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

NCT01358045 | Completed Phase 2 DMC

• 1 other identifier: MEC 10-2-088
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Basal Cell Carcinoma

Keywords

Topical; Diclofenac; Vitamin D3

Outcome Measures

Primary Outcomes (1)

• Histological changes in different proliferation and apoptosis markers.

  To determine the change in mean percentage of cells expressing Ki67 and BCL2 after topical application of Calcitriol (Silkis) 3 μg/g, Diclofenac 3% or a combination of both.

  At baseline and after 8 weeks.

Secondary Outcomes (3)

• Macroscopic tumour changes

  Baseline and after 8 weeks.

• Toleration

  8 weeks

• Compliance

  8 weeks

Study Arms (4)

Solaraze

ACTIVE COMPARATOR

Drug: Diclofenac

Solaraze + Silkis

ACTIVE COMPARATOR

Drug: Diclofenac + Calcitriol

Silkis

ACTIVE COMPARATOR

Drug: Calcitriol

No treatment

NO INTERVENTION

Interventions

Diclofenac DRUG

Application on the lesion 2 times a day 8 weeks.

Also known as: Solaraze

Solaraze

Diclofenac + Calcitriol DRUG

Application on the lesion 2 times a day, both ointments, 8 weeks.

Also known as: Solaraze + Silkis

Solaraze + Silkis

Calcitriol DRUG

Application on the lesion, 2 times a day, 8 weeks.

Also known as: Silkis

Silkis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, Limburg, 6202 AZ, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Basal Cell

Interventions

Diclofenac; Calcitriol

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2011
• First Posted: May 23, 2011
• Study Start: November 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 13, 2015

Record last verified: 2015-01

Locations

NL (1)