Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neo-adjuvant Therapy and the Effect on Synchronous Metastatic Growth

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.
 
ClinicalTrials.gov Identifier: NCT00659022
Recruitment Status : Unknown
Verified February 2009 by Radboud University.
Recruitment status was:  Recruiting
First Posted : April 16, 2008
Last Update Posted : September 12, 2011
Sponsor:
Information provided by:
Radboud University

Tracking Information
First Submitted Date  ICMJE April 3, 2008
First Posted Date  ICMJE April 16, 2008
Last Update Posted Date September 12, 2011
Study Start Date  ICMJE July 2008
Estimated Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2008)
  • 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 ]
  • Difference in response of liver metastases between control group and experimental groups determined by FDG-PET [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2008)
  • Toxicity of neo-adjuvant treatment [ Time Frame: 12 weeks ]
  • Complications of surgery [ Time Frame: 4 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neo-adjuvant Therapy and the Effect on Synchronous Metastatic Growth
Official Title  ICMJE Accelerated Growth of Synchronous Colorectal Liver Metastases: Effects of Neo-adjuvant Therapy
Brief Summary

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

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Neoplasms
  • Liver Neoplasms
Intervention  ICMJE
  • Procedure: immediate surgery (resection of primary colorectal tumor)
    no neo-adjuvant treatment, immediate surgery
  • Drug: neo-adjuvant treatment with bevacizumab
    neoadjuvant treatment with bevacizumab during 7 weeks prior to surgery of the colorectal primary
    Other Name: Avastin
  • Drug: neoadjuvant treatment with capecitabine and oxaliplatin
    neoadjuvant treatment with CAPOX during 7 weeks prior to surgery of the colorectal primary
    Other Names:
    • Xeloda
    • Eloxatin
  • Drug: neo-adjuvant treatment with bevacizumab, capecitabine and oxaliplatin
    neoadjuvant treatment with bevacizumab and CAPOX during 7 weeks prior to surgery of the colorectal primary
    Other Names:
    • Avastin
    • Xeloda
    • Eloxatin
Study Arms  ICMJE
  • Active Comparator: A
    immediate surgery of the primary colorectal tumor, no neoadjuvant therapy
    Intervention: Procedure: immediate surgery (resection of primary colorectal tumor)
  • Experimental: B
    neoadjuvant treatment with bevacizumab during 7 weeks prior to surgery of the colorectal primary
    Intervention: Drug: neo-adjuvant treatment with bevacizumab
  • Experimental: C
    neoadjuvant treatment with CAPOX during 7 weeks prior to surgery of the colorectal primary
    Intervention: Drug: neoadjuvant treatment with capecitabine and oxaliplatin
  • Experimental: D
    neoadjuvant treatment with bevacizumab and CAPOX during 7 weeks prior to surgery of the colorectal primary
    Intervention: Drug: neo-adjuvant treatment with bevacizumab, capecitabine and oxaliplatin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: April 10, 2008)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2014
Estimated Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with histological proven primary colorectal cancer and synchronous unresectable liver metastases with or without additional extrahepatic disease (primary tumor in situ). Unresectable liver metastases defined as too extensive hepatic involvement or extrahepatic disease.
  • Measurable liver metastases on CT scan (RECIST), positive signal of liver metastases on FDG-PET scan
  • Age: 18-80 years
  • WHO performance scale 0-1
  • ASA category I or II
  • Negative pregnancy test in women with childbearing potential
  • Life expectancy > 12 weeks
  • Laboratory values obtained ≤ 3 weeks prior to study entry, disease evaluation performed ≤ 3 weeks prior to study entry. Adequate bone marrow function (Hb > 6.5 mmol/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L), renal function (serum creatinine < 1.5 x ULN or creatinine clearance ≥ 50 mL/min (calculated according to Cockroft and Gault), liver function (ASAT and ALAT ≤ 3 x upper normal limit, serum bilirubin ≤ 2 x upper normal limit)
  • Written informed consent

Exclusion Criteria:

  • Signs of bowel obstruction or bleeding from primary tumor
  • Prior chemotherapy treatment for advanced disease, prior treatment with anti-angiogenic drugs
  • Resectable liver metastases
  • Diabetes mellitus
  • Continuous use of immunosuppressive agents
  • Pregnancy or lactation
  • Contra-indications for systemic therapy with bevacizumab (Avastin)/ chemotherapy (Xelox)
  • Concurrent severe or uncontrolled disease (i.e. uncontrolled hypertension, congestive heart failure, myocardial infarction < 12 months, chronic active infection)
  • Sensory neuropathy > grade 1
  • Serious non-healing wound or ulcer
  • Patients (M/F) with reproductive potential not implementing adequate contraceptive measures
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to start of bevacizumab
  • Bleeding disorders or coagulopathy or need for full-dose anticoagulation
  • Signs or symptoms of brain metastases
  • Cerebrovascular accident or transient ischemic attack within the past 12 months
  • Impairment of gastrointestinal function or -disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow tablets)
  • Presence of proteinuria at baseline as defined by: patients with > 1 g of protein/24 hr by a 24-hour urine collection.
  • Any concomitant disorder preventing the safe administration of study drugs or surgical procedure.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00659022
Other Study ID Numbers  ICMJE SILENT
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party T.J.M Ruers, PhD, The Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital Amsterdam
Study Sponsor  ICMJE Radboud University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Theo Ruers, PhD The Netherlands Cancer Institute
Principal Investigator: Kees Punt, PhD Radboud University Nijmegen Medical Center
Principal Investigator: Wim Oyen, PhD Radboud University Nijmegen Medical Center
PRS Account Radboud University
Verification Date February 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP