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Open Access Highly Accessed Study protocol

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

Clemens Giessen1, Ludwig Fischer von Weikersthal2, Axel Hinke3, Sebastian Stintzing1, Frank Kullmann4, Ursula Vehling-Kaiser5, Julia Mayerle6, Markus Bangerter7, Claudio Denzlinger8, Markus Sieber9, Christian Teschendorf10, Jens Freiberg-Richter11, Christoph Schulz1, Dominik Paul Modest1, Nicolas Moosmann1, Philipp Aubele1 and Volker Heinemann1*

Author Affiliations

1 Department of Medical Oncology, Klinikum Grosshadern, University of Munich, Germany

2 MVZ Gesundheitszentrum St. Marien, Amberg, Germany

3 WISP GmbH, Langenfeld, Germany

4 Department of Internal Medicine I, Klinikum Weiden, Germany

5 Oncological Practice, Landshut, Germany

6 Department of Medicine, University Hospital Greifswald, Germany

7 Oncological Practice Augsburg, Germany

8 Department of Medicine III, Marienhospital, Stuttgart, Germany

9 Department of Medicine II, Gummersbach Hospital, Gummersbach, Germany

10 St.-Josefs-Hospital Dormund-Hörde, Germany

11 Oncological Practice, Dresden, Germany

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BMC Cancer 2011, 11:367  doi:10.1186/1471-2407-11-367

Published: 23 August 2011

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/Design

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/m2 bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m2 BID for 14d (d1-14), irinotecan 200 mg/m2 (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.

Conclusion

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.

Trial Registration

ClinicalTrials.gov Identifier NCT01249638

EudraCT-No.: 2009-013099-38