A Study Combining mFOLFOX6 With Tivozanib or Bevacizumab in Patients With Metastatic Colorectal Cancer as First Line Therapy
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Tivozanib; Bevacizumab; mFOLFOX6
Intervention description: Capsules for oral administration; Solution for intravenous infusion; mFOLFOX6 regimen is a combination therapy of oxaliplatin 85 mg/m^2 administered as an intravenous bolus over 2 hours on Days 1 and 15, leucovorin calcium 400 mg/m^2 administered as an intravenous bolus over 2 hours on Days 1 and 15, fluorouracil 400 mg/m^2 administered as an intravenous bolus over 5 to 15 minutes on Days 1 and 15, then 2400 mg/m^2 continuous intravenous infusion over 46 hours on Days 1 to 3 and 15 to 17.
Intervention MeSH terms: Bevacizumab; Tivozanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 265.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic colorectal cancer; Avastin; bevacizumab; tivozanib; mFOLFOX6; BATON-CRC; AV951; ASP4130

Summary:

      The objective of this study is to compare the progression free survival (PFS), overall
      survival (OS), objective response rate (ORR), time to treatment failure (TTF), duration of
      response (DoR), quality of life, safety and tolerability of tivozanib in combination with
      mFOLFOX6 and bevacizumab in combination with mFOLFOX6.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented diagnosis of metastatic colorectal cancer

          -  One measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

          -  No prior systemic chemotherapy for advanced colorectal cancer; no fluorouracil
             containing adjuvant therapy in previous 6 months

          -  Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

        Exclusion Criteria:

          -  Any prior Vascular Endothelial Growth Factor (VEGF)-directed therapy or any other
             agent or investigational agent targeting the VEGF pathway

          -  Primary Central Nervous System (CNS) malignancies or CNS metastases

          -  Hematologic abnormalities:

               -  Hemoglobin < 9.0 g/dL,

               -  Absolute neutrophil count (ANC) < 2000 per mm^3,

               -  Platelet count < 100,000 per mm^3,

               -  Prothrombin (PT) or Partial Thromboplastin Time (PTT) > 1.5 X Upper Limit of
                  Normal (ULN)

          -  Serum chemistry abnormalities:

               -  Total bilirubin > 1.5 X ULN,

               -  Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) > 2.5 X ULN,

               -  Alkaline phosphatase > 2.5 X ULN,

               -  Serum albumin < 2.0 g/dL,

               -  Creatinine > 1.5 X ULN,

               -  Proteinuria > 2+ by urine dipstick

          -  Significant cardiovascular disease

          -  Significant thromboembolic or vascular disorders within 6 months prior to
             administration of first dose of study drug

          -  Non-healing wound, bone fracture, or skin ulcer

          -  Inadequate recovery from any prior surgical procedure or major surgical procedure
             within 8 weeks prior to administration, or anticipation of major surgical procedure
             during the course of the study

          -  History of significant gastrointestinal (GI) toxicity, diarrhea, or stomatitis within
             the last 6 weeks

          -  An active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or
             other gastrointestinal condition with increased risk of perforation

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 4 weeks prior to administration of first dose of study drug

          -  Serious/active infection or infection requiring antibiotics

          -  Significant bleeding disorders within 6 months prior to administration of first dose
             of study drug

          -  Active second primary malignancy, other than non-melanoma skin cancers, non-metastatic
             prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of
             the breast. Subject is not considered to have a currently active malignancy if they
             have completed anti-cancer therapy and have been disease free for > 5 years

          -  History of allergic reactions, or intolerance, attributed to compounds of similar
             chemical or biologic composition to 5-fluorouracil, history of Grade 3
             hypersensitivity to oxaliplatin, history of allergic reaction to folic acid

          -  Female subject is pregnant or lactating

          -  Known history of genetic or acquired immune suppression disease including Human
             Immunodeficiency Virus (HIV); subjects on immune suppressive therapy for organ
             transplant

          -  Inability to swallow pills, malabsorption syndrome or gastrointestinal disease, major
             resection of the stomach or small bowel, or gastric bypass

          -  Uncontrolled neuro-psychiatric disorder or altered mental status

          -  Peripheral neuropathy ≥ Grade 2

          -  Participating in another interventional protocol