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

Study Overview
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Brief Summary
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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.

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

Conditions
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FIGO Stage III Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Carcinoma

Intervention / Treatment
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* Drug: Cisplatin 100 mg/m2
* Drug: Cisplatin 40 mg/l


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed and written informed consent age ≥ 18 years patients eligible for interval cytoreductive surgery histological proven FIGO stage III primary high grade serous ovarian, fallopian tube, or extra-ovarian cancer when only cytology is performed to confirm the diagnosis ovarian carcinoma, immunohistochemistry should be performed including keratin 7, keratin 20, p53, PAX8 neo-adjuvant chemotherapy consists of (at least) 3 courses of carboplatin/paclitaxel following 2 cycles of chemotherapy no progression should occur treated with optimal or complete interval cytoreductive surgery fit for major surgery, WHO performance status 0-2 adequate bone marrow function (hemoglobin level >5.5 mmol/L; leukocytes >3 x 109/L; platelets >100 x 109 /L) adequate hepatic function (ALT, AST and bilirubin <2.5 times 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) able to understand the patient information Exclusion Criteria: history of previous malignancy treated with chemotherapy opting for fertility-sparing surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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. 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>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 | Drug: Cisplatin 100 mg/m2<br>* Cisplatin 100 mg/m2 milligram(s)/square meter<br>* Other names: PL 20075/0123;|
| Experimental: Arm B<br>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. | Drug: Cisplatin 40 mg/l<br>* Cisplatin 40 mg/I milligram(s)/litre<br>* Other names: PL 20075/0123;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity evaluation (CTCAE 5.0) | Grade 3-5 will be reported | The occurrence of adverse events will be monitored until 6 weeks after surgery | 
| 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 |