BBI608 and Best Supportive Care vs Placebo and Best Supportive Care in Pretreated Advanced Colorectal Carcinoma

Inclusion Criteria

• Histologically confirmed advanced colorectal cancer that is unresectable.
• Received a prior thymidylate synthase inhibitor (e.g. 5-fluorouracil (5-FU), capecitabine, raltitrexed, UFT) for metastatic disease or as adjuvant therapy.
• Received and failed an irinotecan containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease, OR relapsed within 6 months of completion of an irinotecan-containing adjuvant therapy, OR have documented unsuitability for an irinotecan-containing regimen.
• Received and failed an oxaliplatin-containing regimen for treatment of metastatic disease, OR relapsed within 6 months of completion of an oxaliplatin-containing adjuvant therapy OR have documented unsuitability for an oxaliplatin-containing regimen.
• For patients with colorectal cancer that is K-ras wild type: Received and failed a cetuximab or panitumumab-containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease OR have documented unsuitability for a cetuximab or panitumumab-containing regimen
• The only remaining standard available therapy as recommended by the Investigator is best supportive care.
• Must have presence of measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
• Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease done within 14 days prior to randomization.
• Must have an ECOG Performance Status of 0 or 1.
• Must be ≥ 18 years of age.
• For male or 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.
• Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to randomization.
• Must have alanine transaminase (ALT) ≤ 3 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases] within 14 days prior to randomization.
• Must have hemoglobin (Hgb) ≥ 80 g/L within 14 days prior to randomization.
• Must have total bilirubin ≤ 1.5 × institutional ULN [≤ 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.
• Must have creatinine ≤ 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min within 14 days prior to randomization.
• Must have absolute neutrophil count ≥ 1.5 x 109/L within 14 days prior to randomization.
• Must have platelet count ≥ 75 x 109/L within 14 days prior to randomization.
• Other biochemistry which must be done within 14 days prior to randomization includes lactate dehydrogenase (LDH) and alkaline phosphatase.
• Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit at the request of the NCIC CTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays may be conducted.
• Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.
• Patient is able (i.e. sufficiently fluent) and willing to complete the Quality of Life and Health Utilities questionnaires in one of the validated languages for the questionnaires.
• Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial.
• Protocol treatment is to begin within 2 working days of patient randomization.
• The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other clinical studies during their participation in this trial while on study treatment.

Exclusion Criteria

• Anti-cancer chemotherapy or biologic therapy within the lesser of i) 21 days, or ii) the usual cycle length of the