Adjuvant HIPEC in High Risk Colon Cancer
Condition: Colorectal Neoplasms; Peritoneal Neoplasms
MeSH terms: Neoplasms; Colorectal Neoplasms; Peritoneal Neoplasms
Intervention: Adjuvant HIPEC (open/laparoscopic); Standard adjuvant systemic chemotherapy; Diagnostic laparoscopy
Intervention description: Adjuvant HIPEC procedure: access to the abdominal cavity by laparoscopy or laparotomy under general anaesthesia, adhesiolysis if necessary, complete staging of the intra-abdominal cavity, positioning of in- and outflow catheters, perfusion with a minimum of 2l isotonic dialysis fluid at a flow rate of 1-2l/min and an inflow temperature of 42-43˚C. Before the beginning of HIPEC, 5-fluorouracil 400 mg/m2 and leucovorin 20 mg/m2 will be administered intravenously to potentiate oxaliplatin activity. Oxaliplatin (460 mg/m2) is added to the perfusate after attaining at least 42 degrees inflow temperature with a total of 30 minutes perfusion time.; Colon cancer patients with a high risk of developing PC, but do not have (yet) proven macroscopic peritoneal metastasis, are standardly treated with adjuvant systemic chemotherapy. Standard adjuvant systemic chemotherapy consists in the Netherlands of a capecitabine and oxaliplatin (CAPOX) or 5-FU and oxaliplatin (FOLFOX) for a total of 6 months.; Presence or absence of peritoneal recurrence will be evaluated by laparoscopy in case of negative routine examination (CEA and CT thorax/abdomen) at 18 months postoperatively in both study arms.
Intervention MeSH terms: Leucovorin; Capecitabine; Fluorouracil; Oxaliplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 204.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Chemotherapy, Adjuvant; Laparoscopy; Peritoneal Lavage; HIPEC

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  age between 18 and 75 years

          -  Intention to start routine adjuvant systemic therapy

          -  adequate clinical condition to undergo simultaneous HIPEC or re- laparoscopy or
             re-laparotomy with HIPEC within either 10 days or between week 5-8 from --primary
             resection

          -  written informed consent

          -  white blood cell count of at least 3000/mm3, platelet count of at least 100.000/mm3

          -  no bleeding diathesis or coagulopathy

          -  normal creatinine or creatinine clearance of at least 50 ml/min

        Exclusion Criteria:

          -  postoperative complications that interfere with adjuvant HIPEC within 8 weeks (i.e.
             persisting intra-abdominal abscess, significant fascial dehiscence, enteric fistula)

          -  no intention to start routine adjuvant systemic therapy

          -  liver and/or lung metastases

          -  pregnant or lactating women

          -  unstable or uncompensated respiratory or cardiac disease

          -  serious active infections

          -  other concurrent chemotherapy

          -  hypersensitivity to fluorouracil, folinic acid or another substance of leucovorin or
             oxaliplatin

          -  stomatitis, ulceration in the mouth or gastrointestinal tract.

          -  severe diarrhea

          -  severe hepatic and / or renal dysfunction.

          -  plasma bilirubin concentrations greater than 85 μmol/l.

          -  pernicious anemia or other anaemias due to vitamin B12 deficiency.

          -  peripheral sensory neuropathy with functional impairment.