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Sponsors and Collaborators: |
Dutch Colorectal Cancer Group Sanofi-Aventis Hoffmann-La Roche |
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Information provided by: | Dutch Colorectal Cancer Group |
ClinicalTrials.gov Identifier: | NCT00394992 |
The primary aim of this study is to investigate whether the addition of the new anti-cancer drug bevacizumab (Avastin) to the combination of the chemotherapeutic agents capecitabine (Xeloda) and oxaliplatin (Eloxatin) reduces (slows down) the recurrence of metastatic disease after a radical resection of liver metastases in patients with colorectal cancer.
Condition | Intervention | Phase |
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Colorectal Cancer Liver Metastases |
Drug: oxaliplatin+capecitabine Drug: xaliplatin+capecitabine+bevacizumab |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study |
Official Title: | Randomized Phase III Study Post Radical Resection of Liver Metastasis of Colorectal Cancer: Bevacizumab in Combination With XELOX as Adjuvant Chemotherapy vs XELOX Alone |
Estimated Enrollment: | 500 |
Study Start Date: | December 2006 |
Estimated Study Completion Date: | December 2013 |
Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1oxaliplatin+capecitabine: Active Comparator
postoperatively oxaliplatin 130 mg/m2 i.v. day 1 plus capecitabine 1000 mg/m2 b.i.d. on day 1-14, q3w
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Drug: oxaliplatin+capecitabine
postoperatively oxaliplatin 130 mg/m2 i.v. day 1 plus capecitabine 1000 mg/m2 b.i.d. on day 1-14, q3w
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2oxaliplatin+capecitabine+bevacizumab: Experimental
postoperatively oxaliplatin 130 mg/m2 i.v. day 1 plus bevacizumab 7.5 mg/kg on day 1 plus capecitabine 1000 mg/m2 b.i.d. on day 1-14, q3w
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Drug: xaliplatin+capecitabine+bevacizumab
postoperatively oxaliplatin 130 mg/m2 i.v. day 1 plus bevacizumab 7.5 mg/kg on day 1 plus capecitabine 1000 mg/m2 b.i.d. on day 1-14, q3w
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The primary therapy of colorectal cancer is surgical resection, but more than half of all colorectal cancer patients eventually die of metastatic disease. Although the introduction of new anticancer agents with efficacy in metastatic colorectal cancer, e.g.: oxaliplatin and irinotecan, and the targeted agents cetuximab and bevacizumab has changed therapeutic nihilism, chemotherapy alone has failed to cure these patients.
It is estimated that 15-20 % of colorectal cancer patients present with synchronous liver metastases and approximately 50% of the patients with colorectal tumors will develop liver metastases at some point during the course of their disease. In almost one third of the cases, the liver was shown at autopsy to be the only site of cancer spread. This is in accordance with the 20% - 45 % five-year survival obtained with surgical resection of hepatic metastases.
Previous studies have not shown a clear benefit of adjuvant chemotherapy after metastatectomy of liver metastases. However, most of these studies have been performed with 5-fluorouracil with or without other older cytostatic drugs. Since new effective agents have been developed (e.g.: capecitabine, oxaliplatin and bevacizumab), adjuvant combination treatment with these agents might be more effective. These drugs have proven activity as first line palliative treatment of recurrent metastases. This raises the question if this new effective treatment is of value as an adjuvant treatment after metastatectomy.
As mentioned before, a two-arm EORTC study: neoadjuvant and adjuvant FOLFOX vs no chemotherapy in resectable liver metastases of colorectal cancer is almost completed (Nordlinger et al). It is expected that this study will show a 10% 3 year DFS benefit in favour of th treatment arm. Definitive data of this trial will be released at the end of 2006, and will most probably lead to adjuvant treatment post metastasectomy as a standard of care. In the HEPATCIA trial we anticipate on this by using adjuvant XELOX as the control arm.
As mentioned earlier, the 3-year disease free survival in patients post metastatectomy of liver metastases is approximately 25%. There is no data available on the effectivity of the XELOX regimen as adjuvant treatment after metastatectomy of colorectal cancer metastases. The EORTC study was designed to demonstrate a 10% improvement in 3y DFS. Assuming that this study is positive, 3 year DFS would be 35% in the control arm (XELOX post liver resection).
Since bevacizumab inhibits angiogenesis, which is required for growth of metastases, this drug may be valuable in the adjuvant setting. Several studies investigate the value of this drug in combination with fluoropyrimidines as an adjuvant regimen after resection of primary colorectal cancers. However, at this moment there is no mature data available of these studies. Therefore, we assume an increase in 3-year disease free survival of 10%, to 45% in the XELOX and bevacizumab treatment arm.
This study will therefore evaluate patients with resectable liver metastasis without extra-hepatic disease, investigating whether the capecitabine, oxaliplatin and bevacizumab regimen is superior to capecitabine and oxaliplatin alone applied as adjuvant treatment, in order to extent disease free and overall survival.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Richard van Hillegersberg, MD PhD | +31 30 2506968 | rsc@rsconsultancy.nl |
Contact: Raymond J. Schmidt, MD | +31 575 441001 | rsc@rsconsultancy.nl |
Netherlands | |
Universitair Medisch Centrum Utrecht | Recruiting |
Utrecht, Netherlands, 3508 GA | |
Contact: Richard van Hillegersberg, MD PhD +31 30 2506968 R.vanHillegersberg@umcutrecht.nl |
Principal Investigator: | Richard van Hillegersberg, MD PhD | Universitair Medisch Centrum Utrecht |
Responsible Party: | DCCG ( R. van Hillegersberg MD PhD ) |
Study ID Numbers: | HEPATICA |
Study First Received: | November 1, 2006 |
Last Updated: | September 5, 2008 |
ClinicalTrials.gov Identifier: | NCT00394992 |
Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Colorectal cancer Liver metastasis Radical resection Adjuvant therapy |
Bevacizumab Capecitabine Oxaliplatin Hepatica |
Capecitabine Liver Diseases Digestive System Neoplasms Gastrointestinal Diseases Colonic Diseases Liver neoplasms Bevacizumab Intestinal Diseases |
Rectal Diseases Intestinal Neoplasms Liver Neoplasms Oxaliplatin Digestive System Diseases Neoplasm Metastasis Gastrointestinal Neoplasms Colorectal Neoplasms |
Antimetabolites Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Growth Substances Physiological Effects of Drugs Angiogenesis Inhibitors Pharmacologic Actions |
Neoplasms Neoplastic Processes Neoplasms by Site Pathologic Processes Therapeutic Uses Growth Inhibitors Angiogenesis Modulating Agents |