title: A randomized multicentre phase II trial comparing adjuvant therapy in patients with interferon alpha-2b and 5-FU alone or in combination with either external radiation treatment and cisplatin (CapRI) or radiation alone regarding event-free survival - CapRI-2.
abstract: BACKGROUND
  The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II trial evaluating a combination of adjuvant chemotherapy, immunotherapy and external beam radiation (CapRI-scheme). Two other groups confirmed in phase II trials these results to a certain extent. However, these groups reported severe gastrointestinal toxicity (up to 93% grade 3 or 4 toxicity). In a randomized controlled phase III trial, called CapRI, 110 patients were enrolled from 2004 to 2007 in Germany and Italy to check for reproducibility. Interestingly, much less gastrointestinal toxicity was observed. However, dose-reduction due to haematological side effects had to be performed in nearly all patients. First clinical results are expected for the end of 2009.
  
  
  METHODS
  CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel arms. A de-escalation of the CapRI-scheme will be tested in two different modifications. Patients in study arm A will be treated as outpatients with the complete CapRI-scheme consisting of cisplatin, Interferon alpha-2b and external beam radiation and three cycles of 5-fluorouracil continuous infusion. In study arm B the first de-escalation will be realised by omitting cisplatin. Next, patients in study arm C will additionally not receive external beam radiation. A total of 135 patients with pathologically confirmed R0 or R1 resected pancreatic adenocarcinoma are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival. An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death.
  
  
  CONCLUSIONS
  The aim of this clinical trial is to evaluate de-escalation of the CapRI-scheme. It is hypothesised that removal of cisplatin and radiotherapy will have no significant effect or only a minor impact on the clinical response but result in substantially lower toxicity.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN79802092.
authors.affiliation: Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg 69120, Germany. angela.maerten@med.uni-heidelberg.de
authors.forename: Angela
authors.initials: A
authors.lastname: Märten
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ose
authors.forename: Sabine
authors.initials: S
authors.lastname: Harig
authors.forename: Ulrich
authors.initials: U
authors.lastname: Abel
authors.forename: Marc W
authors.initials: MW
authors.lastname: Münter
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.forename: Guido
authors.initials: G
authors.lastname: Adler
authors.forename: Thomas
authors.initials: T
authors.lastname: Seufferlein
authors.forename: Thomas
authors.initials: T
authors.lastname: Gress
authors.forename: Roland
authors.initials: R
authors.lastname: Schmid
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011446:Prospective Studies; D011994:Recombinant Proteins; D055815:Young Adult
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002945:Cisplatin; D005472:Fluorouracil