Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer (OBELICS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Cancer Institute, Naples
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute, Naples
ClinicalTrials.gov Identifier:
NCT01718873
First received: October 29, 2012
Last updated: February 20, 2014
Last verified: February 2014

October 29, 2012
February 20, 2014
May 2012
September 2014   (final data collection date for primary outcome measure)
number of objective responses [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01718873 on ClinicalTrials.gov Archive Site
  • progression free survival [ Time Frame: one year ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • worst grade toxicity per patient [ Time Frame: evaluated every 2 weeks up to 6 months ] [ Designated as safety issue: Yes ]
  • changes in quality of life [ Time Frame: measured at baseline, 12 weeks, and 24 weeks ] [ Designated as safety issue: No ]
  • progression free survival [ Time Frame: one year ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: 30 months ] [ Designated as safety issue: No ]
  • worst grade toxicity per patient [ Time Frame: evaluated every 2 weeks up to 3 months ] [ Designated as safety issue: Yes ]
  • changes in quality of life [ Time Frame: measured at baseline, 12 weeks, and 24 weeks ] [ Designated as safety issue: No ]
  • evaluation of prognostic and predictive factors [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    circulating endothelial cell counts, cytokines, antiangiogenic factors, single nucleotide polymorphisms of VEGF, leukocyte count 24 hours after administration of bevacizumab, and mRNA will be evaluated in blood samples of participating consenting patients, for correlation with clinical outcomes of patients
  • change in metabolic tumor volume [ Time Frame: 11 days from first day of first cycle of chemotherapy ] [ Designated as safety issue: No ]
    measured by PET scan
  • evaluation of prognostic and predictive factors [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    circulating endothelial cell counts, circulating endothelial cell counts, cytokines, antiangiogenic factors, single nucleotide polymorphisms of VEGF, leukocyte count 24 hours after administration of bevacizumab, and mRNA will be evaluated in blood samples of participating consenting patients, for correlation with clinical outcomes of patients
  • change in metabolic tumor volume [ Time Frame: 15 days from first dose of bevacizumab ] [ Designated as safety issue: No ]
    measured by PET scan
 
Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer
Randomized Phase 3 Study on the Optimization of Bevacizumab With mFOLFOX/mOXXEL in the Treatment of Patients With Metastatic Colorectal Cancer

The purpose of this study is to evaluate if giving bevacizumab prior to chemotherapy compared to giving bevacizumab at the same time as chemotherapy improves patient overall response to treatment.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Colorectal Cancer
  • Drug: Bevacizumab
    5 mg/kg every 2 weeks for up to 24 weeks. After 24 weeks, those patients without disease progression will receive bevacizumab 7.5 mg/kg every 3 weeks until progression of disease or unacceptable toxicity.
    Other Name: Avastin
  • Drug: Oxaliplatin
    85mg/m2 IV every 2 weeks for up to 24 weeks
  • Drug: levo-folinic acid
    200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks
  • Drug: 5-fluorouracil
    400 mg/m2 IV bolus followed by 2400 mg/m2 IV infusion over 46 hours, every 2 weeks for up to 24 weeks (given in mFOLFOX-6 schedule)
  • Drug: Capecitabine
    1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)
  • Experimental: bevacizumab before chemotherapy
    Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
    Interventions:
    • Drug: Bevacizumab
    • Drug: Oxaliplatin
    • Drug: levo-folinic acid
    • Drug: 5-fluorouracil
    • Drug: Capecitabine
  • Active Comparator: bevacizumab with chemotherapy
    Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
    Interventions:
    • Drug: Bevacizumab
    • Drug: Oxaliplatin
    • Drug: levo-folinic acid
    • Drug: 5-fluorouracil
    • Drug: Capecitabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
230
March 2015
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histological diagnosis of colorectal adenoma carcinoma
  • Stage IV disease
  • Presence of at least one measurable target lesion (according to RECIST), and not previously radiated.
  • Age ≥ 18 e ≤ 75 years
  • ECOG Performance status 0-1
  • Life expectancy >3 months
  • Adequate recovery from surgery, with at least 28 days from surgery to date of pre-study biopsy.
  • Adequate contraception for male and female patients of child bearing potential
  • informed consent

Exclusion Criteria:

  • More than one previous line of therapy for metastatic disease
  • Prior treatment with bevacizumab or oxaliplatin (previous treatment with irinotecan,, cetuximab, fluoropyrimidine, folic acid are permitted)
  • Primary tumor that is stenosing and/or that infiltrates the entire thickness of the intestinal wall
  • Regular use of NSAIDs or aspirin
  • Bleeding disorders or coagulopathy
  • Concurrent anticoagulant therapy
  • Suspected or cerebral metastases (to verify in the presence of symptoms)
  • Neutrophils < 2000 / mm3, platelets < 100,000 / mm3, hemoglobin < 9g/dl
  • Creatinine > 1.5 times the upper normal limit
  • GOT and/or GPT > 2.5 times the upper normal limit, bilirubin > 1.5 times the upper normal limit in absence of liver metastases
  • GOT and/or GPT > 5 times the upper normal limit, bilirubin > 3 times the upper normal limit in presence of liver metastases
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ
  • Congestive heart failure, ischemic coronary events within past 12 months, uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension
  • Active or uncontrolled infection
  • Any concomitant condition that, in the investigator's opinion, would contraindicate the use of any of the study drugs
  • Pregnancy or lactation
  • Central nervous system disorders or peripheral neuropathy > grade 1 (CTCAE v. 4.0)
  • Inability to comply with follow up procedures of the study
Both
18 Years to 75 Years
No
Contact: Antonio Avallone, M.D. +39 081 5903629 avalloneantonio@libero.it
Italy
 
NCT01718873
OBELICS, 2011-004997-27
No
National Cancer Institute, Naples
National Cancer Institute, Naples
Not Provided
Principal Investigator: Antonio Avallone, M.D. National Cancer Institute, Naples
National Cancer Institute, Naples
February 2014

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