Ovarian CancerPhase 1/2PROOVNCT07460180
The PROOV Study: Exploiting the Synergistic Effect of PARP Inhibition With Cisplatin and Hyperthermia During Interval Cytoreductive Surgery and HIPEC in Ovarian Cancer
A Phase 1/2 study testing Olaparib in people with Ovarian Cancer and Epithelial Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
The PROOV study is an open-label, monocenter, single-arm, prospective phase I/II trial with a safety lead-in, evaluating the feasibility of combining PARPi with HIPEC in stage III EOC patients. Read more about this study
- Who is it for?
- Ages 18 to 100 years, women only
- Conditions the study is for
- Ovarian Cancer, Epithelial Cancer, Fallopian Tube Cancer
- What is being tested?
- Olaparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 May 2025to 1 May 2032
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
NKI-AvL
Amsterdam, 1066CX
madelief schreuder-goedheijt, 0205129111, m.schreudergoedheijt@nki.nl
leah frenkel, 0205129111, l.frenkel@nki.nl
About this study
The PROOV study is an open-label, monocenter, single-arm, prospective phase I/II trial with a safety lead-in, evaluating the feasibility of combining PARPi with HIPEC in stage III EOC patients. Phase I is a dose-finding phase with a time-to-event Bayesian Optimal Interval (TITE-BOIN) design, in which three doses of olaparib are evaluated to identify the optimal dose for the phase II part and future trials. The recommended phase II dose (RP2D) will be determined based on the experienced DLTs per dose level and the level of intra-tumor and systemic enzymatic PARP inhibition. During Phase II, the safety profile of the RP2D will be assessed in a total cohort of 40 patients. To provide a proof-of-concept, efficacy will be explored in both translational analyses and survival data.
Read the detailed description
Peritoneal recurrence is common in patients with advanced epithelial ovarian cancer (EOC) despite cytoreductive surgery (CRS) and platinum-based chemotherapy. Novel therapeutic strategies have emerged, such as Hyperthermic Intra PEritoneal Chemotherapy (HIPEC) added to interval CRS and maintenance therapy with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors (PARPi). While these treatment strategies effectively delay recurrences, long-term survival for patients with advanced EOC remains poor.
It has been demonstrated that PARP inhibition synergizes with platinum compounds, but concurrent treatment with systemically administered platinum is considered too (myelo-)toxic. On the other hand, hyperthermia induces a transient state of homologous recombination deficiency (HRD) that is required for a therapeutic effect of PARP inhibition. Hence, we hypothesize that administering HIPEC when PARP is inhibited could optimally exploit the synergistic effect of local cisplatin and hyperthermia at the peritoneal surface without adding systemic toxicity.
The study population will consist of min. 40 to max. 55 patients with histologically proven FIGO stage III and operable stage IV high-grade serous ovarian cancer, peritoneal cancer, or fallopian tube carcinoma eligible for interval CRS with HIPEC, meaning that only patients with a response or stable disease after neo-adjuvant chemotherapy (NACT) will be eligible.
The study participants enrolled in the PROOV will receive seven days of PARPi (olaparib, Lynparza®) twice a day. The dosage will be either 100mg, 150mg or 300mg, depending on the phase of the trial. The treatment with olaparib will start 7 days before the scheduled CRS, with the final dose administered in the morning prior to the surgery. Following achievement of optimal or complete interval CRS, HIPEC will be performed by administering cisplatin intraperitoneally (either 100 mg/m2 with a maximum of 220 mg, or 40 mg/L) and sodium thiosulphate intravenously. Blood samples and peritoneal tissue samples (before and after HIPEC) will be collected for the translational analyses. Whenever possible, tissue at recurrence will also be collected.
- Conditions
- Ovarian Cancer, Epithelial Cancer, Fallopian Tube Cancer
- Being tested
- Olaparib
- Keywords
- safety, efficacy, PARP inhibitor, HIPEC, Hyperthermic intraperitoneal Chemotherapy
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
seven days of PARPi (olaparib, Lynparza®) twice a day. The dosage will be either 100mg, 150mg or 300mg, depending on the phase of the trial.
| Study group | Role | What they receive |
|---|---|---|
| PARPi (olaparib, Lynparza®) | Experimental | Not described Receives: Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and toxicity of combining PARP-inhibitors with HIPEC
Safety lead in phase 1 part: evaluation of dose limiting toxicities by CTCAE v.5 and Clavien dindo from start PARP inhibition until 28 days postoperatively. Evaluated dosages are 100mg, 150mg and 300mg BID of olaparib.
Further toxicity will be evaluated in phase 2, in which an additional number of patients will be treated with recommended phase 2 dose.
