A Study of BBI608 Administrated With FOLFIRI + Bevacizumab in Adult Patients With Metastatic Colorectal Cancer

Inclusion criteria

• A histologically confirmed advanced unresectable, metastatic or recurrent colorectal carcinoma
• Evaluable patient by RECISTversion 1.1
• Stage IV
• ≥ 20 years of age
• Life expectancy ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Patients with following organ function within 14 days before enrollment (on the basis of the most recent data during the period if multiple data are available)

• Hemoglobin (Hg) ≥ 9.0 g/dL
• Neutrophil count ≥ 1.5 x 103/μL
• Platelet count ≥ 10 x 104/μL
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases ]
• Total bilirubin ≤ 1.5 × institutional ULN [≤ 2 × ULN in presence of liver metastases ]
• Creatinine ≤ 1.5 × institutional ULN
• Proteinuria by dipstick urine analysis ≤ 1+. [ UPCR (Urine Albumin-to-Creatinine Ratio) ≤ 1, or protein volume of 24-hour urine collection ≤ 1 g, in the case of patients with a 2+ urine dipstick reading]
• For female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose or 6 months after Bevacizumab treatment.. For male patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 90 days after the last protocol treatment dose or 6 months after Bevacizumab treatment
• Females of childbearing potential have a negative urine pregnancy test
• Patients who have provided written voluntary consent in person to participate in this study after fully receiving and understanding the information about this study, including study

Exclusion criteria

• Anti-cancer chemotherapy, radiotherapy, immunotherapy, or hormone therapy, or heart therapy within 21 days of the first dose of BBI608
• Major surgery within 28 days prior to first dose
• Have had a brain metastases with a symptom or requiring treatment
• Have had coinstantaneously active multiple primary cancer
• Have had a carcinomatous pleural effusion, ascites, or cardiac effusion requiring treatment
• Crohn's disease, ulcerative colitis, small intestine resection, diarrhea (watery diarrhea), paralysis intestinal, Intestinal obstruction
• Gastrointestinal perforation, tracheo-oesophageal fistula, fistula
• Unable or unwilling to swallow BBI608 capsules
• Uncontrolled inter-current illness (such as Grade 3 active infection, or serious respiratory disease)
• Uncontrolled hypertension
• Patients with recent history of hemoptysis of more than 2.5 mL of red blood within 28days before the enrolment
• Abnormal ECGs which are clinically significant within 28 days before enrolment
• Patients who are New York Heart Association (NYHA) functional classes III, or IV, or unstable angina
• Patients newly expressing angina within three months (90 days) before the enrolment
• Have had myocardial infarction within six months (180 days)before the enrolment
• Administrating with antiarrhythmic drug
• Patients who are planning to breast-feeding by whichever 30 days after the last administration of BBI608 or by 6 months after the last administration of Bevacizumab
• Patients of pregnancy or possibility of pregnancy at current time or possibility of pregnancy within 6 months after the last administration of Bevacizumab
• Have received other investigational products or not finished the assessment in any clinical study within 28 days before enrollment
• Known severe hypersensitivity to 5-FU/ levofolinate/ irinotecan/Bevacizumab
• Administration of atazanavir sulfate
• Prior treatment with BBI608
• Ineligible for participation in the study in the opinion of the Investigators