To Evaluate the Safety, Local Tolerability, PK and PD of LDE225 on Sporadic Superficial and Nodular Skin Basal Cell Carcinomas(sBCC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01033019
First received: December 15, 2009
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

A double-blind, randomized, vehicle-controlled Proof of Concept (PoC) study to evaluate the efficacy, safety, local tolerability, pharmacokinetics and pharmacodynamics of multiple topical administrations of LDE225 (a specific Smoothened inhibitor) on sporadic superficial and nodular skin basal cell carcinomas (superficial, sBCC) The study will consist of a 21-day screening period and a treatment period of 6 weeks ending with post treatment biopsies, followed by a safety visit one week after final drug administration (Day 50) and then by excision of the sBCC (Day 83) and a Study Completion evaluation (Day 90).

Patients will be exposed to multiple doses of topically applied LDE225 twice daily for 6 weeks in a double-blind manner. LDE225 and the vehicle as a negative control, will be randomized to the test areas. Shave biopsy may be performed pre-treatment to confirm diagnosis. Following the last application of the treatment, punch biopsies will be taken from the sBCC for biomarker and pharmacokinetics (lesional and perilesional) evaluation. In total 4 biopsies will be taken.

During treatment, the patients will return weekly for visits where each treated sBCC will be clinically evaluated and digital photographs taken. Local safety and tolerability will also be assessed.


Condition Intervention Phase
Sporadic Superficial and Nodular Skin Basal Cell Carcinomas
Drug: LDE225
Drug: Vehicle
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double-blind, Randomized, Vehicle-controlled Proof of Concept Study on the Efficacy, Safety, Local Tolerability, PK and Pharmacodynamics of Multiple Topical Administrations of LDE225 on Sporadic Superficial and Nodular Skin Basal Cell Carcinomas

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Clinical evaluation of sBCCs tumors (complete response, partial response, no response / worsening) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serious adverse events, adverse events, local tolerability [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
  • Histological signs of tumor regression; apoptosis, tumor proliferation markers in sBCC [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Specific biomarkers related to the Smo pathway (Gli1, Gli2, Ptch1 and Ptch2) in BCC tumor tissue and expression of Gli1 by immunohistochemistry [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • LDE225 pharmacokinetics in plasma and skin [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: December 2009
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDE225
LDE225
Drug: LDE225
Placebo Comparator: Vehicle (Placebo Comparator)
Placebo
Drug: Vehicle

  Eligibility

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

Inclusion Criteria:

  • Patients with one histologically confirmed superficial and nodular basal cell carcinoma (8-20 mm) eligible for surgical excision on selected body areas (scalp, arm, frontal trunk, posterior trunk, upper legs)

Exclusion Criteria:

  • Previous treatment of the sBCC that are selected for treatment.
  • Any systemic treatment which is known to affect BCCs esp. cytostatic treatments, retinoids and photodynamic treatments.
  • Dark-skinned persons whose skin color prevents readily assessment of skin reactions

Other protocol defined Incl./Excl. criteria may apply.

  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: NCT01033019

Locations
Australia
Novartis Investigative Site
Benowa, Australia
Novartis Investigative Site
Woolloongabba, Australia
Austria
Novartis Investigative Site
Graz, Austria
Novartis Investigative Site
Wien, Austria
United Kingdom
Novartis Investigative Site
Manchester, United Kingdom
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01033019     History of Changes
Other Study ID Numbers: CLDE225B2204, EudraCT 2009-013665-26
Study First Received: December 15, 2009
Last Updated: March 6, 2014
Health Authority: Austria: Federal Office for Safety in Health Care
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Basal cell carcinomas,
sporadic,
superficial and nodular,
skin

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Basal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Basal Cell

ClinicalTrials.gov processed this record on August 28, 2014