title: A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: the AIO KRK 0110 trial/ML22011 trial.
abstract: BACKGROUND
  Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.
  
  
  METHODS
  The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m(2) bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m(2) BID for 14d (d1-14), irinotecan 200 mg/m(2) (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.
  
  
  CONCLUSIONS
  The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier NCT01249638 EudraCT-No.: 2009-013099-38.
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern, University of Munich, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Giessen
authors.forename: Ludwig Fischer
authors.initials: LF
authors.lastname: von Weikersthal
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.forename: Frank
authors.initials: F
authors.lastname: Kullmann
authors.forename: Ursula
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.forename: Markus
authors.initials: M
authors.lastname: Bangerter
authors.forename: Claudio
authors.initials: C
authors.lastname: Denzlinger
authors.forename: Markus
authors.initials: M
authors.lastname: Sieber
authors.forename: Christian
authors.initials: C
authors.lastname: Teschendorf
authors.forename: Jens
authors.initials: J
authors.lastname: Freiberg-Richter
authors.forename: Christoph
authors.initials: C
authors.lastname: Schulz
authors.forename: Dominik Paul
authors.initials: DP
authors.lastname: Modest
authors.forename: Nicolas
authors.initials: N
authors.lastname: Moosmann
authors.forename: Philipp
authors.initials: P
authors.lastname: Aubele
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009362:Neoplasm Metastasis; D011788:Quality of Life
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin