Body Surface Area-based vs Concentration-based Dosing of Cisplatin for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Women With Advanced Ovarian Cancer

Phase 2

Active, not recruiting

• Conditions: Fallopian Tube Carcinoma; FIGO Stage III Ovarian Cancer; Peritoneal Cancer
• Interventions: Drug: Cisplatin 100 mg/m2; Drug: Cisplatin 40 mg/l

• Registration Number: NCT05406674
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

Cytoreductive surgery (CRS) with the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) is used in current clinical practice in selected patients with advanced ovarian cancer. Clinical evidence for the benefit of HIPEC in ovarian cancer comes from the pivotal phase 3 OVHIPEC trial. Worldwide, two established strategies exist for dosing of HIPEC protocols, which follow either a body surface area (BSA)-based or a concentration-based approach. Since both strategies result in different exposure to intra-peritoneal chemotherapy, we aim to compare the pharmacokinetics and safety of both strategies.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-31
• Study First Submitted QC: 2022-06-03
• Study First Posted: 2022-06-06
• Study Start: 2022-06-15
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-16
• Last Update Posted: 2025-07-20
• Primary Completion: 2026-12
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

1. signed and written informed consent

2. age ≥ 18 years

3. patients eligible for interval cytoreductive surgery

   1. histological proven FIGO stage III primary high grade serous ovarian, fallopian tube, or extra-ovarian cancer
   2. when only cytology is performed to confirm the diagnosis ovarian carcinoma, immunohistochemistry should be performed including keratin 7, keratin 20, p53, PAX8
   3. neo-adjuvant chemotherapy consists of (at least) 3 courses of carboplatin/paclitaxel
   4. following 2 cycles of chemotherapy no progression should occur

4. treated with optimal or complete interval cytoreductive surgery

5. fit for major surgery, WHO performance status 0-2

6. adequate bone marrow function (hemoglobin level >5.5 mmol/L; leukocytes >3 x 109/L; platelets >100 x 109 /L)

7. adequate hepatic function (ALT, AST and bilirubin <2.5 times upper limit of normal)

8. 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)

9. able to understand the patient information

Exclusion Criteria

1. history of previous malignancy treated with chemotherapy
2. opting for fertility-sparing surgery

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Cisplatin 100 mg/m2	Patients in Arm A are treated with interval cytoreductive surgery (with no more than 1 cm residual disease) and cispaltin-based HIPEC with a dosage of 100 mg/m2
Arm B	Cisplatin 40 mg/l	Patients in Arm B are treated with interval cytoreductive surgery (with no more than 1 cm residual disease) and cisplatin- based HIPEC with a dosage of 40 mg/L perfusate.

Primary Outcome Measures

Name	Time	Method
Intratumoral platinum (Pt) concentration at the end of perfusion after 90 minutes (in ng/mg wet tissue)	End of perfusion after 90 minutes

Secondary Outcome Measures

Name	Time	Method
Toxicity evaluation (CTCAE 5.0)	The occurrence of adverse events will be monitored until 6 weeks after surgery	Grade 3-5 will be reported
Platinum (Pt) concentration in normal tissue (in ng/mg wet tissue)	End of perfusion
Platinum (Pt) concentration in tumor tissue after 30 minutes and 60 minutes of perfusion (in ng/mg wet tissue)	After 30 minutes and 60 minutes of perfusion
Concentration versus time curve and area-under-the-curve (AUC) of intra-peritoneal Platinum (Pt) during perfusion	During perfusion
Maximum Concentration (Cmax) Platinum (Pt) in perfusate during perfusion	During perfusion
Time to Maximum Concentration (Tmax) Platinum (Pt) in perfusate during perfusion	During perfusion
Terminal elimination half-life (t1/2) Platinum (Pt) in perfusate during perfusion	During perfusion
Clearance from perfusate at the end of perfusion	End of perfusion
Overall Survival (OS)	Will be evaluated after 3 and 5 years after the last patient last visit

Trial Locations

Locations (2)

Antoni van Leeuwenhoek (NKI-AVL); 🇳🇱 Amsterdam, Netherlands

UMCU; 🇳🇱 Utrecht, Netherlands