Clinical Pharmacology of Platinum-based Hyperthermic Intraperitoneal Chemotherapy (GUTOX)

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

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.

Study Overview

• Status: Completed
• Conditions: Peritoneal Carcinomatosis
• Intervention / Treatment: Other: HIPEC with flushing afterwards; Other: HIPEC without flushing afterwards

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with peritoneal carcinomatosis who undergo HIPEC treatment with oxaliplatin as part of routine care.

Description

Inclusion Criteria:

1. 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.

2. Age ≥ 18 years
3. 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HIPEC patients; Patients with a diagnosis of peritoneal carcinomatosis who undergo HIPEC treatment with oxaliplatin.	Other: HIPEC with flushing afterwards; flushing with saline fluid after HIPEC; Other: HIPEC without flushing afterwards; NO flushing with saline fluid after HIPEC

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Publications and helpful links

General Publications

• de Jong LAW, Elekonawo FMK, Lambert M, de Gooyer JM, Verheul HMW, Burger DM, de Wilt JHW, Chatelut E, Ter Heine R, de Reuver PR, Bremers AJA, van Erp NP. Wide variation in tissue, systemic, and drain fluid exposure after oxaliplatin-based HIPEC: results of the GUTOX study. Cancer Chemother Pharmacol. 2020 Jul;86(1):141-150. doi: 10.1007/s00280-020-04107-y. Epub 2020 Jun 27. Erratum In: Cancer Chemother Pharmacol. 2022 Aug;90(2):189-190.

Helpful Links

• paper

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): June 8, 2019
• Study Completion (Actual): December 30, 2019

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 7, 2017

Study Record Updates

• Last Update Posted (Actual): October 20, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: oxaliplatin; HIPEC; peritoneal carcinomatosis; flushing
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Digestive System Neoplasms; Abdominal Neoplasms; Carcinoma; Peritoneal Neoplasms
• Other Study ID Numbers: GUTOX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No