Comparing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) Using Mitomycin-C Versus Melphalan for Colorectal Peritoneal Carcinomatosis

ColoRectal Cancer Clinical Trial

Official title: Phase II Single-Blind Randomized Trial Comparing Morbidity of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) Using Mitomycin-C Versus Melphalan for Colorectal Peritoneal Carcinomatosis

Status Recruiting

Clinical Trial Summary

The purpose of this trial is to compare the morbidity and mortality of CRS-HIPEC using mitomycin-C versus melphalan for colorectal peritoneal carcinomatosis. Morbidity and mortality will measured using the Comprehensive Complication Index (CCI) score, Common terminology criteria for adverse events (CTCAE version 4.03), and the Clavien-Dindo Classification.

Clinical Trial Description

BACKGROUND: Peritoneal dissemination of cancer (peritoneal carcinomatosis) from gastrointestinal malignancies, meaning tumor deposits along the inside abdominal or pelvic wall and surfaces of the intestines and organs, has historically been considered a terminal disease. Although peritoneal surface tumors can respond to systemic therapy as a sole form of treatment, patient survival remains poor and cure is considered impossible.

A plasma-peritoneal barrier makes systemic therapy relatively ineffective against peritoneal surface disease. In the 1990's, cytoreductive surgery and hyperthermic intraperitoneal therapy (CRS-HIPEC) began to be popularized as a more effective treatment.

Hyperthermic intraperitoneal chemotherapy has several advantages. High-dose chemotherapy can be used due to the plasma-peritoneal barrier resulting in little absorption into the blood stream. Hyperthermia itself has cytotoxic effects and can increase the depth of tumor penetration by the chemotherapeutic agent up to 3 mm and moreover can potentiate its antineoplastic effects. Although CRS-HIPEC has been considered standard treatment for ruptured appendiceal neoplasms and primary peritoneal mesothelioma, in the past decade its indications have broadened to other peritoneal surface malignant processes.

Historically, morbidity and mortality associated with CRS-HIPEC was considerably higher than other complex operations, and thus its use was often discouraged. However, in recent times, especially in high-volume centers, morbidity and mortality has drastically improved. Due to recent improvements in mortality after major surgical interventions, including HIPEC, the focus has shifted toward other endpoints besides efficacy, such as morbidity, quality of life and cost.

While HIPEC is universally felt to be a vital component after cytoreductive surgery, there is a lack of consensus on the optimal regimen, especially the chemotherapeutic agent that should be used. In the United States, the most commonly used agent during HIPEC is mitomycin-C, however, it remains unknown if mitomycin-C is the optimal drug to use with regards to toxicity and survival.

Randomized prospective studies are needed comparing the toxicity and effectiveness of HIPEC with mitomycin-C to other agents.

OBJECTIVE: To compare morbidity and mortality after CRS-HIPEC utilizing mitomycin-C versus melphalan.

METHODS: In this study, patients will be randomized to one of two treatment arms: Arm 1.) Mitomycin-C initial dose of 15 mg/m2, 45 minutes into the perfusion a maintenance dose of 5 mg/m2 will be administered; or Arm 2): Melphalan 60 mg/m2 45 minutes into the perfusion. Morbidity will be measured during immediate and short-term surgical recovery (up to 90 days post-hospital discharge). Mortality will be measured beginning with the date of surgery and ending with the date of participant death. ;

Related Conditions & MeSH terms

• Appendiceal Neoplasms
• Cancer, Appendiceal
• Carcinoma
• ColoRectal Cancer
• Fever
• Hyperthermia
• Peritoneal Neoplasms

• NCT number: NCT03073694
• Study type: Interventional
• Source: University of Kansas Medical Center
• Contact: Mazin Al-kasspooles, MD
• Phone: 913-588-6568
• Email: mal-kasspooles@kumc.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: July 14, 2017
• Completion date: July 2025