Clinical Trial: Adjuvant HIPEC in High Risk Colon Cancer

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Colon Cancer at High Risk of Peritoneal Carcinomatosis

Brief Summary:

This study aims to determine the oncological effectiveness of adjuvant HIPEC, using intraperitoneal oxaliplatin with concomitant i.v. 5-FU/LV, following a curative resection of a T4 or intra-abdominally perforated Colon cancer in preventing the development of peritoneal carcinomatosis in addition to the standard adjuvant systemic treatment.

Hypothesis:

The hypothesis is that adjuvant HIPEC preceding routine adjuvant systemic therapy using i.p. oxaliplatin with concomitant i.v. 5-FU/LV following a curative resection of a T4 or intra-abdominally perforated colon cancer reduces the development of peritoneal carcinomatosis in comparison to standard adjuvant systemic treatment alone.


Detailed Summary:

Background:

The peritoneum is the second most common site of recurrence in patients with colon cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult and adjuvant systemic treatment does not seem to affect peritoneal dissemination in contrast to haematogenous dissemination in the liver or lungs. Of all patients eventually presenting with clinically apparent PC, only a quarter have potentially curable disease. The curative option is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC), but the effectiveness depends highly on the extent of disease and is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant intraperitoneal therapy in high risk colon cancer patients in order to prevent the development of PC with treatment at a subclinical stage.

Study design:

This will be a multicentre study in which 176 eligible patients will be randomized to adjuvant HIPEC followed by adjuvant systemic chemotherapy in the experimental arm, or the standard adjuvant systemic chemotherapy alone in the control arm. Adjuvant HIPEC will be performed preferably simultaneously or within 10 days after resection of the primary tumour, either by laparoscopy or open approach, similar to the technique used for resection of the primary tumour. If adjuvant HIPEC cannot be performed within 10 days (i.e. complicated postoperative course), the procedure will be delayed until 5 to 8 weeks postoperatively. Subsequently, patients will receive routine adjuvant chemotherapy (CAPOX) within 3 weeks from HIPEC. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Current Primary Outcome: Peritoneal recurrence free survival [ Time Frame: 18 months ]

Peritoneal recurrence-free survival at 18 months determined by CT and if negative by laparoscopy.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Treatment related toxicity of adjuvant HIPEC, including 30-day complication rate, re-intervention rate, and re-admission rate [ Time Frame: 5 years ]
  • Hospital stay for simultaneous and staged HIPEC, either open or laparoscopic [ Time Frame: 10 weeks ]
  • False-negative rate of CT-scan for peritoneal metastases [ Time Frame: 5 years ]
    The presence or absence of peritoneal metastasis on CT-scan will be compared to the findings during diagnostic laparoscopy, histological biopsy or fine needle aspiration cytology.
  • Patterns of dissemination (peritoneal plus or minus distant metastases) [ Time Frame: 5 years ]
  • Disease-free survival [ Time Frame: 5 years ]
  • Overall survival [ Time Frame: 5 years ]
  • Quality of life [ Time Frame: 5 years ]


Original Secondary Outcome:

  • Treatment related toxicity of adjuvant HIPEC, including 30-day complication rate, re-intervention rate, and re-admission rate [ Time Frame: 5 years ]
  • Hospital stay for simultaneous and staged HIPEC, either open or laparoscopic [ Time Frame: 10 weeks ]
  • Peritoneal metastasis on CT-scan [ Time Frame: 5 years ]
    The presence or absence of peritoneal metastasis on CT-scan will be compared to the findings during diagnostic laparoscopy, MRI-imaging or cytology.
  • Patterns of dissemination (peritoneal plus or minus distant metastases) [ Time Frame: 5 years ]
  • Disease-free survival [ Time Frame: 5 years ]
  • Overall survival [ Time Frame: 5 years ]
  • Quality of life [ Time Frame: 5 years ]


Information By: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Dates:
Date Received: August 22, 2014
Date Started: March 2015
Date Completion: April 2022
Last Updated: September 15, 2016
Last Verified: September 2016