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

This study is currently recruiting participants.
Verified November 2012 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: November 26, 2012
Last verified: November 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
 Drug: Bevacizumab
Drug: Oxaliplatin
Drug: levo-folinic acid
Drug: 5-fluorouracil
Drug: Capecitabine
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase 3 Study on the Optimization of Bevacizumab With mFOLFOX/mOXXEL in the Treatment of Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:
  • number of objective responses [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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


Estimated Enrollment: 230
Study Start Date: May 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bevacizumab before chemotherapy
Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
 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)
Active Comparator: bevacizumab with chemotherapy
Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)
 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)

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01718873

Contacts
Contact: Antonio Avallone, M.D. +39 081 5903629 avalloneantonio@libero.it

Locations
Italy
Istituto Nazionale Tumori Fondazione G. Pascale Recruiting
Napoli, Italy
Sponsors and Collaborators
National Cancer Institute, Naples
Investigators
Principal Investigator: Antonio Avallone, M.D. National Cancer Institute, Naples
  More Information

No publications provided

Responsible Party: National Cancer Institute, Naples
ClinicalTrials.gov Identifier: NCT01718873     History of Changes
Other Study ID Numbers: OBELICS, 2011-004997-27
Study First Received: October 29, 2012
Last Updated: November 26, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by National Cancer Institute, Naples:
metastatic
stage IV

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Capecitabine
Oxaliplatin
Bevacizumab
 Leucovorin
Folic Acid
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on May 21, 2013