MelaViD: A Trial on Vitamin D Supplementation for Resected Stage II Melanoma Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by European Institute of Oncology
Sponsor:
Information provided by (Responsible Party):
European Institute of Oncology
ClinicalTrials.gov Identifier:
NCT01264874
First received: December 21, 2010
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

The purpose of this trial is to assess the effect of vitamin D supplementation on recurrence in resected stage II melanoma patients.


Condition Intervention Phase
Melanoma
Drug: Vitamin D3 ( Colecalciferol)
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase III, Randomized, Double Blind Trial on Vitamin D Supplementation for Resected Stage II Melanoma Patients

Resource links provided by NLM:


Further study details as provided by European Institute of Oncology:

Primary Outcome Measures:
  • Disease free survival and Overall Survival [ Time Frame: 3 years of treatment and 2 of follow up ] [ Designated as safety issue: No ]

    Disease free survival (DFS) will be the primary end-point of efficacy in this Phase III trial. It will be measured from the date of randomization to the date of progression or death, whatever the cause.

    Overall Survival will be also evaluated and it is defined as the time from the date of randomization to the date of death from any cause or to the date of last follow-up.



Secondary Outcome Measures:
  • Evaluation of Vitamin D receptors and 25(OH)D by Breslow thickness. [ Time Frame: baseline and after 1 year of treatment ] [ Designated as safety issue: No ]

    Evaluation at baseline of Vitamin D receptors and 25(OH)D by Breslow thickness. Change in time of 25(OH)D serum level by VDR and other genes involved in vitamin D metabolisms.

    Percentages of patients at desired levels of 25(OH)D (30 ng/ml) during 1 year. Toxicity.

    Compliance. OS.



Estimated Enrollment: 878
Study Start Date: May 2010
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vitamin D3
Vitamin D3 administration
Drug: Vitamin D3 ( Colecalciferol)
100000 IU every 50 days for 3 years
Other Name: dibase
Placebo Comparator: placebo
matched placebo
Other: placebo
For 3 years IU every 50 days

Detailed Description:

Cancer chemoprevention uses natural, synthetic, or biologic chemical agents to reverse, suppress, or prevent carcinogenic progression (Sporn MB Cancer Res 1976). Genetic changes exist throughout the field and increase the likelihood that one or more premalignant and malignant lesions may develop within that field. Multistep carcinogenesis describes a stepwise accumulation of alterations, both genotypic and phenotypic. Arresting one or several of the steps may impede or delay the development of cancer. Several epidemiological, pre-clinical and clinical studies support Vitamin D as preventive and therapeutic cancer agent, for a wide spectrum of cancer. Calcitriol (1,25-dihydroxyvitamin D [1,25(OH) D]), the hormonal derivative of vitamin D, has been established since the 1980s as an antiproliferative and prodifferentiation agent, and as a proapoptotic agent and an inhibitor of cell migration, which may imply an inhibitory effect in cancer. Vitamin D is more like a hormone and not strictly a vitamin according to the classical criteria that an essential nutrient is a substance the body cannot synthesise in sufficient quantities itself. Also, vitamins are usually involved in biochemical reactions, while 1_,25-dihydroxyvitamin D exerts its action via VDR. Vitamin D is a group of fat-soluble prohormones, the two major forms of which are vitamin D2 (or ergocalciferol) and vitamin D3 (or cholecalciferol). Endogenous synthesis of vitamin D3 takes place in the skin under the influence of ultra violet B (UVB) radiation. Exogenous vitamin D2 or D3 comes from dietary intake. The overall vitamin D intake is the sum of cutaneous vitamin D and nutritional vitamin D and D. Vitamin D on its own has no physiological action. To be physiologically active, vitamin D must first be hydroxylated in the liver by the enzyme 25-hydroxylase, encoded by CYP27A1 (also called the 25-hydroxylase) in 25-hydroxyvitamin D or 1,25-hydroxyvitamin D (1,25-hydroxyvitamin D). The 25-hydroxyvitamin D is inactive, and an additional hydroxylation in the kidney by the enzyme 1_-hydroxylase, encoded by CYP27B1, (also called 1_-hydroxylase) is necessary for production of the physiologically active vitamin D metabolite, the 1_,25-dihydroxyvitamin D (calcitriol). When 1,25(OH) D is sufficiently available, the enzyme mitochondrial protein encoded by CYP24A1 metabolises the 1_,25-dihydroxyvitamin D in 1_,24,25-dihydroxyvitamin D, which is further catabolised to calcitroic acid. 25(OH)D and 1,25(OH)2D are transported in serum by the vitamin D-binding protein (gene name: GC, group-specific component). Ahn systematically investigated the association of 48 SNPS in four vitamin D metabolizing genes (CYP27A1, GC, CYP27B1, and CYP24A1) with serum 25(OH)D levels. Four tagSNPS in GC, the major serum 25(OH)D carrier, were associated with 25(OH)D levels (Ahn et al.Carcinogenesis 2009). CYP24A1 encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This mitochondrial protein initiates the degradation of 1,25-dihydroxyvitamin D by hydroxylation of the side chain. In regulating the level of vitamin D, this enzyme plays a role in calcium homeostasis and the vitamin D endocrine system. Of interest, epigenetic silencing of CYP24A1, which is overexpressed in many cancers, in tumour-derived endothelial cells renders the tumour sensitive to the anti-angiogenic effects of 1,25(OH) D. Various molecules can inhibit 24-Ohase. These merit exploration and further development as specific small molecule 24-OHase inhibitors, especially in combination with 1,25(OH)D or other vitamin D analogues. These may maximize intracellular 1,25(OH)D content and exert optimal antiproliferative effects (Deeb 2007; Mantell 2000; Nishimura 1994). Binding of 1,25(OH)D to the vitamin D receptor (VDR) suppresses proliferation and induces differentiation of cancer cells in tumour tissue, suggesting that high levels of vitamin D metabolites may be protective against cancer (Deeb 2007; Reichel 1989).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18-75 years old with newly diagnosed histologically proven resected melanoma
  2. Stage: IIa (T2b, T3a), IIb (T3b T4a) and IIc (T4b), N0, M0
  3. Signed informed Consent
  4. Willingness to provide blood samples
  5. Performance Status of 0-1
  6. Hematopoietic functionality at the entry of the study: leukocytes, platelets, haemoglobin and neutrophiles within the normal limits of laboratory references
  7. Hepatic and renal functionality at the entry of the study within the normal range of each laboratory
  8. Serum and urinary calcium within the upper limit of laboratory references.

