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

This study is currently recruiting participants.
Verified July 2012 by Yonsei University
Sponsor:
Information provided by (Responsible Party):
Yonsei University
ClinicalTrials.gov Identifier:
NCT01632722
First received: June 28, 2012
Last updated: July 2, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Colorectal Cancer
Liver Metastasis
Drug: Bevacizumab, mFOLFOX, FOLFIRI
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • 2 years recurrence-free survival (2Y-RFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 218
Study Start Date: June 2012
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)


  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01632722

Contacts
Contact: Joong Bae Ahn, M.D., Ph.D. vvswm513@yuhs.ac

Locations
Korea, Republic of
Severance Hospital Recruiting
Seoul, Korea, Republic of
Contact: Joong Bae Ahn, M.D., Ph.D.       vvswm513@yuhs.ac   
Severance Hospital Recruiting
Seoul, Korea, Republic of
Contact: Joong Bae Ahn       vvswm513@yuhs.ac   
Sponsors and Collaborators
Yonsei University
  More Information

No publications provided

Responsible Party: Yonsei University
ClinicalTrials.gov Identifier: NCT01632722     History of Changes
Other Study ID Numbers: 4-2012-0166
Study First Received: June 28, 2012
Last Updated: July 2, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Yonsei University:
colorectal cancer, liver metastasis, bevacizumab, perioperative chemotherapy,postoperative chemotherapy

Additional relevant MeSH terms:
Colorectal Neoplasms
Liver Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Liver Diseases
Neoplastic Processes
Pathologic Processes
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014