Cytoreduction Followed by Normothermic Versus Hyperthermic Intraperitoneal Intraoperative Chemoperfusion (HIPEC): a Study in Peritoneal Carcinomatosis

Study Overview
=================
Brief Summary
-----------------
Peritoneal carcinomatosis from appendix or colon (large bowel) cancer is treated in suitable patients with surgery followed by instillation of heated chemotherapy inside the abdominal cavity. This procedure is termed 'Hyperthermic intraoperative Peritoneal Chemoperfusion' or HIPEC. Many center perform HIPEC with high dose oxaliplatin, a standard chemotherapy drug active against colon cancer, administered during 30 minutes at 41°C. The hypothesis of this study is, that chemoperfusion at normal (37.5°C) temperature but longer duration (90 minutes) may be safer and at least as efficient. Patients will be treated with one of three possible HIPEC regimens using oxaliplatin: high dose, 30 min, 41°C; high dose, 30 min, 37.5°C; or low dose, 90 min, 37.5°C. The outcome parameters are pharmacokinetic and pharmacodynamic: using specialized techniques, tissue penetration of chemotherapy and cancer cell kill effects will be compared in order to establish the safest and most active HIPEC regimen.

Official Title
-----------------
Phase II Study Comparing Normothermic Versus Hyperthermic Intraoperative Chemoperfusion With Oxaliplatin in Patients With Peritoneal Metastases From Appendiceal or Colon Cancer

Conditions
-----------------
Peritoneal Carcinomatosis

Intervention / Treatment
-----------------
* Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion
* Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion
* Drug: Hyperthermic intraoperative Peritoneal Chemoperfusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with peritoneal carcinomatosis from colorectal origin (including appendiceal mucinous neoplasms and the pseudomyxoma syndromes) amenable for cytoreduction and HIPEC. Exclusion Criteria: No written informed consent Irresectable and/or metastatic disease found during surgery Known allergy to oxaliplatin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxaliplatin 37°C, high dose, 30 minutes<br> | Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion<br>* Dose: 460 mg/m², duration: 30 minutes, temperature 37°C<br>|
| Placebo Comparator: Oxaliplatin 41 °C, high dose, 30 minutes<br> | Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion<br>* Dose: 460 mg/m², duration: 30 minutes, temperature 41°C<br>|
| Active Comparator: Oxaliplatin 37°C, low dose, 90 minutes<br> | Drug: Hyperthermic intraoperative Peritoneal Chemoperfusion<br>* Dose: 200 mg/m², duration: 90 minutes, temperature 37°C<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | Scoring of postoperative morbidity according to the Dindo-Clavien system | Until discharge or within 30 days | 
| Mortality | The number of deaths will be recorded. | Until discharge or within 30 days | 
| Area under the perfusate concentration versus time curve (AUC) of platinum | Measurements of platinum in perfusate samples on the high dose interventions. | Before addition of chemotherapy, at 10, 20 and 30 minutes after addition of chemotherapy | 
| Area under the perfusate concentration versus time curve (AUC) of platinum | Measurements of platinum in perfusate samples on the low dose intervention. | Before addition of chemotherapy, at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after addition of chemotherapy | 
| Area under the plasma concentration versus time curve (AUC) of platinum | Measurements of platinum in perfusate samples on the high dose interventions. | Before addition of chemotherapy, at 10, 20, 30,45, 60, 90 minutes and 2, 4, 8, 12, 18, 24 hours after addition of chemotherapy | 
| Area under the plasma concentration versus time curve (AUC) of platinum | Measurements of platinum in plasma samples on the low dose intervention. | Before addition of chemotherapy, at 10, 20, 30, 40, 50, 60, 70, 80, 90 minutes and 2, 4, 8, 12, 18, 24 hours after addition of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue Concentration (Cmax) of Platinum | Platinum concentration will be measured after removal of perfusate. | after 30 or 90 minutes | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peritoneal carcinomatosis from colorectal or appendiceal origin