Acronym

COLOPEC

Name of the study

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC Dutch randomized multicentre trial.

Researchers and contact information

Lead investigator:

Dr. P.J. (Pieter) Tanis
E: p.j.tanis@amc.uva.nl

Other principal investigators

Prof. dr. C.J.A. (Kees) Punt
E: c.punt@amc.uva.nl

Dr. V. (Vic) Verwaal
E: vic.verwaal@clin.au.dk

Prof. dr. W.A. (Willem) Bemelman
E: w.a.bemelman@amc.uva.nl

Trial statistician

Dr. M.G.W. (Marcel) Dijkgraaf
E: m.g.dijkgraaf@amc.uva.nl

Coordinating investigators

Drs. C.E.L. (Lotje) Klaver
E: c.e.klaver@amc.uva.nl

D.D. (Daan) Wisselink, PhD candidate
E: d.d.wisselink@amc.uva.nl

Tel: +316 22350655

Summary study

Rationale: The peritoneum is the second most common site of recurrence of colorectal cancer. Early detection of peritoneal carcinomatosis (PC) is difficult and when the disease becomes clinically overt, prognosis is poor. This underlines the need for adjuvant therapy to minimize the risk of outgrowth of peritoneal micro metastases. Possibly, adjuvant HIPEC is effective.

Primary objective: To determine the effectiveness of adjuvant HIPEC in preventing the development of PC in high-risk patients.

Study design: In February 2015, accrual of 176 patients with T4 or perforated colon cancer will begin. After curative resection of the primary tumor, patients will be randomized to adjuvant HIPEC (oxaliplatin, 30 minutes) followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm.

Primary endpoint:Primary endpoint is peritoneal disease free survival at 18 months.

Secondary endpoints: Secondary endpoints are treatment-related toxicity of adjuvant HIPEC, including 30-day complication rate, re-intervention rate, and re-admission rate; hospital stay for simultaneous and staged HIPEC, either open or laparoscopic; 3 and 5-year disease-free survival and overall survival; quality of life (EORTC-30, EORTC-CR29) and costs (general, per year free of PC, per quality adjusted life year) (EQ-5D-5 L, iMTA MCQ and iMTA PCQ, adapted to the current study setting and target population).

Sample size: Adjuvant HIPEC is expected to reduce the 25% risk of peritoneal recurrence to 10%. Approximately 25 % of CRC patients with a pT4 or perforated primary tumour is expected to develop PC. Adjuvant HIPEC is expected to result in a 60 % relative risk reduction in peritoneal recurrence based on the currently available literature (see below). To detect an absolute 15 % difference in PC recurrence-free survival at 18 months (90 % peritoneal recurrence-free under HIPEC plus systemic chemotherapy against 75 % peritoneal recurrence free under systemic chemotherapy), a total number of 176 patients (88 in each arm) is needed (Kaplan-Meier, one-sided, alpha = 0.05, power of 80 %, drop-out 5 %).

As of now, June 2017, 204 patients have been included and randomized in both arms of the COLOPEC trial, which has been closed for inclusion.

 

 

Intervention

Control arm
Adjuvant systemic chemotherapy following primary resection

Experimental arm
HIPEC + adjuvant systemic chemotherapy following primary resection

Participating centers

• Academisch Medisch Centrum, Amsterdam
• Antoni van Leeuwenhoek Ziekenhuis, Amsterdam
• Catharina Ziekenhuis, Eindhoven
• Erasmus Medisch Centrum, Rotterdam
• Radboud Universitair Medisch Centrum, Nijmegen
• St. Antonius Ziekenhuis, Nieuwegein
• Universitair Medisch Centrum Groningen, Groningen
• VU Medisch Centrum, Amsterdam