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Trial registered on ANZCTR


Registration number
ACTRN12619000210178
Ethics application status
Approved
Date submitted
2/01/2019
Date registered
13/02/2019
Date last updated
13/02/2019
Date data sharing statement initially provided
13/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Colonisation of Probiotic in Neoplasia.
Scientific title
Assessing the colonisation of a conventional probiotic in the neoplastic and normal human tissue of patients undergoing surgical procedures
Secondary ID [1] 296901 0
None
Universal Trial Number (UTN)
U1111-1225-7729
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 310848 0
Condition category
Condition code
Cancer 309525 309525 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The probiotic is Escherichia coli Nissle 1917 (EcN), supplied as Mutaflor, Ardeypharm. Each tablet contains at least 5x108 colony forming units (CFU) EcN.
Participants will take either 2 tablets of probiotic or placebo (sugar pill) per day for 14 to 28 days, prior to surgery or colonoscopy. Previous studies have administered probiotic for 28 days. This has been shown to be a safe human dose in earlier phase I trials that unfortunately did not measure colonisation as an end-point. The duration of intervention will depend upon the time participants are consented before their procedure (at least 14 days).
Adherence of the intervention will be monitored by probiotic tablet return.
Mutaflor and placebo tablets are provided for free from Ardeypharm.
Intervention code [1] 313174 0
Early detection / Screening
Intervention code [2] 313521 0
Treatment: Other
Comparator / control treatment
The placebo is completely identical to the Mutaflor capsule without containing EcN. The missing volume due to the absence of the active ingredient EcN is replaced by a corresponding additional amount of maltodextrin.
Participants will be randomly assigned: 50% to probiotic treatment and 50% to placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 308473 0
Neoplastic colonisation as assessed by DNA sequencing of surplus pathology tissue.
Timepoint [1] 308473 0
5 years post-enrolment.
Secondary outcome [1] 355105 0
Tumour genetics associated with colonisation will be assessed by DNA sequencing of surplus pathology tissue. DNA sequencing will assess mutations in clinically actionable CRC-associated genes, such as BRAF, KRAS, EGFR, NRAS and MSI markers. This outcome is exploratory.
Timepoint [1] 355105 0
3 months post-sample collection
Secondary outcome [2] 366356 0
Microbiome associated with colonisation assessed by DNA sequencing of surplus pathology tissue. This outcome is exploratory.
Timepoint [2] 366356 0
3 months post-sample collection

Eligibility
Key inclusion criteria
Participants must be 18 years or older and undergoing endoscopic polyp removal or surgical resection by the CRC team at the Royal Adelaide Hospital or St Andrew's Hospital in >2 weeks. Participants will most likely have confirmed cancer by pathology but can also be included if pathology is inconclusive but mass is being resected. Previous treatment or radiation to the tumour site is permissible for this study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants must not be currently taking probiotics or antibiotics.

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)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Bio-availability
Statistical methods / analysis
1. 22 consecutive patients diagnosed with primary colonic cancer (n=11 right-sided and n=11 left-sided)
2. 22 consecutive adult patients diagnosed with primary rectal cancer undergoing short-course pre-operative radiotherapy
3. 22 consecutive adult patients with colorectal cancer liver metastasis.
4. 44 consecutive patients with precancerous colonic lesions (n=22 right-sided and n=22 left-sided)
50% of patients in each group (1-4 above) will be randomly assigned to probiotic treatment, 50% to placebo.
We expect a 10% drop-out rate of participants from this study eg if the participant requires antibiotics during the trial, postponement of surgery or if participant decides to withdraw. As such we will recruit 22 participants for each group to enable collection from 20 participants/group. A group size of 20 (for groups 1-4 above), allowing 10 participants on placebo, 10 on probiotic was determined based on the experience of our microbiome team with a number of factors. These include participant to participant and gut location variability in probiotic colonisation efficiency. The probiotic colonisation efficiency of normal vs neoplastic human colon is not known (indeed this is why we are doing this study) and so is difficult to accurately estimate. From our mouse work using genetically identical animals on a controlled diet, there is a greater than 10,000-fold increase in probiotic bacteria levels in neoplastic tissue.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
25/02/2019
Actual
Date of last participant enrolment
Anticipated
14/11/2022
Actual
Date of last data collection
Anticipated
14/11/2027
Actual
Sample size
Target
110
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 12766 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 12767 0
St Andrew's Hospital Inc - Adelaide
Recruitment postcode(s) [1] 25207 0
5000 - Adelaide
Recruitment postcode(s) [2] 25208 0
5000 - Hutt Street

Funding & Sponsors
Funding source category [1] 301434 0
Charities/Societies/Foundations
Name [1] 301434 0
Cancer Council SA - Beat Cancer Project
Country [1] 301434 0
Australia
Primary sponsor type
Individual
Name
SAHMRI
Address
SAHMRI location: North Tce, Adelaide, SA, 5000

Postal address: PO Box 11060, Adelaide, SA 5001
Country
Australia
Secondary sponsor category [1] 301230 0
None
Name [1] 301230 0
Address [1] 301230 0
Country [1] 301230 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302225 0
CALHN HREC
Ethics committee address [1] 302225 0
Ethics committee country [1] 302225 0
Australia
Date submitted for ethics approval [1] 302225 0
12/11/2018
Approval date [1] 302225 0
19/01/2019
Ethics approval number [1] 302225 0
HREC/18/CALHN/751 CALHN ref: R20181115

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89354 0
A/Prof Daniel Worthley
Address 89354 0
Gastrointestinal Cancer Biology Group
Level 5S, SAHMRI
North Tce
Adelaide, SA, 5000
Country 89354 0
Australia
Phone 89354 0
+61 400363208
Fax 89354 0
Email 89354 0
Dan.Worthley@sahmri.com
Contact person for public queries
Name 89355 0
Daniel Worthley
Address 89355 0
Gastrointestinal Cancer Biology Group
Level 5S, SAHMRI
North Tce
Adelaide, SA, 5000
Country 89355 0
Australia
Phone 89355 0
+61 400363208
Fax 89355 0
Email 89355 0
Dan.Worthley@sahmri.com
Contact person for scientific queries
Name 89356 0
Daniel Worthley
Address 89356 0
Gastrointestinal Cancer Biology Group
Level 5S, SAHMRI
North Tce
Adelaide, SA, 5000
Country 89356 0
Australia
Phone 89356 0
+61 400363208
Fax 89356 0
Email 89356 0
Dan.Worthley@sahmri.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified age, sex, stage, histology, location of lesion, previous history of bowel cancer and previous treatment may be shared.
When will data be available (start and end dates)?
With publication (no end date).
Available to whom?
Anyone who wishes to access it.
Available for what types of analyses?
Any purpose.
How or where can data be obtained?
Scientifically reviewed journal publication that will be available on the internet.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.