Phase II, Randomized Double-blind Study of Efficacy and Safety of Two Dose Levels of LDE225 in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma

A Phase II Study of Efficacy and Safety in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma

Sponsors

Lead sponsor: Novartis Pharmaceuticals

Source Novartis
Brief Summary

This study assessed the efficacy and safety of oral treatment with two dose levels of LDE225 in patients with locally advanced or metastatic BCC.

Overall Status Completed
Start Date June 29, 2011
Completion Date June 29, 2018
Primary Completion Date June 28, 2013
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) 6 months
Objective Response Rate (ORR) Based on Central Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) 6 months
Secondary Outcome
Measure Time Frame
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) 42 months
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) 42 months
Complete Response Rate (CRR) Per Central Review (pEAS) 42 months
Complete Response Rate (CRR) Per Central Review (FAS) 6 months
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) 42 months
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) 42 months
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) 42 months
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) 42 months
Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (for Metastatic Basal Cell Carcinoma (mBCC)) Per Primary Efficacy Analysis Set (pEAS) 42 months
Objective Response Rate (ORR) Based on Site Investigator Review According to mRECIST (for Locally Advanced Basal Cell Carcinoma (laBCC)) and RECIST 1.1 (Metastatic Basal Cell Carcinoma (mBCC)) Per Full Analysis Set (FAS) 42 months
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) 42 months
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) 42 months
Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) 42 months
Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) 42 months
Plasma Concentration of Sonidegib (LDE225) Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
Overall Survival (OS) 42 months
Enrollment 230
Condition
Intervention

Intervention type: Drug

Intervention name: LDE225

Description: LDE225 was administered orally, on a continuous once daily dosing schedule and was supplied as 200 mg hard gelatin capsules in bottles. Every 4 weeks on the day of study visit, patients received a prescription of an adequate drug supply for self-administration at home. The 800 mg dose patients received 4 capsules of LDE225 and 200 mg dose arm patients received 1 LDE225 capsule + 3 placebo capsules.

Other name: Sonidegib

Eligibility

Criteria:

Inclusion Criteria:

- Patients with locally advanced BCC and metastatic BCC

- Patients with adequate bone marrow, liver, and renal function

Exclusion Criteria:

- Patients who had had major surgery within 4 weeks of initiation of study medication

- Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract, or known malabsorption syndromes.

- Patients with concurrent medical conditions that may interfere or potentially affect the interpretation of the study.

- Patients with neuromuscular disorders or are on concurrent treatment with drugs that may cause muscle damage.

- Patients who were on concurrent therapy with other anti-neoplastic agents.

- Patients who had taken part in an experimental drug within 4 weeks of initiation of study medication.

- Pregnant or nursing (lactating) women

- Women of child bearing potential unwilling to use 2 forms of highly effective contraception throughout the study and for 3 months after the last treatment

- Fertile males not willing to use condoms throughout the study and for 3 months after the last treatment.

