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

Sponsor
Yonsei University
Study ID
NCT01632722
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
20 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Bevacizumab, mFOLFOX, FOLFIRI — DRUG
    ArmA (postoperative arm) Postoperative mFOLFOX or FOLFIRI regimen, every 2weeks for 12cycles Bevacizumab 5mg/kg IV, every 2weeks for 11cycles beginning with cycle 2
  • Bevacizumab, mFOLFOX, FOLFIRI — DRUG
    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)

Study Details

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.

Key Dates

First listed
Jul 3, 2012
Start date
Jun 30, 2012
Status verified
Jun 2018
Primary completion
May 31, 2018
Completion
Jun 30, 2018

Study Design

Enrollment
79 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: ArmA
  • Active Comparator: ArmB

Primary Outcome Measure

2 years recurrence-free survival (2Y-RFS) [ Time Frame: 2 years ]

Related Studies