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Trial registered on ANZCTR


Registration number
ACTRN12613000118707
Ethics application status
Approved
Date submitted
29/01/2013
Date registered
31/01/2013
Date last updated
24/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised trial to identify the safest and most effective selenium compound for cancer patients
Scientific title
Phase Ib randomised double-blind dose-escalation study to identify the safest, most effective selenium compound for use in cancer patients
Secondary ID [1] 281854 0
Nil
Universal Trial Number (UTN)
U1111-1138-9924
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 288216 0
Condition category
Condition code
Cancer 288581 288581 0 0
Leukaemia - Chronic leukaemia
Cancer 288582 288582 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: sodium selenite taken orally at doses of 400, 1600 or 6400 mcg elemental selenium daily for eight weeks
Arm 2: L-selenomethionine taken orally at doses of 400, 1600 or 6400 mcg elemental selenium daily for eight weeks
Arm 3: Se-methyl-selenocysteine taken orally at doses of 400, 1600 or 6400 mcg elemental selenium daily for eight weeks
The 3 dose levels within each arm represent separate cohorts.
Intervention code [1] 286412 0
Treatment: Other
Comparator / control treatment
The three arms are being compared as well as the doses within each arm. In addition each patient serves as their own control.
Control group
Active

Outcomes
Primary outcome [1] 288738 0
Safety and tolerability of each selenium compound at the evaluated doses as assessed by compliance with study medication and occurrence of adverse events (graded using CTCAE version 4) on clinical, laboratory and electrocardiographic assessments
Timepoint [1] 288738 0
At baseline then 1 day and 4, 8 and 12 weeks after commencing treatment
Secondary outcome [1] 300866 0
Plasma concentrations of selenium achieved with oral administration of the three selenium compounds at each dose
Timepoint [1] 300866 0
At baseline then 1 day and 4, 8 and 12 weeks after commencing treatment
Secondary outcome [2] 300867 0
Dose-response of the three selenium compounds with respect to pharmacodynamic markers:
1. endoplasmic reticulum stress response assessed by western blotting in peripheral blood mononuclear cells
2. DNA damage assessed by COMET assay in peripheral blood mononuclear cells
3. angiogenesis assessed by plasma ELISA assay
4. plasma glutathione peroxidase activity assessed by colorimetric assay
5. intracellular glutathione concentrations in peripheral blood mononuclear cells assessed by colorimetric assay

Timepoint [2] 300867 0
Twice at baseline (a week apart) then 1 day and 4, 8 and 12 weeks after commencing treatment
Secondary outcome [3] 300868 0
Tumour response as assessed by serum tumour markers (where relevant) in cancer patients and peripheral blood counts of atypical lymphocytes in patients with chronic lymphocytic leukaemia
Timepoint [3] 300868 0
Twice at baseline (a week apart) then 1 day and 4, 8 and 12 weeks after commencing treatment
Secondary outcome [4] 300869 0
The relationship between dose, plasma selenium concentrations and pharmacodynamic markers of each compound in normal and malignant peripheral blood mononuclear cells
Timepoint [4] 300869 0
On completion of recruitment and all study procedures
Secondary outcome [5] 300870 0
Speciation of selenium compounds in plasma, urine and peripheral blood mononuclear cells using various chromatography and mass spectrometry methods
Timepoint [5] 300870 0
Baseline and 8 weeks after starting treatment

Eligibility
Key inclusion criteria
1. Subjects with either chronic lymphocytic leukaemia (peripheral blood lymphocyte count > 10 x 10^9/l) or metastatic cancer, in whom the use of chemotherapy is not anticipated in the next 3 months
2. Adequate liver, renal and bone marrow function
3. ECOG performance status 0-2
4. Life expectancy over 6 months
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects treated within the last 4 weeks with cytotoxic chemotherapy, anticancer biological therapy (excluding hormonal therapy for prostate cancer) or radiotherapy
2. Unable to swallow or absorb study tablets
3. Concurrent selenium supplements over 100 mcg/day

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)
Permuted block randomisation conducted by the Clinical Trials Pharmacist at Waikato Hospital; randomisation lists will only be available to the pharmacist.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated random number sequence with stratification by cancer type
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Dose-escalation: subjects will be randomised between the three treatment arms at the lowest dose level; escalation to the next dose level is permitted if no dose-limiting toxicity is seen in more than one of eight subjects in each compound-dose cohort.
Pharmacokinetic and pharmacodynamic endpoints also.
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Subjects will be grouped together (n=8) in each dose cohort for safety and pharmacokinetic analyses. Analysis of relationships between dose, plasma selenium concentration and changes in pharmacodynamic markers in the different groups will be conducted using repeated measures analysis of variance methods or linear mixed modelling methods. Fisher’s exact test will be used to compare frequency of adverse events.

