A study to characterise mechanisms of resistance to PARP inhibitors by analysing samples from women with ovarian cancer
- Conditions
- CancerMalignant neoplasm of ovaryHigh-grade ovarian cancer
- Registration Number
- ISRCTN59698923
- Lead Sponsor
- HS Greater Glasgow and Clyde
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Female
- Target Recruitment
- 260
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
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)
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).
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
Study & Design
- Study Type
- Observational
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method umber of PARPi resistant tumours (collected at progression) and matched pre-PARPi tumour samples (collected at baseline) obtained during the recruitment period
- Secondary Outcome Measures
Name Time Method