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

August 13, 2019 updated by: Novartis Pharmaceuticals

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

230

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LDE225 200 mg
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.
Drug: LDE225
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 Names:
  • Sonidegib
Experimental: LDE225 800 mg
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.
Drug: LDE225
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 Names:
  • Sonidegib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
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)
Time Frame: 6 months
ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 6 months after starting LDE225 treatment.Treatment with sonidegib was considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
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)
Time Frame: 6 months
ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 6 months after starting LDE225 treatment.Treatment with sonidegib was to be considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time Frame: 42 months

Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason.

Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.

Progressive disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
42 months
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time Frame: 42 months

Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason.

Median DoR for patients with laBCC was non-estimable for both treatment arms. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
42 months
Complete Response Rate (CRR) Per Central Review (pEAS)
Time Frame: 42 months
Rate of complete response is the percentage of patients with best overall response of complete response (CR) after starting LDE225 treatment. The rate of CR was determined according to mRECIST for laBCC and RECIST 1.1 for mBCC. Patients with best overall response of 'Unknown" were treated as non responders. Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
42 months
Complete Response Rate (CRR) Per Central Review (FAS)
Time Frame: 6 months
Rate of complete response is the proportion of patients with best overall response of complete response (CR) after starting LDE225 treatment. The rate of CR will be determined according to mRECIST for laBCC and RECIST 1.1 for mBCC. Patients with best overall response of 'Unknown" will be treated as non responders
6 months
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time Frame: 42 months
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
42 months
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time Frame: 42 months
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
42 months
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time Frame: 42 months
Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
42 months
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time Frame: 42 months
Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
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)
Time Frame: 42 months
ORR is the percentage of patient's objective response (ORR) by 42 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 42 months after starting LDE225 treatment. Treatment with sonidegib was considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
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)
Time Frame: 42 months
ORR is the percentage of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 42 months after starting LDE225 treatment.Treatment with sonidegib was to be considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
42 months
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time Frame: 42 months

Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason.

Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.

Progressive disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
42 months
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time Frame: 42 months
Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
42 months
Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time Frame: 42 months
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
42 months
Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time Frame: 42 months
Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
42 months
Plasma Concentration of Sonidegib (LDE225)
Time Frame: Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
Blood PK samples were collected either by direct venipuncture or an indwelling cannula inserted in a forearm vein for the determination of trough (Cmin) plasma concentrations of sonidegib and its main circulating metabolite, LGE899, from all patients who enrolled in the study. Blood was collected in Weeks 1, 3, 5, 9 (pre-dose), and subsequently pre-dose every 4 weeks up to Week 21, and every 12 weeks thereafter up to week 69.
Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
Overall Survival (OS)
Time Frame: 42 months
OS is defined as the time from date of randomization to date of death due to any cause or the last date that a patient was known to be alive (censored observation) as of the data cut-off.
42 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 29, 2011

Primary Completion (Actual)

June 28, 2013

Study Completion (Actual)

June 29, 2018

Study Registration Dates

First Submitted

March 30, 2011

First Submitted That Met QC Criteria

March 30, 2011

First Posted (Estimate)

April 1, 2011

Study Record Updates

Last Update Posted (Actual)

August 28, 2019

Last Update Submitted That Met QC Criteria

August 13, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLDE225A2201
  • 2010-022629-14 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Access Criteria

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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