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Trial registered on ANZCTR


Registration number
ACTRN12609000351213
Ethics application status
Approved
Date submitted
4/05/2009
Date registered
25/05/2009
Date last updated
9/07/2019
Date data sharing statement initially provided
9/07/2019
Date results information initially provided
9/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Vitamin D following primary treatment of melanoma at high risk of recurrence
Scientific title
Assessing the feasibility, safety and toxicity of vitamin D following primary treatment of melanoma at high risk of recurrence: A pilot placebo controlled randomised phase II trial
Secondary ID [1] 884 0
ANZMTG 02-09
Universal Trial Number (UTN)
Trial acronym
Mel-D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cutaneous malignant melanoma 4712 0
Condition category
Condition code
Cancer 5034 5034 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral vitamin D3 tablets (Calciferol D Forte 1.25mg) 50 000IU or matching placebo administered during first study visit post-randomisation (10 tablets administered in total). Thereafter, self-adminstration of one vitamin D3 tablet (Calciferol D Forte) 50 000IU by patients on first day of every month for 23 months.
Intervention code [1] 4479 0
Treatment: Drugs
Comparator / control treatment
Placebo (Sugar pill)
Control group
Placebo

Outcomes
Primary outcome [1] 5873 0
Dose sufficiency : At 12 and 24 months, most treated patients achieve a serum 25 hydroxy vitamin D (25OH D) of 80nmol/l and the average serum 25 hydroxy vitamin D (25OH D) for treated patients is >75nmol/l.

Assays and diagnostic tests will be performed at timepoints to measure serum 25 hydroxy vitamin D (25OH D) level.
Timepoint [1] 5873 0
At baseline, 4, 12 and 24 months post-randomisation
Primary outcome [2] 5928 0
Dose compliance: On average, patients take >80% of prescribed monthly dose.

The study team willl confirm compliance to treatment by contacting study patients at interim periods during the treatment phase and also during 4 monthly follow-up visits. Additionally, patients will be asked to keep a diary to record their use of the study drug. These diaries will be reviewed on a 4 monthly basis at follow-up visits.
Timepoint [2] 5928 0
Baseline visit plus every 4 months for 2 years
Primary outcome [3] 5929 0
Safety:

i) Calcium - Over the course of the study, the mean serum calcium concentration in each patient is <2.75mmol/l (11mg/dl).

There is no increase in the prevalence of hypercalcaemia relative to the baseline prevalence.

Over the course of the study, the mean urinary calcium to creatinine ratio in each patient is <1.0 (when calcium and creatinine are measured in nmol).

There is no increase in the prevalence of hypercalciuria relative to the baseline prevalence.

ii) Renal - Over the course of the study, the decrease in average estimated Glomerular Filtration Rate (eGFR) is no more than 20%.

At the end of the study, the average estimated Glomerular Filtration Rate (eGFR) is no more than 20% less in vitamin D treated patients than in placebo treated patients.

iii) Renal calculi - During the course of the study, no more than two episodes of renal calculus occuring in vitamin D treated patients.

Assays and diagnostic tests would be performed to measure (i)-(iii). These include:
- Renal and liver function tests (including estimated Glomerular Filtration Rate (eGFR) and urine calcium/creatinine ratio)
- Serum 25 hydroxy vitamin D (25OH D) levels
- Serum corrected calcium levels
Timepoint [3] 5929 0
i) Calcium - Baseline visit plus every 4 months for 2 years

ii) Renal - Baseline visit plus every second study visit (i.e. at 8, 16 and 24 months)

iii) Renal Calculi - Baseline visit plus every 4 months for 2 years
Secondary outcome [1] 241901 0
Participation rate: 60% of patients who are both eligible and invited agree to participate.

Participation rate will be monitored and reported as the proportion of subjects eligible and invited agree to participate.
Timepoint [1] 241901 0
At the end of the study
Secondary outcome [2] 241903 0
Progression free survival.

Monitoring for recurrence will continue as per standard practice of the monitoring institute and also during the 4 monthly follow-up visits.
Timepoint [2] 241903 0
Baseline visit plus every 4 months for 2 years

Eligibility
Key inclusion criteria
i) Primary, histologically confirmed resected stage IIb, IIc, IIIa (N1a) and IIIb (N1a, N2a) cutaneous melanoma

ii) Wide excision or if there is no wide excision, excision of the primary lesion with clear pathological marigins <90 days prior to randomisation

iii) Serum corrected calcium and urinary calcium to creatinine ratio within normal range for testing laboratory

iv) Serum creatinine <=1.5 times the institutional upper limit of normal and estimated Glomerular Filtration Rate (eGFR) within normal range for testing laboratory.

v) Serum Low-density Lipoprotein <1.5 upper limit of normal (ULN)

vi) Able to provide written informed consent

vii) Geographically accessible and willing and able to attend 4 monthly folllow-up visits at Sydney Melanoma Unit (SMU) for 2 years

viii) Performance status - Eastern Cooperative Oncology Group (ECOG) score between 0 and 2
Minimum age
18 Years
Maximum age
79 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) Patients with a known history of renal calculi

ii) Patients with a known history of hyperthyroidism

iii) Patients who have a concomitant invasive cancer other than basal cell carcinoma of the skin or localised squamous cell carcinoma of the skin or a previous such cancer and have been cancer free for less than 5 years

iv) Any of the following laboratory results (tests must not have been carried out more than 4 weeks prior to randomisation)