Recruitment
Recruitment status
Recruiting
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 outside Australia
Country [1] 4826 0
New Zealand
State/province [1] 4826 0

Funding & Sponsors
Funding source category [1] 286634 0
Charities/Societies/Foundations
Name [1] 286634 0
Genesis Oncology Trust
Address [1] 286634 0
P O Box 17188
Greenlane
Auckland 1546
Country [1] 286634 0
New Zealand
Funding source category [2] 286635 0
Charities/Societies/Foundations
Name [2] 286635 0
Cycle for Life
Address [2] 286635 0
C/o TCA Gym
210 Jellicoe Crescent
Thames 3540
Country [2] 286635 0
New Zealand
Funding source category [3] 286636 0
Hospital
Name [3] 286636 0
Waikato District Health Board
Address [3] 286636 0
Private Bag 3200
Hamilton 3240
Country [3] 286636 0
New Zealand
Funding source category [4] 286637 0
Commercial sector/Industry
Name [4] 286637 0
Sabinsa Corporation
Address [4] 286637 0
20 Lake Drive
East Windsor
NJ
08520
Country [4] 286637 0
United States of America
Primary sponsor type
Hospital
Name
Waikato District Health Board
Address
Private Bag 3200
Hamilton 3240
Country
New Zealand
Secondary sponsor category [1] 285419 0
None
Name [1] 285419 0
Address [1] 285419 0
Country [1] 285419 0
Other collaborator category [1] 277270 0
University
Name [1] 277270 0
University of Waikato
Address [1] 277270 0
Private Bag 3105
Hamilton 3240
Country [1] 277270 0
New Zealand
Other collaborator category [2] 277802 0
University
Name [2] 277802 0
University of Surrey
Address [2] 277802 0
Guildford
Surrey
GU2 7XH
Country [2] 277802 0
United Kingdom
Other collaborator category [3] 277803 0
Government body
Name [3] 277803 0
LGC Limited
Address [3] 277803 0
Queens Road
Teddington
Middlesex
TW110LY
Country [3] 277803 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288713 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 288713 0
C/o Ministry of Health
P O Box 5013
Wellington 6145
Ethics committee country [1] 288713 0
New Zealand
Date submitted for ethics approval [1] 288713 0
12/06/2012
Approval date [1] 288713 0
06/11/2013
Ethics approval number [1] 288713 0
13/NTA/172

Summary
Brief summary

Selenium is a trace mineral commonly taken by people hoping to prevent or treat cancer. However certain types of selenium could be harmful, especially at the high doses that show promise in reducing side effects of radiotherapy or chemotherapy without reducing their effectiveness. It is important to know which form of selenium can be most safely used at higher doses and have the best effect. In this clinical research study we will compare the effects of three different types of selenium in people with cancer or chronic lymphocytic leukaemia, looking at their safety and beneficial effects on the cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37398 0
Dr Michael Jameson
Address 37398 0
Oncology Dept
Waikato Hospital
Private Bag 3200
Hamilton 3240
Country 37398 0
New Zealand
Phone 37398 0
+64 7 839 8899
Fax 37398 0
+64 7 839 8778
Email 37398 0
michael.jameson@waikatodhb.health.nz
Contact person for public queries
Name 37399 0
Dr Michael Jameson
Address 37399 0
Oncology Dept
Waikato Hospital
Private Bag 3200
Hamilton 3240
Country 37399 0
New Zealand
Phone 37399 0
+64 7 839 8899
Fax 37399 0
+64 7 839 8778
Email 37399 0
michael.jameson@waikatodhb.health.nz
Contact person for scientific queries
Name 37400 0
Dr Michael Jameson
Address 37400 0
Oncology Dept
Waikato Hospital
Private Bag 3200
Hamilton 3240
Country 37400 0
New Zealand
Phone 37400 0
+64 7 839 8899
Fax 37400 0
+64 7 839 8778
Email 37400 0
michael.jameson@waikatodhb.health.nz

No information has been provided regarding IPD availability
Summary results
No Results