Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Bevacizumab; Oxaliplatin; levo-folinic acid; 5-fluorouracil; Capecitabine
Intervention description: 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.; 85mg/m2 IV every 2 weeks for up to 24 weeks; 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks; 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); 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)
Intervention MeSH terms: Leucovorin; Folic Acid; Bevacizumab; Capecitabine; Fluorouracil; Oxaliplatin; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 230.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: metastatic; stage IV

Summary:

      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.
    

Eligibility 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