High-grade ovarian cancer Cancer Malignant neoplasm of ovary
Conditions
Interventions
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 eligibilit
Sponsors
NHS Greater Glasgow and Clyde
Eligibility
Sex/Gender
Female
Age
16 Years to 100 Years
Inclusion criteria
Inclusion criteria: 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 (for cohort B). 3. No contraindication to biopsy 4. No systemic anti-cancer treatment (SACT) commenced post PARPi (patients continuing PARPi after surgical resection of a progressing lesion can be included). Patients who have received 1-2 cycles of SACT whilst awaiting surgery may still be eligible for the study, please contact CTU to discuss prior to registration. 5. Ability to provide written informed consent prior to participating in the study and any study-related procedures being performed 6. Willingness to comply with trial procedures 7. Life expectancy >3 months Cohort C: 1. Patients need to have had a lesion which radiologically progressed on PARPi 2. Archival tumour of a lesion progressing post PARPi must be available 3. Ability to provide written informed consent prior to participating in the study and any study-related procedures being performed. Patients with available archival pre and post-PARPi tumour samples, who are no longer living may be identified by their clinical team and registered for the study if samples were collected under generic research consent (or equivalent). Previous inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of PARPi resistant tumours (collected at progression) and matched pre-PARPi tumour samples (collected at baseline) obtained during the recruitment period | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.1. Homologous recombination repair (HRR) gene aberration status using whole exome sequencing (WES) and RNAseq in pre-PARPi tumour samples collected at baseline. 1.2. Homologous recombination (HR) status in pre-PARPi tumour samples collected at baseline, assessed by sequencing of homologous recombinational repair genes 1.3. Status of methylation of HRR genes, assessed by EPIC array in pre-PARPi tumour samples collected at baseline 1.4. HRR gene aberration status in post-PARPi tumour sample collected at progression using WES and RNAseq (where relevant) 1.5. HR status in post-PARPi tumour samples collected at progression for cases previously found to have HRD disease, assessed by sequencing of homologous recombinational repair genes 1.6. Methylation status, assessed by EPIC array in post-PARPi tumour samples collected at progression for cases previously found to have a methylation event in their pre-PARPi tumour. 1.7. Status of other pathways implicated in PARPi resistance as determined by proteomic and other analysis in pre and post-PARPi tumour samples, collected at baseline and progression respectively. 1.8. Proportion of tumours with each resistance mechanism, determined by statistical analysis at the end of the study 2. Proportion of patients where resistance mechanism can be identified in ctDNA, determined by statistical analysis at the end of the study 3. Proportion of patients where resistance mechanism can be identified in ctDNA prior to detection of disease progression by standard clinical assessments (treatment visits), determined by statistical analysis at the end of the study | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed