Clinical trial NCT01478594 (phase 2, status: completed)
Conditions: colorectal cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: tivozanib, bevacizumab, mfolfox6
SMILES: COC1=C(OC)C=C2C(OC3=CC(Cl)=C(C=C3)N=C(O)N=C3NOC(C)=C3)=CC=NC2=C1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
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