Fallopian Tube Carcinoma, FIGO Stage III Ovarian Cancer, Peritoneal Cancer
Conditions
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.
Interventions
Cisplatin 100 mg/m2 milligram(s)/square meter
DRUGCisplatin 40 mg/l
Cisplatin 40 mg/I milligram(s)/litre
Sponsors
The Netherlands Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Toxicity evaluation (CTCAE 5.0) | The occurrence of adverse events will be monitored until 6 weeks after surgery | Grade 3-5 will be reported |
| 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 | — |
| Time to Maximum Concentration (Tmax) Platinum (Pt) in perfusate during perfusion | During perfusion | — |
Countries
Netherlands
Outcome results
None listed