A Study Comparing the Efficacy and Safety of Vanucizumab and FOLFOX With Bevacizumab and FOLFOX in Participants With Untreated Metastatic Colorectal Cancer (McCAVE)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed mCRC not amenable to potentially curative resection with at least one measurable metastatic lesion, as defined by RECIST v1.1
- Eastern Cooperative Oncology Group (World Health Organization) performance status of 0 or 1
- Adequate hematologic, liver, coagulation, renal, and cardiovascular function
- Recovery from all reversible AEs of previous medical therapies to baseline or National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 1, except for alopecia (any grade)
- Negative serum pregnancy test within 7 days prior to starting study treatment in premenopausal women and women less than (< 2) years after the onset of menopause
Exclusion Criteria:
- Any prior systemic therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, immunotherapy, hormonal therapy) before Day 1 of Cycle 1 for treatment of mCRC
- Malignancies other than CRC within 5 years prior to randomization, except for those with a minimal risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ treated surgically with curative intent
- Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to Day 1 of Cycle 1, except palliative radiotherapy to bone lesions within 7 days prior to Day 1 of Cycle 1
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle
- Pregnant or lactating women
- Symptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Asymptomatic patients must be clinically stable with regard to their CNS/ meningeal metastatic involvement, have completed previous therapy (including radiation and/ or surgery) at least 4 weeks prior to study drug administration, are not receiving steroid therapy or taper, and are not receiving anti-convulsive medication for any CNS involvement
- Active infection requiring IV antibiotics
- Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of less than or equal to (</=) 10 mg/day prednisone
- Sensory peripheral neuropathy greater than or equal to (>/=) Grade 2
- Significant cardiovascular or cerebrovascular disease within 6 months prior to Day 1 of Cycle 1
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation
- Current use of anticoagulants at therapeutic doses within 7 days prior to study drug administration. Prophylactic use of unfractioned heparin or low molecular weight heparin is permitted
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to Day 1 of Cycle 1
- History of intra-abdominal inflammatory process within 6 months prior to Day 1 of Cycle 1 including but not limited to peptic ulcer disease, diverticulitis, or colitis
- Colonic prosthesis (stent) implant in place
- History of abdominal or tracheo-oesophageal fistula or gastrointestinal (GI) perforation or intra abdominal abscess within 6 months prior to Day 1 of Cycle 1
- History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or a requirement for routine parenteral hydration, parenteral nutrition, or tube feeding within 6 months prior to Day 1 of Cycle 1
- Chronic daily treatment with NSAID (occasional use for the symptomatic relief of medical conditions, for example headache or fever is allowed)
- Chronic daily treatment with corticosteroids (dose > 10 mg/day methylprednisolone equivalent) excluding inhaled steroids
- Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
- Metastatic disease that involve major airways or blood vessels, or centrally located mediastinal tumor masses (< 30 millimeter from the carina) of large volume
- History of bronchopulmonary hemorrhage NCI CTCAE >/= Grade 2 within 2 months prior to randomization
- Severe, nonhealing or open wound, active ulcer, or untreated bone fracture
- Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the patient for 5-FU toxicity
- Any other condition, diseases, metabolic dysfunction, active or uncontrolled infections/inflammation, physical examination finding, mental status or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates participation in the clinical study due to safety concerns, compliance with clinical study procedures or that may affect the interpretation of the results
Sites / Locations
- Alabama Oncology
- Arizona Clinical Research Ctr
- California Cancer Associates for Research & Excellence, Inc.
- Fresno cCare
- University of California San Diego Medical Center
- Va Greater Los Angeles Healthcare System
- SCRI Florida Cancer Specialists South
- Ocala Oncology Center
- Duke University Medical Center
- Oncology Hematology Care Inc
- Sarah Cannon Research Inst.
- Ctr for Cancer and Blood Disorders
- Cancer Therapy & Research Center
- Northern Utah Associates
- Calvary Mater Newcastle
- The Queen Elizabeth Hospital
- Monash Medical Centre-Moorabbin Campus
- Salzburger Landeskliniken LKH
- Oö. Gesundheits- und Spitals-AG/LKH Steyr
- Imeldaziekenhuis
- Centre Paul Papin
- Institut De Cancerologie De L'Ouest; Medical Oncology
- Hospital Universitario Germans Trias i Pujol
- Hospital Universitario Marques de Valdecilla
- Hospital Universitario Reina Sofia; Servicio de Oncologia
- Hospital del Mar; Servicio de Oncologia
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
- Hospital Clinic de Barcelona
- Institut Catala d Oncologia Hospital Duran i Reynals
- Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
- Hospital Universitario Clínico San Carlos; Servicio de Oncologia
- HM Sanchinarro - CIOCC; Servicio de Oncologia
- Hospital Universitario Virgen del Rocio
- Hospital Clinico Universitario de Valencia
- Aberdeen Royal Infirmary; Medical Oncology Dept
- Guys and St Thomas NHS Foundation Trust, Guys Hospital
- Maidstone Hospital
- Queen's Hospital; Oncology
- The Royal Marsden Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Active Comparator
Experimental
Active Comparator
Experimental
Part 1 (Induction): Vanucizumab + mFOLFOX-6
Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acid
Part 2 (Induction): Bevacizumab + mFOLFOX-6
Part 2 (Induction): Vanucizumab + mFOLFOX-6
Part 2 (Maintenance): Bevacizumab + 5-FU + Folinic acid
Part 2 (Maintenance): Vanucizumab + 5-FU + Folinic acid
Participants will receive vanucizumab at a dose of 2000 milligram (mg) as intravenous (IV) infusion; oxaliplatin at a dose of 85 mg per meter-squared (mg/m^2) as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).
Participants will receive vanucizumab at a dose confirmed during induction as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.
Participants will receive bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).
Participants will receive vanucizumab at a dose confirmed during part 1 as IV infusion; oxaliplatin at a dose of 85 mg/m^2 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).
Participants will receive bevacizumab at a dose of 5 mg/kg as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.
Participants will receive vanucizumab at a dose confirmed during part 1 as IV infusion; folinic acid at a dose of 400 mg/m^2 as IV infusion; and 5-FU at a dose of 400 mg/m^2 as starting IV bolus followed by 2400 mg/m^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.