A Phase II randomised trial comparing immune priming by low dose oral cyclophosphamide plus olaparib versus priming by olaparib alone, prior to combination therapy with olaparib plus durvalumab, versus single agent olaparib alone, in asymptomatic platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancers with homologous recombination repair defects (SOLACE2).

The University of Sydney0 sites114 target enrollmentApril 27, 2018

ConditionsOvarian cancer Fallopian tube cancer Peritoneal cancer Cancer - Ovarian and primary peritoneal

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Ovarian cancer
Sponsor: The University of Sydney
Enrollment: 114
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

April 27, 2018

End Date

July 31, 2024

Last Updated

last year

Study Type

Interventional

Sex

Female

Investigators

Sponsor

The University of Sydney

Eligibility Criteria

Inclusion Criteria

•1\. Women, aged 18 years and older, with histologically confirmed high\-grade serous carcinoma of the ovary, fallopian tube or primary peritoneum.
•2\. Undergone prior adequate debulking surgery, as appropriate, and 1 line of platinum\-based chemotherapy. Patients who received bevacizumab or hormonal therapy as part of first\-line treatment are eligible.
•3\. Known germline BRCA1 and BRCA2 status. Both BRCA mutant and BRCA wild\-type patients are eligible, but they must have normalisation of CA125 to less than upper limit of normal (ULN), defined as 35 units/mL, by the end of first\-line chemotherapy.
•4\. CA125 progression after first\-line treatment, occurring 6 months or more following the last dose of chemotherapy. Participants must have raised CA125 readings twice the ULN (greater than or equal to 70 kU/L) on 2 occasions at least 1 week apart. The following circumstances are also considered eligible:
•If CA125 is less than 70 kU/L, patient must have evaluable disease on imaging (RECIST measurable or non\-measurable);
•In the absence of RECIST measurable disease, CA125 progression (greater than or equal to 70 kU/L) after first\-line treatment occurring 4 months or more following last dose of chemotherapy is allowed.
•5\. No indication for immediate chemotherapy or secondary debulking surgery.
•6\. ECOG performance status of 0\-1\.
•7\. Confirmation of the availability of tumour tissue (FFPE) for translational studies (a cell pellet from ascites or pleural fluid is not acceptable). If no tissue is available, patients will not be eligible for this study.
•8\. Adequate bone marrow function (measured within 28 days prior to registration and with values within the ranges specified below):

Exclusion Criteria

•1\. Previous randomisation in the present study.
•2\. Any previous treatment with a PARP inhibitor, including olaparib.
•3\. Any previous treatment with durvalumab, or any other anti\-PD\-1, anti\-PD\-L1, anti\-PD\-L2, anti\-CTLA\-4 antibodies or any other antibody or drug specifically targeting T cell co\-stimulation or immune checkpoint pathways.
•4\. Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
•5\. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks from the last study dose for other agents.).
•6\. Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
•7\. Patients receiving any systemic anti\-cancer treatment (including endocrine therapy, chemotherapy or VEGF\-targeted agents) or radiotherapy (except for palliative reasons), within 14 days from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used).
•8\. Patients who are unable to swallow orally administered medication or have gastrointestinal disorders likely to interfere with absorption of the study medication (e.g. including but not limited to partial bowel obstruction or chronic malabsorption syndrome, Crohn’s disease and ulcerative colitis).
•9\. Suspected brain or leptomeningeal metastases, untreated brain metastases or current clinical or radiological progression of known brain metastases, or requirement for steroid therapy for brain metastases. Patients with treated brain metastases are eligible if they have been stable and off steroids for equal to or greater than 3 weeks.
•10\. Patients with known haemorrhagic cystitis.