PArp Inhibitor Resistance Study
High-grade ovarian cancer
Cohort A and B: Imaging-guided (ultrasound or CT), intra-operative or other suitable biopsies will be taken for research purposes from women who have a tumour progressing on PARPi, meet the eligibility criteria and who give written, informed consent. Cohorts A, B and C: Blood will be taken to examine circulating markers of PARPi resistance. 1. Serially (3-4 monthly) for cohort A 2. At progression for cohort B 3. At recruitment for cohort C if the patient is surviving Archival tissue will be accessed. Associated clinical data will be recorded.
Current inclusion criteria as of 07/04/2025: All patients: 1. Age ≥16 years 2. Histological diagnosis of high-grade serous, high-grade endometrioid or carcinosarcoma of the ovary, primary peritoneum or fallopian tube 3. Availability of formalin-fixed, paraffin-embedded tissue taken at the time of original diagnosis of high-grade serous ovarian cancer. This may be primary surgical debulking specimen OR core biopsy. For those with only a core biopsy from time of diagnosis, availability of specimen taken at interval debulking surgery is also requested. 4. Prior treatment with a PARP inhibitor or about to commence maintenance PARPi therapy (cohort A). PARPi can be single agent or in combination with bevacizumab. If PARPi is in combination with a different agent as part of a clinical trial, the patient may still be eligible but this should be confirmed with the Cancer Research UK Glasgow Clinical Trials Unit prior to patient registration. Cohort A: 1. Patients need to be progression-free (defined by no evidence of GCIG Ca125 progression or radiological progression) 2. No contraindication to biopsy 3. Ability to provide written informed consent prior to participating in the study and any study-related procedures being performed 4. Willingness to comply with trial procedures 5. Life expectancy >3 months 6. About to commence, currently receiving PARPi as maintenance therapy or completed PARPi maintenance with no intervening treatment before study entry. Cohort B: 1. Patients need to have radiologically defined progressive disease on PARPi 2. Patients must have disease deemed suitable for imaging-guided biopsy (ultrasound or CT) by an experienced radiologist or suitable for intra-operative biopsy during secondary debulking surgery as determined by an experienced gynaecological oncology surgeon. Other biopsies, such as skin deposits, are also acceptable. However, this must be confirmed with the Cancer Research UK Glasgow Clinical Trials Unit prior to patient registration
Current exclusion criteria as of 07/04/2025: 1. Ovarian, primary peritoneal or fallopian tube cancer of low-grade serous, grades 1 or 2 endometrioid, clear cell or mucinous subtypes 2. Borderline/low malignant potential tumours 3. Any non-epithelial ovarian malignancy 4. Original diagnosis of high-grade serous cancer made on cytology only 5. Discontinued PARPi for toxicity within 3 months of starting PARPi. (exclusion applies to cohorts B & C only). Patients who are recruited to cohort A at initiation of PARPi and subsequently discontinue within 3 months for toxicity will be replaced. Cohort A patients who progress and discontinue PARPi within 3 months will be included in the analysis and will not be replaced 6. Any other severe concurrent disease which may increase the risk associated with trial participation 7. Any psychological, familial, sociological or geographical considerations potentially hampering compliance with the trial and follow-up schedule Previous exclusion criteria: 1. Ovarian, primary peritoneal or fallopian tube cancer of low-grade serous, grades 1 or 2 endometrioid, clear cell or mucinous subtypes 2. Borderline/low malignant potential tumours 3. Any non-epithelial ovarian malignancy 4. Original diagnosis of high-grade serous cancer made on cytology only 5. Discontinued PARPi for toxicity within 3 months of starting PARPi 6. Any other severe concurrent disease which may increase the risk associated with trial participation 7. Any psychological, familial, sociological or geographical considerations potentially hampering compliance with the trial and follow-up schedule