Exclusion Criteria:

  1. Primary not cutaneous melanoma
  2. Clinical/radiological evidence or laboratory/pathology report of not completely resected melanoma
  3. History of cancer (other than Carcinoma in situ (CIN) and non melanoma skin cancere (NMSC)
  4. Current daily use of at least 600 IU/day of supplemental vitamin D or calcitriol or high dose of calcium therapy (e.g. calcium citrate with vitamin D) within the prior 6 months greater than 600 mg calcium per day during study
  5. History of recurrent renal calculi or hypercalcemia (>10mg/dl), current and chronic use of oral corticosteroids
  6. History of malabsorption syndrome (e.g., pancreatic insufficiency, celiac disease, Crohn disease or tropical sprue)
  7. History of small intestinal resection (e.g., ileal bypass surgery for treatment of morbid obesity resection > 50 % of slim bowel)
  8. Hypersensitivity to cholecalciferol or one of its components
  9. Chronic liver disease, chronic renal disease, or renal dialysis
  10. History of parathyroid disease and sarcoidosis
  11. Pregnancy or breast feeding or planning on becoming pregnant during the 3 years of treatment
  12. Chronic alcoholism
  13. Any medical condition that in the physician's opinion would potentially interfere with vitamin D absorption, such as celiac sprue, ulcerative colitis, patients treated pharmacologically for obesity
  14. Any logistic condition that do not allow follow-up of the disease of the patient.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01264874

Contacts
Contact: Alessandro Testori, MD alessandro.testori@ieo.it
Contact: Sara Gandini, PhD sara.gandini@ieo.it

Locations
Italy
European Institute of Oncology Recruiting
Milan, Italy, 20141
Principal Investigator: Alessandro Testori, MD         
Sponsors and Collaborators
European Institute of Oncology
Investigators
Principal Investigator: Alessandro Testori, MD European Institute of Oncology
  More Information

No publications provided

Responsible Party: European Institute of Oncology
ClinicalTrials.gov Identifier: NCT01264874     History of Changes
Other Study ID Numbers: S480/209, 2009-012049-46
Study First Received: December 21, 2010
Last Updated: June 17, 2014
Health Authority: Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Cholecalciferol
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014