Absolute neutrophil count (ANC) <1.5 x 10 (to the power of 9)/l
Platelet count <100 x 10 (to the power of 9)/l
Total bilirubin >1.5 upper limit of normal (ULN)
Aspartate Amino Transferase (AST), Alanine Amino Transferase (ALT), Alkaline Phosphate (Alk Phos) >2.5 upper limit of normal (ULN)

v) Patients who are pregnant or lacatating. Women of child bearing potential must have a confirmed negative pregnancy test at study entry

vi) Patients with a medical or psychological problem which, in the investigators' opinion, would interfere with treatment or follow-up

vii) Patients with either ocular or mucosal melanoma

viii) Patients who are currently enrolled in other concurrent experimental treatments or alternative therapies

ix) Patients cannot have received any other investigational agents or treatment (i.e. chemo, immuno, vaccine or radio therapy) within 30 days of commencing study

x) Patients should not be taking other agents known to interact with the study drug such as anti-convulsants

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)
The randomisation process will be coordinated centrally and sites will phone to request randomisation for a patient and confirm eligibility information by fax. Once randomised, the investigator and patient will be made aware of the study kit number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified allocation, gender will be used for stratification.

Manual telephone randomisation will be used to randomise patients.
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
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
NSW
Recruitment hospital [1] 2916 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 2917 0
The Poche Centre, Melanoma Institute Australia - North Sydney
Recruitment postcode(s) [1] 8640 0
2050 - Missenden Road
Recruitment postcode(s) [2] 8641 0
2060 - North Sydney

Funding & Sponsors
Funding source category [1] 4943 0
Charities/Societies/Foundations
Name [1] 4943 0
Melanoma Institute Australia
Address [1] 4943 0
The Poche Centre
40 Rocklands Road North Sydney NSW 2060
Country [1] 4943 0
Australia
Funding source category [2] 4944 0
Government body
Name [2] 4944 0
Cancer Institute NSW
Address [2] 4944 0
Australian Technology Park
Biomedical Building
Suite 101
1 Central Avenue (off Garden Road)
Eveleigh NSW 2015
Country [2] 4944 0
Australia
Funding source category [3] 4945 0
Commercial sector/Industry
Name [3] 4945 0
Blackmores Pty Ltd
Address [3] 4945 0
20 Jubilee Avenue
Warriewood NSW 2102
Country [3] 4945 0
Australia
Funding source category [4] 4963 0
Commercial sector/Industry
Name [4] 4963 0
Australia Post
Address [4] 4963 0
P O Box 1018
Strawberry Hills NSW 2012
Country [4] 4963 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australia and New Zealand Melanoma Trials Group
Address
The Poche Centre
40 Rocklands Road North Sydney NSW 2060
Country
Australia
Secondary sponsor category [1] 4534 0
None
Name [1] 4534 0
Address [1] 4534 0
Country [1] 4534 0
Other collaborator category [1] 659 0
University
Name [1] 659 0
National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC)
Address [1] 659 0
6-10 Mallett St
Camperdown NSW 2050
Country [1] 659 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6954 0
Sydney Local Health District
Ethics committee address [1] 6954 0
Research Development Office Royal Prince Alfred Hospital Missenden Road Camperdown NSW 2050
Ethics committee country [1] 6954 0
Australia
Date submitted for ethics approval [1] 6954 0
01/07/2009
Approval date [1] 6954 0
27/08/2009
Ethics approval number [1] 6954 0
HREC/09/RPAH/213

Summary
Brief summary
This study aims to evaluate the safety and efficacy of high dose vitamin D therapy in patients who have primary melanoma which has been treated and are at high risk of recurrence. Who is it for? You may be eligible to join this study if you aged 18 to 79 years and have been diagnosed with cutaneous melanoma. Study details: Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will receive vitamin D3 tablets monthly for 24 months, whilst participants in the other group will receive a placebo (sugar pill). Participants will be followed-up for 24 months, in order to determine dose sufficiency, compliance, safety and progression free survival.
Trial website
http://www.anzmtg.org/trialdetails.aspx?trialno=12
Trial related presentations / publications
Available in the ANZMTG website - http://www.anzmtg.org/trialdetails.aspx?trialno=12
Public notes

Contacts
Principal investigator
Name 29563 0
Dr Robyn Saw
Address 29563 0
The Poche Centre
40 Rocklands Road North Sydney NSW 2060
Country 29563 0
Australia
Phone 29563 0
+ 61 2 9911 7210
Fax 29563 0
+ 61 2 9954 9418
Email 29563 0
Robyn.Saw@melanoma.org.au
Contact person for public queries
Name 12810 0
Mr Alan Lucas
Address 12810 0
The Poche Centre
40 Rocklands Road North Sydney NSW 2060
Country 12810 0
Australia
Phone 12810 0
+ 61 2 9911 7352
Fax 12810 0
+ 61 2 9954 9435
Email 12810 0
Mel-D@melanoma.org.au
Contact person for scientific queries
Name 3738 0
Dr Dr Robyn Saw
Address 3738 0
The Poche Centre
40 Rocklands Road North Sydney NSW 2060
Country 3738 0
Australia
Phone 3738 0
+ 61 2 9911 7210
Fax 3738 0
+ 61 2 9954 9418
Email 3738 0
Robyn.Saw@melanoma.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
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