy and not filling or becoming eligible for platinum based therapy) with the possibility of a tumor biopsy or ascites drainage before starting treatment 2. Diagnosis high grade serous or endometrioid EOC proven histologically. 3. Written Informed Consent Female> / = 18 years Normal organ bone marrow function, known within 28 days for sart olaparib, defined as: B Hb >= 10.0 g / dL, without blood transfusion in the last 28 days Absolute neutrophil number (ANC) >= 1.5 x 109 / L Rom Thrombocytes >= 100 x 109 / L Total bilirubin =51 mL / min Eastern Cooperative Oncology Group (ECOG) performance status 0-2 7. Life expectancy >= 16 weeks. 8. Postmenopausal or evidence of absence of pregnancy for premenopausal / fertile women: negative urine or serum pregnancy test within 28 days of study initiation and before start of treatment on day 1. Postmenopausal is defined as follows: * Amenorrhoea> 1 year, after discontinuation of endocrine therapy Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) values **in the post menopausal range for women under 50 * radiation-induced oophorectomy and last menstrual period> 1 year Otherapy chemotherapy-induced menopause and last menstriuation> 1 year Ster surgical sterilization (bilateral oophorectomy or hysterectomy) 9. Patients want and can be compliant. 10. Evaluable disease (measurable and / or non-measurable) as assessed at baseline using RECIST 1.1 using CT or MRI. 11. For inclusion in i) optional genetic research and ii) optional biomarker study, patients must meet the following criteria: Informed Written informed consent for genetic research * Written informed consent for biomarker research
Exclusion criteria
Exclusion criteria: 12. Participation in another study with a study drug during the past month. 13. Previous treatment with PARP inhibitor, including olaparib. 14. * other malignancy in the past 5 years, with the exception of: adequately treated non-melanoma skin cancer, curative in situ cancer, stage 1 and grade 1 endometrial carcinoma, or other solid tumors including breast cancer and lymphoma (without bone marrow involvement) treated curatively without indication for disease for >=3 years. 15. Radiotherapy within 3 weeks before study treatment. 16. Concomitant use of strong CYP3A inhibitors (eg itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or medium-strong CYP3A inhibitors (eg ciprofloxacin, erconiliazole , verapamil). The required washout period before starting olaparib is 2 weeks. 17. Concomitant use of strong (eg phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or medium CYP3A inducers (eg bosentan, efavirenz, modafinil). The required washout period before starting olaparib 5 weeks for enzalutamide or phenobarbital and 3 weeks for the other products. 18. Persistent toxicity (Common Terminology Criteria for Adverse Event (CTCAE)> -grade 2) from previous anti-tumor therapy, excluding alopecia. 19. Symptomatic uncontrolled brain metastases. stable dosing of corticosteroids is allowed if they have started at least 4 weeks before starting olaparib. Patients with spinal cord compression unless previously treated and clinically stable for 28 days. 20. Major surgery within 2 weeks and patients should have recovered from any effect of any previous surgery. 21. Patients with medical risk based on a seriously uncontrolled medical condition or infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled stroke, unstable or imminent spinal cord injury, superior vena cava syndrome, extensive interstitial lung disease, or any psychiatric illness that hampers informed. 22. Patients unable to take oral medication or with reduced oral absorption. 23. breastfeeding patients. 24. Immune compromised patients. 25. Known hypersensitivity of olaparib or components of the product. 26. Known active hepatitis (eg Hepatitis B or C) 27. Previous allogeneic bone marrow or post-strand transplant. 28. Known myelodysplastic syndromic / acute myeloid leukemia or features suggestive of MDS / AML. 29. Blood transfusion in the past 120 days and platelet transfusion in the past 28 days before starting treatment. 30. Rest ECG with QTc> 470 msec at 2 or more time points within 24 hr or family history with long QT syndrome.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine whether the outcome of the RAD51 assay (HR proficient or HR deficient) correlates with objective response rate (RR according to RECIST 1.1) of olaparib, in patients with recurrent high grade serous or high grade endometrioid EOC. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Compare the descriptive 1 yr PFS of olaparib for the BRCA1 or BRCA2 mutant (germline or somatic) HR deficient group, the non BRCA mutant HR deficient group and the HR proficient group, with HR defined according to the RAD51 assay. • Correlation of RAD51 assay outcomes with overall survival (OS). • Determine percentage of informative RAD51 test results of RAD51 assay in tumor biopsies and/or ascites. • Compare the outcome of the RAD51 assay with the Lynparza 15-gene HRR assay. • Determine grade 3 / 4 toxicity. Exploratory: • Identify molecular markers (including genomic markers in tumor or ascites) that are associated with the outcome of the RAD51 assay. • Explore whether these molecular markers can be measured in liquid biopsies (by analysing ctDNA in blood). | — |
Countries
Netherlands
Outcome results
None listed