A Translational Study of Bevacizumab in Participants With Metastatic Colorectal Cancer
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Oxaliplatin; Capecitabine; Bevacizumab; Leucovorin; 5-Fluouracil; Irinotecan
Intervention description: Participants will receive oxaliplatin 85 milligrams per square meter (mg/m^2) IV infusion on Day 1 of every 2 weeks cycle during alternative Phase A treatment or 130 mg/m^2 on Day 1 of every 3 weeks cycle during Phase A treatment.; Participants will receive capecitabine 1000 mg/m^2 per oral (PO) twice daily on Days 1-14 of 3 weeks cycle during Phase A treatment.; Participants will receive 7.5 mg/kg IV infusion on Day 1 every 3 weeks (Phase A treatment) or 5 mg/kg IV on Day 1 every 2 weeks (Alternative Phase A treatment and Phase B).; Participants will receive leucovorin 400 mg/m^2 IV on Day 1 every 2 weeks (Alternative Phase A treatment and Phase B). Investigators may elect to chose low dose of leucovorin (either 20 mg/m^2 or 50 mg total dose).; Participants will receive 5-fluouracil loading dose of 400 mg/m^2 IV on Day 1 followed by 2400 mg/m^2 continuous IV infusion over 46 hours Day 1 (Alternative Phase A treatment and Phase B).; Participants will receive irinotecan 180 mg/m^2 IV on Day 1 every 2 weeks during Phase B treatment.
Intervention MeSH terms: Leucovorin; Bevacizumab; Capecitabine; Oxaliplatin; Irinotecan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 128.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This open-label, prospective, single-arm, multicenter study will evaluate the relationship of
      the markers of inflammation and progression-free survival (PFS) in participants with
      previously untreated metastatic colorectal cancer. The study consists of two phases: Phase A
      treatment: oral capecitabine plus infusional oxaliplatin (XELOX) plus bevacizumab, or
      modified infusional 5-fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (mFOLFOX6) plus
      bevacizmab administered until first disease progression. Participants will then continue with
      Phase B treatment: infusional 5-FU, LV and irinotecan (FOLFIRI) plus bevacizumab until second
      disease progression. The anticipated time on study treatment is 4 years.
    

Eligibility criteria:

        Inclusion Criteria:

        For resected primary tumor participants, and participants with primary tumor in situ:

          -  Previously untreated metastatic colorectal cancer and not a candidate for curative
             resection

          -  World Health Organization (WHO) performance status of 0-1

          -  Life expectancy of greater than or equal to (>/=) 3 months

          -  Eligible for XELOX, mFOLFOX6, FOLFIRI and bevacizumab treatment in accordance with
             local standards of care and pharmaceutical benefits scheme guidelines

        Additional inclusion criteria for participants with primary tumor in situ:

          -  Intact primary tumor of the colon or the rectum not requiring surgical intervention
             prior to study start

          -  Minimal or asymptomatic primary tumor

        Exclusion Criteria:

        Resected primary tumor participants, and participants with primary tumor in situ:

          -  Previous chemotherapy for metastatic colorectal cancer

          -  Previous neoadjuvant or adjuvant chemotherapy less than 6 months prior to study start

          -  Radiotherapy within 28 days prior to enrollment or not recovered from a radiotherapy

          -  History of non-colorectal cancer (participants are eligible if disease-free for >/=5
             years and the risk of recurrence is deemed low)

          -  Presence of active inflammatory bowel disease

          -  History of gastrointestinal perforations

          -  Peritoneal disease

          -  History of significant bleeding event

          -  Significant vascular disease

          -  Peripheral arterial thrombosis or other thrombotic event within 6 months before study
             start

        Additional exclusion criteria for participants with primary tumor in situ:

          -  Prior endoscopic management of the current tumor

          -  Acute diverticulitis

          -  Presence of intra-abdominal abscess

          -  Active gastroduodenal ulcer