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Perioperative vs Postoperative Chemotherapy + Bevacizumab in Colorectal Cancer, Liver Mets

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01632722
Recruitment Status : Completed
First Posted : July 3, 2012
Last Update Posted : June 27, 2018
Information provided by (Responsible Party):
Joong Bae Ahn, Yonsei University

Brief Summary:

Early-stage colorectal cancer(CRC)is localized and resectable, but 20% of the patients have metastatic disease at the time of diagnosis and 50% of all patients eventually die of the disease. The most frequent site of colorectal metastases is the liver, which accounts for 30% to 60% of cases. In these patients, the extent of liver disease is the main determinant of survival. Hepatectomy is the only potentially curative therapy for colorectal liver metastases (CLM), but when traditional criteria for resectability were used, only 10% of patients were candidates for surgical resection.

Although adjuvant systemic therapy after resection of primary colorectal tumors is well established, there are relatively few data on the use of postoperative therapy vs. surgery alone in patients who have undergone resection of liver metastases. In this trial, the absolute increase in the 3-year PFS rate with the addition of FOLFOX4 was a modest but significant 9% in patients who had resection (from 33% to 42%; P = .025). For improving survival in patients with CLM, several studies with biologic agents have been tried. The use of bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has resulted in increased response rates in patients with stage IV colorectal cancer and improved OS and PFS. In an ongoing phase II trial presented in ASCO 2008, in patients who were potentially curable through resection of liver metastases, perioperative treatment with capecitabine and oxaliplatin (XELOX) plus bevacizumab yielded an overall response rate of 73% with stable disease in 21% and a mean PFS of 27 months. Response to chemotherapy significantly correlated with a prolonged PFS (P < .001).

On the basis of these backgrounds, we designed a phase II study to compare the effectiveness of combination chemotherapy with perioperative or postoperative bevacizumab treatment in patients with CLM.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Liver Metastasis Drug: Bevacizumab, mFOLFOX, FOLFIRI Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Perioperative Chemotherapy Plus Bevacizumab Versus Postoperative Chemotherapy Plus Bevacizumab in Patients With Upfront Resectable Hepatic Colorectal Metastases (APPROACH)
Study Start Date : June 2012
Actual Primary Completion Date : May 2018
Actual Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Active Comparator: ArmA Drug: Bevacizumab, mFOLFOX, FOLFIRI

ArmA (postoperative arm)

Postoperative mFOLFOX or FOLFIRI regimen, every 2weeks for 12cycles Bevacizumab 5mg/kg IV, every 2weeks for 11cycles beginning with cycle 2

Active Comparator: ArmB Drug: Bevacizumab, mFOLFOX, FOLFIRI

ArmB (perioperative arm)

Perioperative CTx mFOLFOX or FOFIRI regimen, every 2 weeks for 6 cycles Bevacizumab 5mg/kg IV, every 2 weeks for 5cycles (cycles 1-5)

Postoperative CTx mFOLFOX or FOLFIRI regimen, every 2weeks for 6 cycles Bevacizumab 5mg/kg IV, every 2weeks for 5cycles(cycles 8-12)

Primary Outcome Measures :
  1. 2 years recurrence-free survival (2Y-RFS) [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically proven colorectal adenocarcinoma
  • With hepatic metastasis and no evidence of extrahepatic metastasis (the liver metastases must be determined by a hepatic surgeon to be resectable)
  • 20~80 years
  • ECOG performance status 0 - 1
  • Adequate laboratory findings

Exclusion Criteria:

  • Prior chemotherapy for metastatic disease
  • Prior adjuvant chemotherapy, if administered within 6 months before study entry
  • Previous hepatic-directed therapy including hepatic resection and/or ablation, hepatic arterial infusion therapy, or hepatic radiation therapy
  • Uncontrolled medical illnesses including medically uncontrolled infection, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months
  • Chronic active hepatitis or cirrhosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01632722

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Korea, Republic of
Severance Hospital
Seoul, Korea, Republic of
Sponsors and Collaborators
Yonsei University

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Responsible Party: Joong Bae Ahn, professor, Yonsei University Identifier: NCT01632722    
Other Study ID Numbers: 4-2012-0166
First Posted: July 3, 2012    Key Record Dates
Last Update Posted: June 27, 2018
Last Verified: June 2018
Keywords provided by Joong Bae Ahn, Yonsei University:
colorectal cancer, liver metastasis, bevacizumab, perioperative/postoperative chemotherapy
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors