Clinical trial NCT02029352: Topical Green Tea Ointment in Treatment of Superficial Skin Cancer
Official title: Topical Sinecatechins Ointment in Treatment of Primary Superficial Basal Cell Carcinoma: a Double Blind, Randomized, Placebo-controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Carcinoma, Basal Cell
Keywords: Treatment
Sinecatechins
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Will-Pharma
name: Medigene AG
First posted: 2014-01-07
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Basal cell carcinoma (BCC) is the most frequently occurring nonmelanoma skin cancer in Caucasians, representing approximately 80% of cases. Incidence rates for men and women in the Netherlands are 165 and 157 per 100,000 person-years respectively and are still rising 3-10% annually. In 2009, the lifetime risk for developing a first histologically confirmed BCC for men was approximately 1 in 5 (21%) and for women it was 1 in 6 (18%).

A simplified classification of BCC includes the following three histological subtypes: nodular (40,6), superficial (30,7%) and infiltrative BCC (28,7%). Superficial BCCs (sBCCs) differ from the other subtypes as they tend to appear at a younger age, usually occur on the trunk and are often multiple. This subtype has the fastest growing incidence.

A characteristic feature of BCCs is their low risk to metastasize, though if untreated they may induce considerable functional and cosmetic morbidity as they are locally invasive. Surgery is the first treatment of choice for BCC. However due to the rising incidence and the extensive workload this entails, a non-invasive topical treatment is often chosen for sBCC as they grow down from the epidermis into the superficial dermis and therefore are easily accessible for topical treatment. Photodynamic therapy (PDT), imiquimod cream or 5-fluorouracil cream are available topical treatments for sBCC however their tumour free survival rates are not equal to the higher tumour free survival rates of surgical treatment. Next to the efficacy, the now available topical treatments are associated with local skin reactions at the treatment site, mainly erythema and erosion (imiquimod cream and 5-fluorouracil cream) or pain and burning sensation (PDT). This creates the need for additional or alternative non-invasive topical treatments.

The active constituents of green tea are promising as they are supported to have anti-BCC-carcinogenesis effects by several epidemiological, cell culture and animal studies. The so-called polyphenols known as catechins are the active constituents of green tea and the catechin epigallocatechin-3-gallate (EGCG) is the major and most active catechin. EGCG is thought to have a cytotoxic effect on skin cancer cells and has the availability of inhibition of cell growth and induction of apoptosis. It is also suggested that EGCG plays a role in inactivation of β-catenin signalling, an important component of the WNT pathway.

Sinecatechins 10% ointment (Veregen®) is a standardized extract of green tea leaves of the species Camellia sinensis, containing mainly green tea polyphenols, particularly catechins (more than 85%). The lead catechin in sinecatechins ointment is EGCG. It is approved by the US Food and Drug Administration (FDA) for genital warts in adults.

There are no clinical trials on human subjects with topical EGCG on sBCC yet. With this trial we are the first to try to validate the anti-carcinogenic potentials of topical EGCG in humans with sBCC. We assess the effectiveness of sinecatechins 10% (Veregen®) versus placebo for the topical treatment of sBCCs.


Eligibility criteria: Inclusion Criteria:

* Adults aged 18 years or older
* Primary histological proven superficial basal cell carcinoma ≥ 4mm and ≤ 20mm
* Comorbidities may not interfere with study treatment (evaluated by investigator)
* Capable to understand instructions

Exclusion Criteria:

* Recurrent sBCC (previous treatment)
* Breast-feeding or pregnant women
* Serious comorbidities
* Use of immunosuppressive medication during the trial period or within 30 days before enrolment
* Patients with genetic skin cancer disorders
* Tumour located in the H zone (high-risk area of face) or scalp

Primary outcomes:
measure: Percentage of patients with complete histological clearance
timeFrame: After 6 weeks treatment
Secondary outcomes:
measure: Number of applications actually done by the patient divided by the total prescribed number of applications.
timeFrame: Week 6
measure: Number of local skin reactions, adverse events and serious adverse events
timeFrame: Up to 3 weeks
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
Study officials:
affiliation: Maastricht University Hospital
name: Nicole WJ Kelleners-Smeets, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Katiyar SK, Matsui MS, Elmets CA, Mukhtar H. Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin. Photochem Photobiol. 1999 Feb;69(2):148-53.
citation: Singh T, Katiyar SK. Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting beta-catenin signaling. Toxicol Appl Pharmacol. 2013 Dec 1;273(2):418-24. doi: 10.1016/j.taap.2013.09.021. Epub 2013 Oct 3.
citation: Tyring SK. Effect of Sinecatechins on HPV-Activated Cell Growth and Induction of Apoptosis. J Clin Aesthet Dermatol. 2012 Feb;5(2):34-41.
citation: Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 1998 Apr;19(4):611-6. doi: 10.1093/carcin/19.4.611.