A Study of Bevacizumab and Modified FOLFOX-6 (mFOLFOX-6) in Participants With Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: 5-Fluorouracil (5-FU); Bevacizumab; Levofolinic acid; Oxaliplatin
Intervention description: Participants will receive 5-FU 400 mg per meter-squared (mg/m^2) IV dose on Day 1 of each 2 weeks' cycle followed by 2400 mg/m^2, continuous infusion over 46 hours up to 12 cycles.; Participants will receive 5 mg/kg bevacizumab IV dose on Day 1 of each 2 weeks' cycle up to Cycle 5 and thereafter cycles 7 to 12; followed by maintenance therapy of 5 mg/kg IV every 2 weeks up to 52 weeks (26 cycles).; Participants will receive levofolinic acid 200 mg/m^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle up to 12 cycles.; Participants will receive oxaliplatin 85 mg/m^2 IV infusion over 2 hours on Day 1 of each 2 weeks' cycle up to 12 cycles.
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Oxaliplatin; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The multicenter, open-label, single-arm, non-randomized, two-stage Simon's design, phase II
      study (The CLMO-001 Trial) will evaluate the efficacy and safety of bevacizumab in
      combination with mFOLFOX-6 (Levofolinic acid, 5-Fluorouracil [5-FU] and oxaliplatin) in
      participants with colorectal cancer and liver metastases. Participants will receive
      combination therapy of bevacizumab 5 milligrams per kilogram (mg/kg) intravenous (IV) dose
      and mFOLFOX-6 every 2 weeks during Cycles 1-5 and Cycles 7-12. Participants will receive
      mFOLFOX-6 alone (without bevacizumab) on Cycle 6. In between Cycle 6 and 7, participants will
      undergo liver surgery if operable. Thereafter participants will receive bevacizumab (5 mg/kg
      IV every 2 weeks) alone for 52 weeks (26 cycles) after the end of the post-operative phase
      (maintenance therapy). At the end of the preoperative treatment phase (Cycles 1-6),
      participants showing different alternative conditions admitted by the protocol will undergo
      different management (alternative study designs 1 to 3).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants (male or female), greater than (>) 18 years of age

          -  Histologically confirmed adenocarcinoma of the colon or the rectum

          -  Primitive lesion is at a distance >12 centimeter (cm) from the anal margin for
             participants with primitive rectal tumor

          -  Measurable metastatic disease confined to the liver

          -  Eastern cooperative oncology group (ECOG) performance status 0-1

          -  No previous chemotherapy for metastatic disease or treatment with drugs targeting
             vascular endothelial growth factor receptor (VEGF) or epidermal growth factor receptor
             (EGFR)

          -  Adequate bone marrow, liver and renal function

          -  Urine analysis with proteinuria less than (<) 2+

          -  Use of at least one approved contraceptive method by participants with reproductive
             potential

          -  Written informed consent from the participants

          -  Surgical criteria for hepatic resection

          -  Adjuvant treatment (either only surgery on primitive tumor or surgery on primitive
             tumor + adjuvant chemotherapy) must have been concluded greater than or equal to (>/=)
             6 months before enrollment

        Exclusion Criteria:

          -  Presence of extrahepatic metastases

          -  Evidence of lumbo-aortic and celiac lymph nodes involvement

          -  Radiotherapy within 4 weeks before study start

          -  History of inflammatory bowel disease and/or acute/sub-acute bowel occlusion

          -  Presence of serious non-healing wound or ulcer

          -  Evidence of bleeding diathesis or coagulopathy

          -  Clinically significant cardiovascular disease

          -  Uncontrolled hypertension

          -  Current or recent ongoing treatment with anticoagulants

          -  Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications
             known to predispose to gastrointestinal ulceration

          -  Treatment with any investigational drug within 30 days prior to enrollment

          -  Known allergy to Chinese hamster ovary cell proteins, or any of the components of the
             study medications

          -  Co-existing malignancies diagnosed within the last 5 years with the exception of basal
             cell carcinoma or cervical cancer in situ

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study treatment start, or anticipation of the need for major surgical
             procedure during the course of the study. Interval between endoscopic biopsy or
             colorectal stenting and bevacizumab administration should be evaluated by
             oncologist/endoscopist

          -  Pregnant or lactating women

          -  Any other disease or condition that contraindicates the use of an investigational drug
             or puts the patient at high risk for treatment-related complication

          -  Participants with known Human immunodeficiency virus (HIV) infection

          -  Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection with concomitant
             cirrhosis or undergoing active treatment for the same

          -  Participants who are unable or unwilling to comply with the requirements of the
             protocol and follow-up procedures