None listed
Conditions
Brief summary
This study will evaluate the effect of a drug called BBI608, a cancer stem cell inhibitor, for treatment of advanced colorectal cancer. Who is it for? You may be eligible to join this study if you are aged 18 years or above and have been diagnosed with advanced colorectal cancer for which no further standard anticancer therapy is appropriate or available. Trial Details: Participants in this trial will be randomly (by chance) allocated to one of two groups. Participants will either take BBI608 (Group 1) or a placebo (sham) (Group 2) tablets twice per day in continuous 28 day cycles. Treatment will continue for as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and are, in the opinion of the investigator, continuing to benefit from therapy. Participants will not know whether they are taking BBI608 or the placebo until after the trial is completed. Participants will be followed up every 4 weeks in order to evaluate how they are responding to treatment.
Interventions
Group 1: Best supportive care plus BBI608. Best supportive care defined as those measures designed to provide palliation of symptoms and improve quality of life as much as possible. BBI608 will be self-administered by participants at 480mg (6 x 80mg tablets) orally twice daily (960mg total daily dose) in 28 day cycles. Patients may continue to receive protocol therapy as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and are, in the
Group 1: Best supportive care plus BBI608. Best supportive care defined as those measures designed to provide palliation of symptoms and improve quality of life as much as possible. BBI608 will be self-administered by participants at 480mg (6 x 80mg tablets) orally twice daily (960mg total daily dose) in 28 day cycles. Patients may continue to receive protocol therapy as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and are, in the opinion of the investigator, continuing to derive benefit from protocol therapy. Patients will be asked to keep a diary of when they take the capsules and if they miss any doses to monitor adherance. Patients will also be asked to return any tablets which were not taken.
Sponsors
Australasian Gastro-Intestinal Trials Group
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed, written informed consent 2. Must have histologically confirmed advanced (metastatic or locally advanced) colorectal cancer that is unresectable 3. Received a prior thymidylate synthase inhibitor (e.g. 5-fluorouracil (5-FU), capecitabine, raltitrexed, UFT) for metastatic disease or as adjuvant therapy. Thymidylate synthase inhibitor may have been given in combination with oxaliplatin or irinotecan 4. 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 5. Received and failed an oxaliplatin-containing regimen (i.e. single-agent or in combination) 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 6. 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 7. The only remaining standard available therapy as recommended by the Investigator is best supportive care. 8. Must have presence of measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1) 9. Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease done within 10. Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 11. Must be greater or equal to 18 years of age 12. 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 13. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to randomization. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG 14. Must have alanine transaminase (ALT) < 3 × institutional upper limit of normal (ULN) [< 5 × ULN in presence of liver metastases] 15. Must have hemoglobin (Hgb) > 80 g/L 16. Must have total bilirubin < 1.5 × institutional ULN [< 2.0 x ULN in presence of liver metastases] 17. Must have creatinine < 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min 18. Must have absolute neutrophil count > 1.5 x 109/L 19. Must have platelet count > 75 x 109/L 20. Other biochemistry which must be done includes lactate dehydrogenase (LDH) and alkaline phosphatase 21. 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 22. Patients must be accessible for treatment and follow up 23. Protocol treatment is to begin within 2 working days of patient randomization 24. The patient is not receiving therapy in a concurrent clinical study
Exclusion criteria
1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks of first dose 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 2. Major surgery within 4 weeks prior to randomization 3. Any known symptomatic brain metastases requiring steroids 4. Women who are pregnant or breastfeeding 5. 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) 6. Unable or unwilling to swallow BBI608/placebo capsules daily 7. 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 8. Prior treatment with BBI608 9. Any active disease condition or intercurrent illness which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy or that would limit compliance with study requirements 10. Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol
Outcome results
None listed