Clinical trial NCT05406674: Body Surface Area-based vs Concentration-based Dosing of Cisplatin for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Women With Advanced Ovarian Cancer
Official title: Body Surface Area-based vs Concentration-based Dosing of Cisplatin for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Women With Advanced Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: FIGO Stage III Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Carcinoma
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
First posted: 2022-06-06
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Intratumoral platinum (Pt) concentration at the end of perfusion after 90 minutes (in ng/mg wet tissue)
timeFrame: End of perfusion after 90 minutes
Secondary outcomes:
measure: Toxicity evaluation (CTCAE 5.0)
timeFrame: The occurrence of adverse events will be monitored until 6 weeks after surgery
measure: Platinum (Pt) concentration in normal tissue (in ng/mg wet tissue)
timeFrame: End of perfusion
measure: Platinum (Pt) concentration in tumor tissue after 30 minutes and 60 minutes of perfusion (in ng/mg wet tissue)
timeFrame: After 30 minutes and 60 minutes of perfusion
measure: Concentration versus time curve and area-under-the-curve (AUC) of intra-peritoneal Platinum (Pt) during perfusion
timeFrame: During perfusion
measure: Maximum Concentration (Cmax) Platinum (Pt) in perfusate during perfusion
timeFrame: During perfusion
measure: Time to Maximum Concentration (Tmax) Platinum (Pt) in perfusate during perfusion
timeFrame: During perfusion
measure: Terminal elimination half-life (t1/2) Platinum (Pt) in perfusate during perfusion
timeFrame: During perfusion
measure: Clearance from perfusate at the end of perfusion
timeFrame: End of perfusion
measure: Overall Survival (OS)
timeFrame: Will be evaluated after 3 and 5 years after the last patient last visit
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek (NKI-AVL)
city: Utrecht
country: Netherlands
facility: UMCU
Study officials:
affiliation: NKI-AvL
name: W. van Driel, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: