BBI608 and Best Supportive Care vs Placebo and Best Supportive Care in Pretreated Advanced Colorectal Carcinoma
Condition: Colorectal Carcinoma
MeSH terms: Carcinoma; Colorectal Neoplasms
Intervention: BBI608; Placebo; Best Supportive Care
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 282.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to find out whether it is better to receive a new drug, BBI608,
      or better to receive no further treatment for colon or rectal cancer. To do this, half of the
      patients in this study will get BBI608 and the other half will receive a placebo (a substance
      that is designed not to do anything).
    

Eligibility criteria:

        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 regimen (e.g. 14 days for FOLFOX), prior to the first
             planned dose of BBI608/placebo. An exception is made for capecitabine and regorafenib,
             where a minimum of 10 days since last dose must be observed prior to the first planned
             dose of BBI608/placebo.

          -  Radiotherapy, immunotherapy, or investigational agents within four weeks of first
             planned dose of BBI608/placebo, with the exception of a single dose of radiation up to
             8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before
             randomization.

          -  Major surgery within 4 weeks prior to randomization.

          -  Any known symptomatic brain metastases requiring steroids.

          -  Women who are pregnant or breastfeeding.

          -  Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal
             Investigator, would significantly impede the absorption of an oral agent (e.g. active
             Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).

          -  Unable or unwilling to swallow BBI608/placebo capsules daily.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, clinically significant non-healing or healing wounds, symptomatic
             congestive heart failure, unstable angina pectoris, clinically significant cardiac
             arrhythmia, significant pulmonary disease (shortness of breath at rest or mild
             exertion), uncontrolled infection or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  Patients with a history of other malignancies except: adequately treated non-melanoma
             skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
             curatively treated with no evidence of disease for ≥ 5 years.

          -  Prior treatment with BBI608.

          -  Any active disease condition which would render the protocol treatment dangerous or
             impair the ability of the patient to receive protocol therapy.

          -  Any condition (e.g. psychological, geographical, etc.) that does not permit compliance
             with the protocol.