BRCA mutated platinum-resistant ovarian cancer MedDRA version: 21.1 Level: LLT Classification code 10033131 Term: Ovarian carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Olaparib (Lynparza)
Product Name: Olaparib (Lynparza)
Product Code: AZD2281
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Olaparib
CAS Number: 763113-22-0
Other descriptive name:
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be eligible for inclusion in this study if all of the following criteria apply. 1. Female patients, aged 16+ years with relapsed epithelial ovarian, primary peritoneal or fallopian tube cancer who have relapsed within 12 months of previous platinum-based therapy. Their most recent chemotherapy does not have to have been platinum-based. 2. Patients can have received prior PARP inhibitor and antiangiogenic therapy, but there must be a > 6 month interval since treatment. 3. Patients can have received prior antiangiogenic therapy, but there must be a > 6 month interval since treatment; except for bevacizumab where a 6 week interval is required. 4. Measurable disease by RECIST Version 1.1 performed in past 4 weeks. 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) and which is suitable for accurate repeated measurements. 5. Sufficient archival tissue confirming histological diagnosis available. 6. ECOG PS 0-2 7. Able to swallow and retain oral medications. 8. Life expectancy > 12 weeks in terms of disease related mortality 9. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 10. Written (signed and dated) informed consent prior to any study specific procedures and be capable of co-operating with protocol. 11. Patients must have • Haemoglobin = 9.0 g/dL and no blood transfusions in the 28 days prior to randomisation 12. Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below: • 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) • AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be = 5x ULN • Serum creatinine = 1.5 x institutional upper limit of normal (ULN) or calculated creatinine clearance >50 ml/min calculated using Cockroft-Gault, Jelliffe or Wright (see Appendix 4) • Urine dipstick for proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: A patient will not be eligible for the trial if any of the following apply: 1. Received previous single agent weekly paclitaxel for relapsed disease. 2. Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used during the trial and for 6 months after stopping treatment. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. Pregnancy test will be performed monthly in women of child bearing potential. 4. Radiotherapy within 2 weeks from the last dose prior to study treatment 5. Started a stable dose of bisphosphonates for bone metastases less than 4 weeks prior to treatment with study drug e.g. patient is eligible and can continue to take bisphosphonates if these were started at least 4 weeks prior to treatment with study drug. 6. Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. 7. Concomitant use of potent inducers of CYP3A4 such as rifampicin, carbamazepine, phenobarbital, phenytoin and St. John Wort. 8. Persistent toxicities (>=CTCAE grade 2), with the exception of alopecia, caused by previous cancer therapy. 9. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. 10. Blood transfusions within 1 month prior to study start 11. Patients with myelodysplastic syndrome/acute myeloid leukaemia. 12. Patients with symptomatic, untreated, uncontrolled brain or meningeal metastases or tumour. a. A scan to confirm the absence of brain metastases is not required. b. Patients with radiological evidence of stable brain metastases are eligible, providing that they are asymptomatic and: i. Do not require corticosteroids, or ii. Have previously been treated with corticosteroids, with clinical and radiological evidence of stabilisation at least 10 days after discontinuation of steroids iii. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment. 13. Major surgery within 14 days of starting study treatment 14. Patients who have not recovered from any effects of any major surgery. 15. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. 16. Any psychiatric disorder that prohibits obtaining informed consent. 17. Left Ventricular Ejection Fraction (LVEF) 150/100mmHg, either systolic or diastolic or both, despite anti-hypertensive medication) 19. History of inflammatory bowel disease 20. History of cerebrovascular accident (including transient ischaemic attacks) within last 12 months. 21. Gastro intestinal impairment that could affect ability to take, or absorption of, oral medicines including sub- acute or complete bowel obstruction 22. Evidence of severe or uncontrolled cardiac disease 23. Evidence of active bleeding or bleeding diathesis. Defined as significant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to assess the efficacy of olaparib compared to weekly paclitaxel or the combination of olaparib and cediranib in patients with platinum resistant ovarian cancer.;Secondary Objective: Secondary objectives: * Safety and tolerability of the combiBRCA mutated onation of olaparib and cediranib in patients with platinum resistant ovarian cancer * Overall Survival * Objective Response Rate * Quality of life in patients receiving olaparib compared to weekly paclitaxel or the combination of olaparib and cediranib. Tertiary Objectives: * Translational research (identification of potential biomarkers of response);Primary end point(s): Progression free survival (PFS);Timepoint(s) of evaluation of this end point: Every 8 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Adverse events using CTCAE v4.03 2. Overall survival 3. Objective response rate based on RECIST v1.1 and GCIG CA125 criteria 4. Quality of Life Outcomes based on EQ5D, EORTC-QLQ C30 and OV28;Timepoint(s) of evaluation of this end point: 1. Every visit 2. 12 & 18 months post randomisation 3. Every 8 weeks 4. Baseline, then Day 1 of each cycle, and end of treatment visit | — |
Countries
United Kingdom
Contacts
Public ContactNaomi McGregor
Oncology Clinical Trials Office (OCTO)
Outcome results
None listed