Trial Review

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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
4/11/2022
Date data sharing statement initially provided
4/11/2022
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
Cohort 1
Arm 1: sodium selenite taken orally at doses of 400 mcg elemental selenium daily for eight weeks
Arm 2: L-selenomethionine taken orally at doses of 400 mcg elemental selenium daily for eight weeks
Arm 3: Se-methyl-selenocysteine taken orally at doses of 400 mcg elemental selenium daily for eight weeks.
Cohort 2
Arm 1: sodium selenite taken orally dosed at 1600 mcg of elemental selenium daily for 4 weeks then escalating to 6400mcg daily for a further 4 week in absence of dose-limiting toxicities
Arm 2: L-selenomethionine taken orally dosed at 1600 mcg of elemental selenium daily for 4 weeks then escalating to 6400mcg daily for a further 4 week in absence of dose-limiting toxicities
Arm 3: Se-methyl-selenocysteine taken orally dosed at 1600 mcg of elemental selenium daily for 4 weeks then escalating to 6400mcg daily for a further 4 week in absence of dose-limiting toxicities.
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
Assessment now at baseline, 4 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
Sex
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 for 400mcg dose and ( n=6 ) for intra-patient dose escalation phase 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
1/04/2014
Actual
11/02/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
42
Accrual to date
24
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
Country [1] 286634 0
New Zealand
Funding source category [2] 286635 0
Charities/Societies/Foundations
Name [2] 286635 0
Cycle for Life
Country [2] 286635 0
New Zealand
Funding source category [3] 286636 0
Hospital
Name [3] 286636 0
Waikato District Health Board
Country [3] 286636 0
New Zealand
Funding source category [4] 286637 0
Commercial sector/Industry
Name [4] 286637 0
Sabinsa Corporation
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
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
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
[email protected]
Contact person for public queries
Name 37399 0
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
[email protected]
Contact person for scientific queries
Name 37400 0
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
[email protected]

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 participant data underlying published results
When will data be available (start and end dates)?
After publication and available for at least 1 year
Available to whom?
Case by case basis at the discretion of the primary sponsor
Available for what types of analyses?
To achieve aims in the approved proposal.
How or where can data be obtained?
On request from the Principal Investigator:
Dr. Michael Jameson at [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17533Study protocol  [email protected]
17534Ethical approval  [email protected]
17535Statistical analysis plan  [email protected]
17536Informed consent form  [email protected]



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseComparative Safety and Pharmacokinetic Evaluation of Three Oral Selenium Compounds in Cancer Patients.2019https://dx.doi.org/10.1007/s12011-018-1501-0
N.B. These documents automatically identified may not have been verified by the study sponsor.