Neo-adjuvant Therapy and the Effect on Synchronous Metastatic Growth

Sponsor
Radboud University Medical Center
Study ID
NCT00659022
Phase
PHASE2
Status
Unknown

Conditions

Eligibility Criteria

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

Interventions

  • immediate surgery (resection of primary colorectal tumor) — PROCEDURE
    no neo-adjuvant treatment, immediate surgery
  • neo-adjuvant treatment with bevacizumab — DRUG
    neoadjuvant treatment with bevacizumab during 7 weeks prior to surgery of the colorectal primary
  • neoadjuvant treatment with capecitabine and oxaliplatin — DRUG
    neoadjuvant treatment with CAPOX during 7 weeks prior to surgery of the colorectal primary
  • neo-adjuvant treatment with bevacizumab, capecitabine and oxaliplatin — DRUG
    neoadjuvant treatment with bevacizumab and CAPOX during 7 weeks prior to surgery of the colorectal primary

Study Details

Study Hypothesis • As well as in animal models as in patients with colorectal cancer resection of the primary tumor resulted in increase in vascular density, metabolism and secondary tumor growth of the distant metastases. These data strongly suggest an inhibitory effect of the primary tumor on the outgrowth of its metastases. In this study we investigate whether pre-operative treatment with the anti-angiogenic agent bevacizumab and/or chemotherapy before resection of the primary colorectal tumor shifts the balance between angiogenic and anti-angiogenic factors in favor of the anti-angiogenic factors and results in reduced growth of the liver metastases. Eligibility * Histological proven colorectal cancer without signs of bowel obstruction or bleeding * Synchronous liver metastases * WHO performance status 0-1 Treatment * Arm A: immediate surgery of the primary colorectal tumor, no neoadjuvant therapy * Arm B: neoadjuvant treatment with bevacizumab during 7 weeks prior to surgery of the colorectal primary * Arm C: neoadjuvant treatment with CAPOX during 7 weeks prior to surgery of the colorectal primary * Arm D: neoadjuvant treatment with bevacizumab and CAPOX during 7 weeks prior to surgery of the colorectal primary Primary endpoint Difference in response of liver metastases to resection of the primary tumor between the experimental groups and the control group, as determined by histopathological scoring of vascular density, apoptotic and mitotic index and by measurement of the metabolic activity of liver metastases by FDG-PET and SUV measurements. Secondary endpoints Toxicity of neo-adjuvant treatment Complications of surgery

Key Dates

First listed
Apr 16, 2008
Start date
Jul 31, 2008
Status verified
Feb 2009
Primary completion
Mar 31, 2014
Completion
Apr 30, 2014

Study Design

Enrollment
60 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: A
    immediate surgery of the primary colorectal tumor, no neoadjuvant therapy
  • Experimental: B
    neoadjuvant treatment with bevacizumab during 7 weeks prior to surgery of the colorectal primary
  • Experimental: C
    neoadjuvant treatment with CAPOX during 7 weeks prior to surgery of the colorectal primary
  • Experimental: D
    neoadjuvant treatment with bevacizumab and CAPOX during 7 weeks prior to surgery of the colorectal primary

Primary Outcome Measure

Difference in response of liver metastases between control group and experimental groups determined by histopathological scoring of vascular density,apoptotic and mitotic index [ Time Frame: 12 weeks ]

Central Contacts

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