Relapsed high grade serous ovarian (fallopian tube, primary peritoneal) carcinoma Cancer Relapsed high grade serous ovarian (fallopian tube, primary peritoneal) carcinoma
Conditions
Interventions
After an initial safety run-in phase, part randomised (to the phase II part of the trial) to one of the three trial treatment arms by a computer which decides randomly which treatment the patient will
Sponsors
NHS Greater Glasgow and Clyde
University of Glasgow
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Age = 16 years 2. Written informed consent prior to participating in the trial and any trial related procedures being performed 3. Histologically confirmed high-grade serous or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer 3.1. If mixed histology, > 50% of the primary tumour must be confirmed to be high-grade serous or endometrioid upon review by local pathology, with 3 - <12 months from last platinum containing regimen. These time points are defined as time between Day 1 last cycle and RECIST evaluable disease progression. 7. RECIST evaluable disease (by RECIST criteria v1.1). Patients with CA125 progression in the absence of RECIST evaluable disease will NOT be eligible. 8. Already known to have a deleterious germline or somatic BRCA1/2 mutation (proof required from local testing) OR be gBRCAwt LoHHIGH or BRCA 1/2 mutant as confirmed by the central laboratory (Foundation Medicine). Note: Tissue from BRCA mutant patients already identified locally will be required for confirmation. Sufficient archival formalin-fixed paraffin-embedded (FFPE) tumour tissue of adequate quality (see below) must be available for the central laboratory testing. Cytospin blocks from ascites are not acceptable. To be acceptable for Foundation Medicine testing, tumour tissue must be the most recently obtained specimen with at least 30% tumour content, and a minimum of 80% nucleated cellular content. If it is a mixed tumour, the majority of the specimen sent for central testing and translational work should be the high-grade component, e.g. not the carcinosarcoma / clear cell features. In the event that archival tumour tissue is not available a screening biopsy sample must be collected and provided to the central laboratory. 9. Willingness to undergo mandatory biopsy pre cycle 1 day 1, where safe and technically feasible. RECIST target lesions should b
Exclusion criteria
Exclusion criteria: 1. Prior chemotherapy, biological therapy, radiation therapy, hormonal anti-cancer therapy, immunotherapy, other anticancer agents within 28 days of starting trial treatment (not including palliative radiotherapy at focal, non-RECIST target sites). Treatment with any investigational agent within the preceding 4 weeks or within 5 half-lives of the investigational agent, whichever is longer. 2. Any prior PARP inhibitor, anti PD-1 or anti PD-L1, anti-PD-L2, anti-CD137, or cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) 3. Pregnant or lactating women 4. Women of childbearing age and reproductive potential who are not willing, or their male partners are not willing, to use two highly effective forms of contraception. In addition, patients will be excluded if they are not willing to use contraception for the duration of the trial and for 6 months following the last dose of trial treatment. 5. With the exception of alopecia and stable peripheral neuropathy from previous taxanes, any unresolved toxicities from prior chemotherapy should be no greater than CTCAE (Version 4.03) Grade 1 at the time of starting trial treatment 6. Major surgery within 3 weeks or minor surgery within 5 days of trial entry (excluding placement of vascular access devices) 7. Spinal cord compression, known leptomeningeal involvement or brain metastases, unless treated and stable either on physiological doses of steroids (eg <10mg prednisolone) or off steroids altogether for at least 4 weeks prior to randomisation 8. Oral anticoagulants such as warfarin are not permitted. Anticoagulation with low molecular weight heparin and anti-Factor X is allowed. Patients who have a new diagnosis of deep vein thrombosis or pulmonary embolism within 2 weeks of randomisation are permitted if clinically stable on a therapeutic dose of LMWH or anti-Factor X. 9. Any haemopoietic growth factors (e.g., G-CSF, GM-CSF) and blood / platelet transfusions within 2 weeks prior to randomization or patients requiring regular blood transfusions (e.g. 2 or more times in the 4 weeks prior to first dose of trial drug), granulocyte colony-stimulating factor, or platelet transfusions 10. Hospitalization for bowel obstruction within 3 months prior to randomization 11. Any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib 12. Has a known diagnosis of immunodeficiency, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (screening for these is not required). Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Includes prior organ transplantation including allogenic stem-cell transplant. The following are exceptions to this exclusion criterion: 12.1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection) 12.2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent 12.3. Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication) 13. Has a known history of active TB (Bacillus Tuberculosis) 14. Previous additional malignancy that is progressing or has required active treatment in the last 2 years. Please discuss with the CTU if further clarification
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) is measured using the RECIST v 1.1. with CT scans performed every 8 weeks for the first year and then every 16 weeks until disease progression. PFS is defined as the time from randomisation to confirmed progression or death form any cause (whichever occurs first). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall response is measured using RECIST 1.1 and separately on combined RECIST / GCIG CA125 criteria using CT scans performed every 8 weeks for the first year and then every 16 weeks until disease progression 2. Duration of response 3. Overall survival measured using date of death. Overall survival is defined as the time from the date of randomisation until death from any cause. 4. Safety and tolerability is assessed using the based on toxicities coded using NCI-CTCAE v4.03.Toxicities are reviewed before treatment, Days 1/15/28/42 for all cycles, and at the end of treatment 5. Quality of life is assessed using the EQ-5D-5L questionnaire at baseline, before each cycle of treatment and at the end of treatment 6. resource use for health economic assessment prior to each cycle of treatment and at the end of treatment | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactKaren;Laura Allan;Alexander
;
Outcome results
None listed