Clinical Pharmacology of Platinum-based Hyperthermic Intraperitoneal Chemotherapy

Study Overview
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Brief Summary
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Currently, there is a lack of knowledge on the effect of additional flushing after HIPEC on tumour platinum exposure, systemic platinum exposure and platinum concentration in drain exudate and thereby personal exposure. Therefore the investigators want to perform a study to investigate the effect of flushing after HIPEC on tumour exposure, systemic exposure and on wound exudate concentration.

Detailed Description
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Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is standard care in the treatment of patients with peritoneal carcinomatosis as a result of intra-abdominal cancers. In many (inter)national centres oxaliplatin is used for the primary HIPEC treatment. Although the oxaliplatin dose of 460mg/m2 is widely accepted, the exact procedure of HIPEC differs between institutions and surgeons. Due to a great variety in the volume of the abdominal cavity, platinum concentration in the perfusate might differ between patients. Moreover, there is no consensus about the usefulness of flushing the HIPEC system with crystalloids at the end of oxaliplatin administration. Flushing is predominantly performed with the idea to minimize both systemic exposure of ultrafilterable platinum and personnel exposure to platinum contaminated exudate. On the other hand, HIPEC without flushing might increase effectiveness because intraperitoneal tumour cells are exposed to high concentrations of oxaliplatin for a longer time period. The option of flushing is based on an individual preference of the surgeon. Currently, there is a lack of knowledge on the effect of flushing on tumour platinum exposure, systemic platinum exposure and platinum concentration in drain exudate and thereby personal exposure. Therefore the investigators want to perform a study to investigate the effect of flushing after HIPEC on tumour exposure, systemic exposure and on wound exudate concentration.

Official Title
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Clinical pharmacoloGy of platinUm-based hyperThermic Intraperitoneal Chemotherapy: Exploration of the Impact of Flushing on tumOur, Systemic and Personnel eXposure (GUTOX)

Conditions
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Peritoneal Carcinomatosis

Intervention / Treatment
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* Other: HIPEC with flushing afterwards
* Other: HIPEC without flushing afterwards


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up. Note: Informed consent may be obtained prior to start of the specified screening window. Note: Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes. Age ≥ 18 years Confirmed diagnosis of preoperatively identifi ed primary or recurrent peritoneal carcinomatosis (PC) of colorectal origin who are planned for HIPEC treatment with oxaliplatin according to routine clinical care Exclusion Criteria: 1) Patients who do not achieve a cytoreduction score of CC-0 will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIPEC patients<br>Patients with a diagnosis of peritoneal carcinomatosis who undergo HIPEC treatment with oxaliplatin. | Other: HIPEC with flushing afterwards<br>* flushing with saline fluid after HIPEC<br>Other: HIPEC without flushing afterwards<br>* NO flushing with saline fluid after HIPEC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in tissue platinum exposure before and after flushing | Change in tissue platinum exposure of non-tumour peritoneal tissue sample before and after flushing with saline | immediately after the oxaliplatin instillate solution is withdrawn from the abdominal cavity and immediately after additional flushing is performed. This takes all place within 1 hour after the start of HIPEC. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| wound exudate platinum concentration | platinum concentration in wound exudate samples will be measured in the drains | until day 3 post-HIPEC | 
| systemic exposure of total and unbound platinum | systemic exposure of total and unbound platinum will be measured using 13 blood samples | until day 3 post-HIPEC | 
| total and unbound platinum concentration in instillate | total and unbound platinum concentration in instillate will be measured in 3 samples of instillate solution that will be obtained during the HIPEC procedure | all samples will be taken within 30 minutes during the HIPEC procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIPEC, oxaliplatin, flushing, peritoneal carcinomatosis