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Open Access Highly Accessed Study protocol

A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) vs CAPOX alone as adjuvant treatment

Nikol Snoeren1, Emile E Voest2*, Andre M Bergman3, Otilia Dalesio4, Henk M Verheul5, Rob AEM Tollenaar6, Joost RM van der Sijp7, Sander B Schouten1, Inne HM Borel Rinkes1 and R van Hillegersberg1

Author Affiliations

1 Department of Surgical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands

2 Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands

3 Department of Medical Oncology, Antonie van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands

4 Department of Biometrics, Antonie van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

5 Department of Medical Oncology, VU Medical Center De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands

6 Department of Surgery, Leiden, Albinusdreef 2, 2333 ZA Leiden, the Netherlands

7 Department of Surgery, Lijnbaan 32, 2512 VA Den Haag, the Netherlands

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BMC Cancer 2010, 10:545  doi:10.1186/1471-2407-10-545

Published: 11 October 2010

Abstract

Background

About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX.

Methods/design

The Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall survival, safety and quality of life.

Conclusion

The HEPATICA study is designed to demonstrate a disease free survival benefit by adding bevacizumab to an adjuvant regime of CAPOX in patients with colorectal liver metastases undergoing a radical resection or resection in combination with RFA.

Trial Registration

ClinicalTrials.gov Identifier NCT00394992