Combining olaparib with cisplatin HIPEC during interval cytoreductive surgery for ovarian cancer
The PROOV Study: Exploiting the Synergistic Effect of PARP Inhibition With Cisplatin and Hyperthermia During Interval Cytoreductive Surgery and HIPEC in Ovarian Cancer
This study will test whether giving the PARP inhibitor olaparib around interval cytoreductive surgery with heated intraperitoneal cisplatin (HIPEC) is safe and feasible for adults with advanced high‑grade serous ovarian or fallopian tube cancer who responded to neoadjuvant chemotherapy.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 55 (estimated) |
| Ages | 18 Years to 100 Years |
| Sex | Female |
| Sponsor | The Netherlands Cancer Institute Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Amsterdam) |
| Trial ID | NCT07460180 on ClinicalTrials.gov |
What this trial studies
This is an open‑label, single‑center, single‑arm phase I/II trial with a safety lead‑in that combines perioperative olaparib with cisplatin HIPEC during interval cytoreductive surgery. Phase I uses a time‑to‑event Bayesian Optimal Interval (TITE‑BOIN) dose‑finding design testing three olaparib dose levels to identify a recommended phase II dose based on dose‑limiting toxicities and measurements of intra‑tumor and systemic PARP inhibition. Phase II will enroll about 40 patients to characterize the safety profile of the recommended dose and explore proof‑of‑concept efficacy through translational biomarkers and survival outcomes. The intervention aims to exploit hyperthermia‑induced homologous recombination deficiency to enhance local synergy between PARP inhibition and cisplatin without adding systemic platinum toxicity.
Who should consider this trial
Good fit: Ideal candidates are adults (≥18) with histologically confirmed high‑grade serous ovarian, fallopian tube, or extra‑ovarian carcinoma with FIGO stage III or selected resectable stage IV disease who have responded or have stable disease after neoadjuvant chemotherapy and are planned for interval cytoreductive surgery with HIPEC.
Not a fit: Patients with progressive or unresectable disease after neoadjuvant chemotherapy, those unfit for major surgery or HIPEC, or those with prior intolerance to PARP inhibitors or non‑eligible histologies are unlikely to benefit.
Why it matters
Potential benefit: If successful, the approach could increase tumor killing at the peritoneal surface while avoiding added systemic toxicity, potentially delaying recurrence and improving survival.
How similar studies have performed: Both HIPEC added to interval CRS and PARP inhibitor maintenance have supporting clinical data in ovarian cancer, but combining perioperative PARP inhibition with HIPEC is a novel approach that has not yet been tested in larger trials.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* In order to be eligible to participate in this study, a subject must meet all of the following criteria:
* Signed and written informed consent
* At least 18 years of age and able to understand patients' information
* FIGO stage III primary high-grade serous ovarian, fallopian tube, or extra-ovarian cancer.
* FIGO stage IV is allowed in the following situations:
* Resectable stage IV desease, such as local bowel involvement, iatrogenic abdominal wall metastases or umbilical lesions
* Stage IV based on cardiophrenic lymph nodes \<1cm
* The diagnosis should be confirmed with either histology or cytology. If the diagnosis of ovarian carcinoma is based on cytology only, immunohistochemistry, including keratin 7, keratin 20, p53, PAX8 should be considered for confirmation of the diagnosis (at the discretion of the pathologist)
* Eligible and planned for interval cytoreductive surgery with HIPEC
* Neo-adjuvant chemotherapy consists of at least 3 courses of carboplatin/paclitaxel
* Patients should have response or stable disease after NACT; no progression should occur
* Operability has been evaluated in a multidisciplinary team (MDT) meeting via CT scan, MRI or diagnostic laparoscopy and an optimal or complete interval CRS is deemed feasible
* Fit for major surgery, WHO performance status 0-2
* Adequate bone marrow function (hemoglobin level \>5.5 mmol/L, leukocytes \>3 x10\^9/L, platelets \> 100 x10\^9/L)
* Adequate hepatic function (ALT, AST, and bilirubin \< 2.5 times the upper limit of normal)
* Adequate renal function (creatinine clearance ≥ 60 ml/min using Cockcroft-Gault formula or 24-hour measurement or ml/min/1,73 m2 using MDRD or CKD-EPI)
Exclusion Criteria:
* A potential subject who meets any of the following criteria will be excluded from participation in this study:
* History of previous malignancy treated with chemotherapy
* Opting for fertility-sparing surgery
* Concurrent use of potent inducers or inhibitors of CYP3A4 as assessed with the KNMP "G-standaard" that cannot be stopped temporarily
Where this trial is running
Amsterdam
- NKI-AvL — Amsterdam, Netherlands (Recruiting)
Study contacts
- Study coordinator: madelief schreuder-goedheijt
- Email: m.schreudergoedheijt@nki.nl
- Phone: 0205129111
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.