Background
Classification | Thickness (mm) | Ulceration status/Mitoses | |
---|---|---|---|
Tis | N/A | a | N/A |
T1 | Without ulceration and mitosis <1/mm2
| ||
b | With ulceration or mitosis ≥1/mm2
| ||
T2 | 1.01-2.00 | a | Without ulceration |
b | With ulceration | ||
T3 | 2.01-4.00 | a | Without ulceration |
b | With ulceration | ||
T4 | >4.00 | a | Without ulceration |
b | With ulceration | ||
N | No. metastatic nodes | Nodal metastatic burden | |
N0 | 0 | a | N/A |
N1 | 1 node involved | Micrometastases* | |
1 node involved | b | Macrometastases† | |
N2 | 2-3 nodes involved | a | Micrometastases |
2-3 nodes involved | b | Macrometastases | |
c | Intransit metastases/ satellites without metastatic nodes | ||
N3 | 4+ metastatic nodes or matted nodes or intransit metastases/satellites with metastatic nodes | ||
M | Site | Serum LDH | |
M0 | No distant metastases | N/A | |
M1a | Distant skin, subcutaneous or nodal metastases | Normal | |
M1b | Lung metastases | Normal | |
M1c | All other visceral metastases | Normal | |
Any distant metastasis | Elevated |
Stage | Primary tumour thickness and ulceration | Lymph node status | Distant metastasis |
---|---|---|---|
Stage 0 | Tis | N0 | M0 |
Stage IA | T1a | N0 | M0 |
Stage IB | T1b | N0 | M0 |
T2a | N0 | M0 | |
Stage IIA | T2b | N0 | M0 |
T3a | N0 | M0 | |
Stage IIB | T3b | N0 | M0 |
T4a | N0 | M0 | |
Stage IIC | T4b | N0 | M0 |
Stage IIIA | T1-4a | N1a | M0 |
T1-4a | N2a | M0 | |
Stage IIIB | T1-4b | N1a | M0 |
T1-4b | N2a | M0 | |
T1-4a | N1b | M0 | |
T1-4a | N2b | M0 | |
T1-4a | N2c | M0 | |
Stage IIIC | T1-4b | N1b | M0 |
T1-4b | N2b | M0 | |
T1-4b | N2c | M0 | |
Any T | N3 | M0 | |
Stage IV | Any T | Any N | M1a |
Any T | Any N | M1b | |
Any T | Any N | M1c |
Vitamin D
Vitamin D physiology
Serum measurement of vitamin D
Vitamin D and mortality
Vitamin D and cancer including melanoma
Raising 25OHD concentrations
Objectives of the present trial
Primary endpoints
-
If the majority of treated patients achieve a serum 25OHD of 80 nmol/l at both 12 and 24 months and the average serum 25OHD for treated patients is > 75 nmol/l at 12 and 24 months
-
If patients take > 80% of the prescribed monthly dose
-
Calcium [40]
-
■ If the mean serum calcium concentration in each patient is <2.75 mmol/L (11 mg/dL) over the course of the study.
-
■ If there is no increase in the prevalence of hypercalcaemia relative to the baseline prevalence.
-
■ If the urine calcium excretion in each patient is less than 7.5 mmol/24 h OR the mean urinary calcium-creatinine ratio in each patient is <1.0 (when calcium and creatinine are measured in mmol) over the course of the study.
-
■ If there is no increase in the prevalence of hypercalciuria relative to the baseline prevalence.
-
-
Kidney function
-
■ If there is no greater than a 20% fall in the average estimated GFR [GFR = 186.3 × SerumCr-1.154 × age-0.203 × 1.212 (if patient is black) × 0.742 (if female) – MDRD formula (21)] over the course of the study.
-
■ If the average eGFR at the end of the study is no more than 20% less in vitamin D treated patients than in placebo treated patients.
-
-
Renal calculi
-
If no more than two episodes of renal calculus occurs in vitamin D treated patients during the course of the study.
-
Secondary endpoints
Other tests
Methods/Design
Trial design
Participants
Intervention
Assessment of outcome
Baseline | 4-6 wks | 4 mth | 8 mth | 12 mth | 16 mth | 20 mth | 24 mth | |
---|---|---|---|---|---|---|---|---|
History
|
X
|
X
|
X
|
X
|
X
|
X
|
X
| |
Body mass index/height cm
|
X
|
X
|
X
|
X
|
X
|
X
|
X
| |
Serum corrected calcium
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
Phosphate
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
24 hour urinary calcium (preferred)
|
X
|
X
|
X
| |||||
Urinary calcium/creatinine ratio
(for first 3 time points only if 24 h urine unavailable)
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
Serum
25O D
|
X
|
X
|
X
|
X
|
X
| |||
FBC
|
X
|
X
|
X
|
X
| ||||
LFTs
|
X
|
X
|
X
|
X
| ||||
eGFR
|
X
|
X
|
X
|
X
| ||||
Adherence to dosing regime
|
X
|
X
|
X
|
X
|
X
|
X
|
X
| |
Tumour status
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
Sample size and randomisation
Accrual rate
Progression free survival
Participant follow-up
Blinding
Statistical methods
Quality assurance
Discussion
Feasibility
Registration
Protocol
Appendix 1
Comprehensive inclusion and exclusion criteria for ANZMTG 02.09 Mel-D study
Inclusion criteria
Exclusion criteria
Appendix 2
Safety procedures in the event of abnormal assay results
Dose modification
-
■ If serum 25OHD is >200 nmol/l 4–6 weeks after the first dose is given, discontinue all treatment and recommence monthly treatment if and when it falls to <120 nmol/l on 4 monthly monitoring.
-
■ If serum corrected calcium, 24 hour urinary calcium excretion or urinary calcium to creatinine ratio is above the normal range by <20% of the upper limit of normal, discontinue treatment until it returns to within the normal range, then recommence monthly treatment. In the event of temporary discontinuation for either of these reasons, measure 25OHD on stored serum from blood sample collected at the time of the elevated calcium or calcium to creatinine ratio if not a routine 25OHD measurement time.
Dose cessation
-
■ eGFR, serum corrected calcium, 24 hour urinary calcium excretion, or calcium to creatinine ratio is >20% above laboratory normal range.
-
■ Development of a renal calculus while on study treatment.
-
■ Pregnancy occurring during the course of the trial.
-
■ Disease progression.
Withdrawal because of low serum 25OHD concentration
Concomitant medications/treatments
-
■ Anti-convulsant medication is not allowed.
-
■ Any concomitant use of vitamin D or multi-vitamin supplements in sufficient detail to be able to estimate daily vitamin D intake from these sources.
-
■ Any concomitant use of calcium supplements.