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Trial registered on ANZCTR


Registration number
ACTRN12613000556741
Ethics application status
Approved
Date submitted
13/05/2013
Date registered
17/05/2013
Date last updated
14/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase III Randomized Study of BBI608 and Best Supportive Care versus Placebo and Best Supportive Care in Patients with Pretreated Advanced Colorectal Carcinoma
Scientific title
A randomised phase III double-blind study to evaluate the effect of BBI608 or placebo on overall survival in patients with pretreated advanced colorectal carcinoma
Secondary ID [1] 282510 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced (metastatic or locally advanced) colorectal cancer 288622 0
Condition category
Condition code
Cancer 288954 288954 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 286730 0
Treatment: Drugs
Comparator / control treatment
Group 2: Best supportive care plus Placebo. Best supportive care defined as those measures designed to provide palliation of symptoms and improve quality of life as much as possible. The matched placebo 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.
Control group
Placebo

Outcomes
Primary outcome [1] 289083 0
Overall survival (death from any cause)
Timepoint [1] 289083 0
Patient status updates will be sought every 2-4 weeks at clinic visit whilst on treatment and then every 8 weeks until death.
Secondary outcome [1] 301713 0
To evaluate progression free survival (disease progression or death) and objective response rate
Timepoint [1] 301713 0
Tumour response will be assessed according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1) guidelines via CT or MRI scan within 14 days prior to randomisation, and then every 8 weeks thereafter whilst the patients remain on study treatment.
Secondary outcome [2] 301714 0
Disease control rate (the proportion of patients with a documented complete response, partial response and stable disease (CR + PR + SD) based on RECIST 1.1 criteria)
Timepoint [2] 301714 0
Tumour response will be assessed according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1) guidelines via CT or MRI scan within 14 days prior to randomisation, and then every 8 weeks thereafter whilst the patients remain on study treatment.
Secondary outcome [3] 301715 0
Safety profile (adverse events graded according to NCI CTC AE Version 4.0)
Timepoint [3] 301715 0
Adverse events will be reported at baseline and assessed 4 weekly whilst on study treatment, at the 4 week safety assessment, and then every 8 weeks until deterioration to ECOG PS 4 or hospitalisation for end of life care.
Secondary outcome [4] 301716 0
Quality of Life (using EORTC QLQ-C30)
Timepoint [4] 301716 0
Patient rated quality of life will be assessed via self-report questionnaires at baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks and 24 weeks until deterioration to ECOG PS 4 or hospitalisation for end of life care.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
upon IDSMC review of the early interim analysis results advised that the study should be closed due to futility (ie: May 2014)
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 4938 0
Canada
State/province [1] 4938 0
Country [2] 4939 0
United States of America
State/province [2] 4939 0
Country [3] 4940 0
Japan
State/province [3] 4940 0

Funding & Sponsors
Funding source category [1] 286900 0
Other Collaborative groups
Name [1] 286900 0
Canadian Cancer Trials Group (CCTG)
Address [1] 286900 0
Cancer Clinical Trials Division
Cancer Research Institute
Queen's University
10 Stuart Street
Kingston, Ontario K7L 3N6
Country [1] 286900 0
Canada
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastro-Intestinal Trials Group
Address
Locked Bag 77
Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 285687 0
None
Name [1] 285687 0
Address [1] 285687 0
Country [1] 285687 0
Other collaborator category [1] 277321 0
University
Name [1] 277321 0
NHMRC Clinical Trials Centre
The University of Sydney
Address [1] 277321 0
Locked Bag 77
Camperdown NSW 1450
Country [1] 277321 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289256 0
Cancer Insitute New South Wales Clinical Research Ethics Committee
Ethics committee address [1] 289256 0
Level 9
8 Central Avenue
Australian Technology Park
Eveleigh

NSW 2015
Ethics committee country [1] 289256 0
Australia
Date submitted for ethics approval [1] 289256 0
11/03/2013
Approval date [1] 289256 0
Ethics approval number [1] 289256 0
2013C/03/214

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38494 0
Dr Louise Nott
Address 38494 0
c/o CO.23 Trial Coordinator
NHRMC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 38494 0
Australia
Phone 38494 0
+61 3 6222 8308
Fax 38494 0
Email 38494 0
louise.nott@dhhs.tas.gov.au
Contact person for public queries
Name 38495 0
Mr Eric Tsobanis
Address 38495 0
c/o CO.23 Trial Coordinator
NHRMC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 38495 0
Australia
Phone 38495 0
+61 2 9562 5000
Fax 38495 0
Email 38495 0
co.23@ctc.usyd.edu.au
Contact person for scientific queries
Name 38496 0
Mr Eric Tsobanis
Address 38496 0
c/o CO.23 Trial Coordinator
NHRMC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 38496 0
Australia
Phone 38496 0
+61 2 9562 5000
Fax 38496 0
Email 38496 0
co.23@ctc.usyd.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary