Recurrent epithelial ovarian cancer MedDRA version: 20.0 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Olaparib
Product Name: Olaparib
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with recurrent high grade serous or endometrioid EOC (> 3 months after platinum containing chemotherapy and unwilling or ineligible for platinum based therapy) with a tumor lesion that is amendable for biopsy or who can undergo ascites drainage prior to treatment. treatment. 2. Diagnosis of high grade serous or endometrioid EOC confirmed by histology . 3. Provision of informed consent prior to any study specific procedures 4. Female aged >18 years 5. Patients must have normal organ and bone marrow function measured within 28 days prior to administration olaparib as defined below: ? Haemoglobin = 10.0 g/dL with no blood transfusion in the past 28 days ? Absolute neutrophil count (ANC) = 1.5 x 109/L ? Platelet count = 100 x 109/L ? Total bilirubin = 1.5 x institutional upper limit of normal (ULN) ? Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) = 2.5 x ULN unless liver metastases are present in which case they must be = 5x ULN ? Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of =51 mL/min: Estimated creatinine clearance = (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72 a where F=0.85 for females 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 7. Patients must have a life expectancy = 16 weeks. 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 as: ? Amenorrhoea for > 1 year, following cessation of exogenous hormonal treatments ? Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50 ? radiation-induced oophorectomy with last menses >1 year ago ? chemotherapy-induced menopause with >1 year interval since last menses ? surgical sterilisation (bilateral oophorectomy or hysterectomy) 9. Patients willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. 10. Evaluable disease (measurable and/or non-measurable) that can be accurately assessed at baseline using RECIST 1.1 by CT or MRI and is suitable for repeated assessment (appendix B). 11. For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfil the following criteria: ? Provision of informed consent for genetic research ? Provision of informed consent for biomarker research Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subje
Exclusion criteria
Exclusion criteria: Participation in another clinical study with an investigational product during the last months 13. Any previous treatment with PARP inhibitor, including olaparib. 14. *Other malignancy within the last 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, or other solid tumours including breast cancer and lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for =3 years. 15. Patients receiving radiotherapy y within 3 weeks prior to study treatment. 16. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. 17. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. 18. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) >-grade 2) caused by previous cancer therapy, excluding alopecia. 19. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days. 20. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 21. 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. 22. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 23. Breast feeding women. 24. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). 25. Patients with a known hypersensitivity to olaparib or any of the excipients of the product. 26. Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids 27. Previous allogenic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether the outcome of the RAD51 assay (HR proficient or HR deficient according to RECAP test) correlates with objective response rate (RR according to RECIST 1.1) of olaparib, in patients with recurrent high grade epithelial ovarian cancer.; Secondary Objective: - 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). ; Primary end point(s): response rate according to RECIST 1.1 outcome RAD51 test ; Timepoint(s) of evaluation of this end point: response rate according to RECIST 1.1: every 12 weeks outcome RAD51 test: baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival Toxicity according to NCI-CTC v4.03 criteria ; Timepoint(s) of evaluation of this end point: Overall survival: end of study Toxicity according to NCI-CTC v4.03 criteria: every 4 weeks | — |
Countries
Netherlands
Contacts
Public ContactJudith Kroep
Leiden University Medical Center
Outcome results
None listed