Measured: 4 years
Secondary outcomes (1)
The degree of PARP (enzymatic) inhibition
Blood and intracellular PARP activity will be measured, and the extent of PARP inhibition will be quantified as percentage reduction (%) from baseline activity levels in all enrolled patients.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start1 May 2025
- Primary completion1 May 2027 (estimated)
- Study completion1 May 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07460180
- Sponsor's protocol ID
- M23PRV
- Acronym
- PROOV
- Status last verified
- Mar 2026
- First submitted
- 27 Nov 2025
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The PROOV Study: Exploiting the Synergistic Effect of PARP Inhibition With Cisplatin and Hyperthermia During Interval Cytoreductive Surgery and HIPEC in Ovarian Cancer
- ClinicalTrials.gov ID
- NCT07460180
- Acronym / sponsor ID
- PROOV / M23PRV
- Conditions
- Ovarian Cancer, Epithelial Cancer, Fallopian Tube Cancer
- Keywords
- safety, efficacy, PARP inhibitor, HIPEC, Hyperthermic intraperitoneal Chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- 1 May 2025 (actual)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 1 May 2032 (estimated)
- First posted
- 10 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The PROOV study is an open-label, monocenter, single-arm, prospective phase I/II trial with a safety lead-in, evaluating the feasibility of combining PARPi with HIPEC in stage III EOC patients. Phase I is a dose-finding phase with a time-to-event Bayesian Optimal Interval (TITE-BOIN) design, in which three doses of olaparib are evaluated to identify the optimal dose for the phase II part and future trials. The recommended phase II dose (RP2D) will be determined based on the experienced DLTs per dose level and the level of intra-tumor and systemic enzymatic PARP inhibition. During Phase II, the safety profile of the RP2D will be assessed in a total cohort of 40 patients. To provide a proof-of-concept, efficacy will be explored in both translational analyses and survival data.
Detailed description
Peritoneal recurrence is common in patients with advanced epithelial ovarian cancer (EOC) despite cytoreductive surgery (CRS) and platinum-based chemotherapy. Novel therapeutic strategies have emerged, such as Hyperthermic Intra PEritoneal Chemotherapy (HIPEC) added to interval CRS and maintenance therapy with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors (PARPi). While these treatment strategies effectively delay recurrences, long-term survival for patients with advanced EOC remains poor.
It has been demonstrated that PARP inhibition synergizes with platinum compounds, but concurrent treatment with systemically administered platinum is considered too (myelo-)toxic. On the other hand, hyperthermia induces a transient state of homologous recombination deficiency (HRD) that is required for a therapeutic effect of PARP inhibition. Hence, we hypothesize that administering HIPEC when PARP is inhibited could optimally exploit the synergistic effect of local cisplatin and hyperthermia at the peritoneal surface without adding systemic toxicity.
The study population will consist of min. 40 to max. 55 patients with histologically proven FIGO stage III and operable stage IV high-grade serous ovarian cancer, peritoneal cancer, or fallopian tube carcinoma eligible for interval CRS with HIPEC, meaning that only patients with a response or stable disease after neo-adjuvant chemotherapy (NACT) will be eligible.
The study participants enrolled in the PROOV will receive seven days of PARPi (olaparib, Lynparza®) twice a day. The dosage will be either 100mg, 150mg or 300mg, depending on the phase of the trial. The treatment with olaparib will start 7 days before the scheduled CRS, with the final dose administered in the morning prior to the surgery. Following achievement of optimal or complete interval CRS, HIPEC will be performed by administering cisplatin intraperitoneally (either 100 mg/m2 with a maximum of 220 mg, or 40 mg/L) and sodium thiosulphate intravenously. Blood samples and peritoneal tissue samples (before and after HIPEC) will be collected for the translational analyses. Whenever possible, tissue at recurrence will also be collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PARPi (olaparib, Lynparza®) | Experimental | Drug: Olaparib |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
Key exclusion criteria (4 listed)
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olaparibseven days of PARPi (olaparib, Lynparza®) twice a day. The dosage will be either 100mg, 150mg or 300mg, depending on the phase of the trial. | Drug | PARPi (olaparib, Lynparza®) |
Primary outcome
Safety and toxicity of combining PARP-inhibitors with HIPEC
Time frame: 4 years
Safety lead in phase 1 part: evaluation of dose limiting toxicities by CTCAE v.5 and Clavien dindo from start PARP inhibition until 28 days postoperatively. Evaluated dosages are 100mg, 150mg and 300mg BID of olaparib. Further toxicity will be evaluated in phase 2, in which an additional number of patients will be treated with recommended phase 2 dose.
1 secondary outcome
The degree of PARP (enzymatic) inhibition
Time frame: 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
Related trials for Ovarian Cancer
Active, not recruiting
Culturally-Informed Counseling in Latinas at High Risk for Hereditary Breast or Ovarian Cancer
No Evidence of Disease, BRCA1 Syndrome
Active, not recruitingPhase 1
Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer
FIGO Stage IVA Ovarian Cancer, FIGO Stage IVB Ovarian Cancer
Active, not recruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers
Pancreatic Cancer, Renal Cell Cancer
Active, not recruitingPhase 2/3
Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Fallopian Tube High Grade Serous Adenocarcinoma, Ovarian High Grade Serous Adenocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Olaparib in people with Ovarian Cancer and Epithelial Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact madelief schreuder-goedheijt (0205129111, m.schreudergoedheijt@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and toxicity of combining PARP-inhibitors with HIPEC (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026; AzTrials last refreshed its copy on 26 Oct 2026.