Topical Vitamin D3, Diclofenac or a Combination of Both to Treat Basal Cell Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01358045
First received: May 17, 2011
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

Basal cell carcinoma (BCC) is the most frequent malignant tumor in Caucasians and the incidence is still increasing with 3-8% each year. Since BCCs generally occur on sun-exposed areas of the skin, the rice in incidence is mainly explained by the increasing exposure to (intermittent) ultraviolet radiation. Surgical excision is still the standard treatment for (micro)nodular BCCs. The costs as well as the increased workload are stressing the health care system even further and posing BCC an important health care problem. Since half of the BCCs arise primarily on the face & (bald) head and treatment by surgical excision may result in disfiguring scars, patients often experience a dramatic decrease of their quality of life. Hence, there is an urgent medical and societal need for a simple and cheap (targeted) treatment, preferably to be performed by the patients themselves. This treatment must be safe and effective. Such treatment is not available yet. BCC tumorigenesis is complex and must be multifactorial. Genetic alterations of multiple components of the Sonic Hedgehog (SHH) pathway are involved in sporadic BCC pathogenesis; inactivating mutations in Patched-1 (PTCH1) and activating mutations of Smoothened (SMO) and Suppressor of Fused (SU(FU)). With this knowledge, inhibition of the SHH pathway by SMO antagonists was successfully administered, however treatment resulted only in partial clinical response ofBCC. Recently, involvement of the Wingless (Wnt) pathway has been proven to be essential in BCC tumorigenic response. Moreover, a recent study of our own department provides the first evidence that epigenetic alterations, particularly promoter hypermethylation, influence both the SHH and Wnt pathway (own data, not published), which can serve as therapeutic targets. Both non-steroidal anti-inflammatory drugs (NSAlDS) and vitamin D derivatives are able to directly or indirectly target the Wnt pathway. Furthermore, vitamin D3 is able to inhibit Smoothened (SMO) in vitro, resulting in inhibition of the SHH pathway. Although in vivo studies are lacking, the investigators assume that topical application of these drugs may inhibit BCC growth and/or may cure BCC and thus might provide very promising future perspectives. Calcitriol and NSAlDs ointments are both already available for other indications and save in use. Eventually, our approach may result in a systematic approach to BCC, targeting (epi)genetic changes to treat and/or prevent further tumour growth.


Condition Intervention Phase
Basal Cell Carcinoma
Drug: Diclofenac
Drug: Diclofenac + Calcitriol
Drug: Calcitriol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Topical Vitamin D3, Diclofenac or a Combination of Both to Treat Basal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Histological changes in different proliferation, apoptosis and autophagy markers. [ Time Frame: At baseline and after 8 weeks. ] [ Designated as safety issue: No ]
    To determine whether topical application of Calcitriol (Silkis) 3 μg/g, Diclofenac 3% or a combination of both can lead to a 40% histological reduction (↓)/increase (↑) of expression of the following antibodies: Ki67 (↓), BCL2 (↓), CASPASE 3 (↑) and Cox2 (↓) (proliferation and apoptosis), LC3B (↑) (autophagy), HIF1α (↓) (hypoxia), β-catenin (↓), sFRP4 (↑) and sFRP5 (↑) (Wnt pathway activity).


Secondary Outcome Measures:
  • Macroscopic tumour changes [ Time Frame: Baseline and after 8 weeks. ] [ Designated as safety issue: Yes ]
    We want the observe if the tumour will also macroscopically change within 8 weeks of treatment. Things were we will focus on will be size and colour.

  • Toleration [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    We want to evaluate if the patients will tolerate the therapy. Main points in here will be irritation of the skin and the amount of time this therapy costs the patients.

  • Safety [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    We want to evaluate if the treatment is safe and does not lead to a lot of side effects.


Enrollment: 128
Study Start Date: November 2011
Study Completion Date: May 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Solaraze Drug: Diclofenac
Application on the lesion 2 times a day 8 weeks.
Other Name: Solaraze
Active Comparator: Solaraze + Silkis Drug: Diclofenac + Calcitriol
Application on the lesion 2 times a day, both ointments, 8 weeks.
Other Name: Solaraze + Silkis
Active Comparator: Silkis Drug: Calcitriol
Application on the lesion, 2 times a day, 8 weeks.
Other Name: Silkis
No Intervention: No treatment

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Minimum age 18 years
  • Primary basal cell carcinoma, histologically confirmed
  • (Micro) Nodular or superficial histological subtype
  • Comorbidities may not interfere with study treatment
  • Capable to understand instructions

Exclusion Criteria:

  • Age under 18 years
  • Tumors located at the H-zone of the face
  • Deficient histological conformation
  • Proven or suspected malignancy of other organs
  • Not capable of comprehending instructions
  • Incompetent
  • Use of oral NSAlDs during the trial period or within 30 days before starting therapy
  • Use of oral vitamin D (containing) supplements during the trial period or within 30 days before starting therapy
  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: NCT01358045

Locations
Netherlands
Maastricht University Medical Center
Maastricht, Limburg, Netherlands, 6202 AZ
Sponsors and Collaborators
Maastricht University Medical Center
  More Information

No publications provided

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01358045     History of Changes
Other Study ID Numbers: MEC 10-2-088
Study First Received: May 17, 2011
Last Updated: March 18, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
Topical
Diclofenac
Vitamin D3

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Basal Cell
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Basal Cell
Neoplasms, Glandular and Epithelial
Calcitriol
Cholecalciferol
Diclofenac
Vitamin D
Vitamins
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Bone Density Conservation Agents
Calcium Channel Agonists
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Growth Substances
Membrane Transport Modulators
Micronutrients
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents

ClinicalTrials.gov processed this record on October 30, 2014