Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000769280
Ethics application status
Approved
Date submitted
1/09/2009
Date registered
4/09/2009
Date last updated
4/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised phase II trial of Cimetidine in patients having surgery for bowel cancer
Scientific title
A Randomised, Placebo-Controlled, Double-Blind Phase II Trial of the Effect of Peri-operative Cimetidine on Relapse and Survival in Early Colorectal Cancer
Secondary ID [1] 262690 0
U1111-1123-1396
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal cancer 243609 0
Condition category
Condition code
Cancer 239905 239905 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cimetidine oral tablets 800mg twice daily for 5 weeks starting a week before surgery
Intervention code [1] 241196 0
Treatment: Drugs
Comparator / control treatment
Placebo (content not specified) oral tablets 800mg twice daily for 5 weeks starting a week before surgery
Control group
Placebo

Outcomes
Primary outcome [1] 240687 0
2 year disease-free survival comparison by Kaplan-Meier actuarial survival curves and logrank statistic iin subgroup with positive tumour immunostaining for sialyl Lewis antigens a or x
Timepoint [1] 240687 0
primary outcome will be analysed when recruited population has been followed for a median of 2 years
Secondary outcome [1] 257320 0
duration of post-operative inflammatory cytokine elevation, assessed as the time that plasma concentrations of each cytokine (TNF, IL-1B, IL-6, IL-8) are elevated above pre-treatment baseline.
Timepoint [1] 257320 0
plasma concentrations of each cytokine will be measured at baseline (prior to starting study medication), the day prior to surgery then at 24 hours and 1, 2 and 4 weeks post-surgery
Secondary outcome [2] 257321 0
Prevalence of tumour sialyl Lewis antigen a and/or x expression overall (as % of cases scored as positive) and in different ethnic groups, using published immunostaining protocols
Timepoint [2] 257321 0
post-operative
Secondary outcome [3] 257322 0
Disease-free survival
Timepoint [3] 257322 0
once at 5 years median follow-up from recruitment
Secondary outcome [4] 257323 0
overall survival
Timepoint [4] 257323 0
once at 5 years median follow-up from recruitment
Secondary outcome [5] 257324 0
Cimetidine compliance (% of tablets taken of total expected in the period) and safety (proportion of patients with treatment-related adverse events)
Timepoint [5] 257324 0
Compliance is measured at the end of the first week, at discharge from hospital following surgery and 4 weeks after surgery.
Safety is assessed at the end of the first week of administration of study medication.

Eligibility
Key inclusion criteria
1. Biopsy-proven colorectal adenocarcinoma planned for resection with curative intent.
2. Age at least 18 years
3. Accessible for treatment and follow up
4. Written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinical T1 tumours such as a pedunculated polyp
2. Radiological or clinical evidence of unresectable primary tumours or metastatic disease beyond regional nodes
3. Unable to swallow or absorb study tablets
4. Currently taking H2-antagonists (cimetidine, ranitidine, famotidine, nizatidine)
5. Taking medications during the period of study treatment that have clinically significant interactions with cimetidine (including warfarin, phenytoin, theophylline and nifedipine)
6. Significantly impaired renal function (serum creatinine > 1.25 x upper limit of normal)
7. Significant liver impairment (bilirubin > 30 micromol/l; Alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper limit of normal)
8. Other invasive malignancy within 5 years except adequately-treated basal cell or squamous cell carcinoma of skin or in-situ carcinoma of the cervix
9. Pregnant or breast feeding women
10. Major surgery within prior 30 days, excluding defunctioning colostomy or ileostomy

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)
Consenting eligible patients will be enrolled through the Cancer Trials Unit at Waikato Hospital and allocated a subject number. They will be stratified by preoperative therapy (none vs chemoradiation or radiotherapy) and primary tumour site (colon vs rectum), then allocated by the Clinical Trials Pharmacist to cimetidine or placebo treatment using permuted block randomisation. Allocation concealment is achieved by each bottle being labelled with a batch number, expiry date, subject number and an individual bottle number (created from a list of random unique numbers). Batch numbers and expiry dates are the same for all medication bottles.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated random numbers for each stratum
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Chemotherapy and/or radiotherapy prior to, or following, surgery will be administered according to local policies
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/03/2010
Actual
3/03/2010
Date of last participant enrolment
Anticipated
Actual
17/12/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment outside Australia
Country [1] 1966 0
New Zealand
State/province [1] 1966 0

Funding & Sponsors
Funding source category [1] 237554 0
Charities/Societies/Foundations
Name [1] 237554 0
Waikato Medical Research Foundation
Country [1] 237554 0
New Zealand
Funding source category [2] 237555 0
Charities/Societies/Foundations
Name [2] 237555 0
Cancer Society of NZ (Waikato-Bay of Plenty Division)
Country [2] 237555 0
New Zealand
Primary sponsor type
Hospital
Name
Waikato Hospital
Address
Private Bag 3200
Hamilton 3240
Country
New Zealand
Secondary sponsor category [1] 237030 0
None
Name [1] 237030 0
Address [1] 237030 0
Country [1] 237030 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 243688 0
Northern Y Regional Ethics Committee
Ethics committee address [1] 243688 0
PO Box 1031
Hamilton
Ethics committee country [1] 243688 0
New Zealand
Date submitted for ethics approval [1] 243688 0
04/09/2009
Approval date [1] 243688 0
03/11/2009
Ethics approval number [1] 243688 0

Summary
Brief summary
This study is looking at how we can most effectively use Cimetidine, an ulcer-healing drug that has been available for over 30 years, to try to improve the outcome in patients having surgery to remove bowel cancer. This drug can support the immune system to remain fully active following the stress of surgery, and might reduce the risk of cancer cells spreading during and after the operation. However it is not clear how long patients may need to take the drug to gain the maximum benefit, and this study is aiming to clarify that by examining the impact of surgery on immune responses and what effect cimetidine has on them.

We will randomise patients to take cimetidine or placebo tablets twice a day for 5 weeks, starting a week before the operation, and will look at immune responses in blood tests taken 6 times over those 5 weeks. We will also look at whether patients have any problems taking the tablets, especially immediately after the operation, how well they recover from surgery and whether they have recurrence of the bowel cancer over the next few years.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30099 0
Dr Michael Jameson
Address 30099 0
Regional Cancer Centre Waikato Hospital Private Bag 3200 Hamilton 3240
Country 30099 0
New Zealand
Phone 30099 0
+64 7 839 8604
Fax 30099 0
Email 30099 0
[email protected]
Contact person for public queries
Name 13346 0
Wendy Thomas
Address 13346 0
Cancer Trials Unit
Waikato Hospital
Private Bag 3200
Hamilton 3240
Country 13346 0
New Zealand
Phone 13346 0
+64 7 839 8976
Fax 13346 0
+64 7 858 0940
Email 13346 0
[email protected]
Contact person for scientific queries
Name 4274 0
Michael Jameson
Address 4274 0
Regional Cancer Centre
Waikato Hospital
Private Bag 3200
Hamilton 3240
Country 4274 0
New Zealand
Phone 4274 0
+64 7 839 8604
Fax 4274 0
+64 7 839 8778
Email 4274 0
[email protected]

No information has been provided regarding IPD availability


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
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