- Patients who were unwilling or unable to comply with the protocol.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals
Location
facility
Highlands Oncology Group | Fayetteville, Arkansas, 72703, United States
University of California at Los Angeles UCLA 3 | Los Angeles, California, 90095, United States
Stanford University Medical Center Stanford Univ 2 | Stanford, California, 94304, United States
University of Colorado School of Medicine UC | Aurora, Colorado, 80045, United States
Washington Hospital Center Wash Hospital | Washington, District of Columbia, 20010, United States
H Lee Moffitt Cancer Center and Research Institute Cutaneous Onc Dept | Tampa, Florida, 33612, United States
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Study coordinator | Chicago, Illinois, 60611, United States
Dana Farber Cancer Institute DFCI - MA | Boston, Massachusetts, 02215, United States
Henry Ford Hospital Henry Ford | Detroit, Michigan, 48202 2689, United States
Washington University School Of Medicine-Siteman Cancer Ctr Siteman | Saint Louis, Missouri, 63110, United States
Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2) | Las Vegas, Nevada, 89109, United States
Hackensack University Medical Center Hackensack (SC) | Hackensack, New Jersey, 07601, United States
New York University Medical Center SC-2 | New York, New York, 10016, United States
Penn State University / Milton S. Hershey Medical Center Hershey Medical | Hershey, Pennsylvania, 17033-085, United States
University of Pittsburgh Medical Center UPMC | Pittsburgh, Pennsylvania, 15213, United States
Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology | Dallas, Texas, 75246, United States
Texas Oncology Tex Onc 3 | Dallas, Texas, 75246, United States
Texas Oncology Texas Onc - Amarillo | Dallas, Texas, 75246, United States
University of Texas MD Anderson Cancer Center MD Anderson | Houston, Texas, 77030, United States
Texas Oncology Cancer Care & Research Center | Waco, Texas, 76712, United States
Texoma Cancer Center Texoma Cancer Center | Wichita Falls, Texas, 76310, United States
University of Utah / Huntsman Cancer Institute Huntsman/Univ UT | Salt Lake City, Utah, 84103, United States
Novartis Investigative Site | St Leonards, New South Wales, 2065, Australia
Novartis Investigative Site | Geelong, Victoria, 3220, Australia
Novartis Investigative Site | Bruxelles, 1200, Belgium
Novartis Investigative Site | Wilrijk, 2610, Belgium
Novartis Investigative Site | Waterloo, Ontario, N2J 1C4, Canada
Novartis Investigative Site | Sainte-Foy, Quebec, G1V 4T3, Canada
Novartis Investigative Site | Lyon Cedex, 69373, France
Novartis Investigative Site | Marseille Cedex 05, 13885, France
Novartis Investigative Site | Pierre Benite Cedex, 69495, France
Novartis Investigative Site | Toulouse Cedex 9, 31059, France
Novartis Investigative Site | Villejuif Cedex, 94805, France
Novartis Investigative Site | Berlin, 13353, Germany
Novartis Investigative Site | Essen, 45147, Germany
Novartis Investigative Site | Freiburg, 79106, Germany
Novartis Investigative Site | Gera, 07548, Germany
Novartis Investigative Site | Hannover, 30625, Germany
Novartis Investigative Site | Kiel, 24105, Germany
Novartis Investigative Site | Mainz, 55131, Germany
Novartis Investigative Site | Muenchen, 81377, Germany
Novartis Investigative Site | Muenster, 48157, Germany
Novartis Investigative Site | Stade, 21682, Germany
Novartis Investigative Site | Athens, 161 21, Greece
Novartis Investigative Site | Budapest, H-1085, Hungary
Novartis Investigative Site | Debrecen, 4032, Hungary
Novartis Investigative Site | Szeged, H-6725, Hungary
Novartis Investigative Site | Torino, TO, 10126, Italy
Novartis Investigative Site | Napoli, 80131, Italy
Novartis Investigative Site | Barcelona, Catalunya, 08035, Spain
Novartis Investigative Site | Madrid, 28034, Spain
Novartis Investigative Site | Madrid, 28046, Spain
Novartis Investigative Site | Bern, 3010, Switzerland
Novartis Investigative Site | Geneve, 1211, Switzerland
Novartis Investigative Site | Zürich, 8091, Switzerland
Novartis Investigative Site | High Heaton, Newcastle Upon Tyne, NE7 7DN, United Kingdom
Novartis Investigative Site | Yeovil, Somerset, BA21 4AT, United Kingdom
Novartis Investigative Site | Cardiff, CF14 4XW, United Kingdom
Novartis Investigative Site | Glasgow, G3 8SJ, United Kingdom
Novartis Investigative Site | Leicester, LE1 5WW, United Kingdom
Novartis Investigative Site | London, EC1A 7BE, United Kingdom
Novartis Investigative Site | Manchester, M13 9WL, United Kingdom
Location Countries

Australia

Belgium

Canada

France

Germany

Greece

Hungary

Italy

Spain

Switzerland

United Kingdom

United States

Verification Date

August 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: LDE225 200 mg

Arm group type: Experimental

Description: The study was double blinded and enrolled at least 50 evaluable patients in the 200 mg LDE225 arm. The efficacy and safety of LDE225 was analyzed separately in each group. Patients who met all the inclusion and none of the exclusion criteria were treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

Arm group label: LDE225 800 mg

Arm group type: Experimental

Description: The study was double blinded and enrolled at least 100 evaluable patients in the 800 mg LDE225 arm. The efficacy and safety of LDE225 was analyzed separately in each group. Patients who met all the inclusion and none of the exclusion criteria were treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

Acronym BOLT
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov