Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01327053
Registration number
NCT01327053
Ethics application status
Date submitted
30/03/2011
Date registered
1/04/2011
Date last updated
28/08/2019
Titles & IDs
Public title
A Phase II Study of Efficacy and Safety in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma
Query!
Scientific title
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
Query!
Secondary ID [1]
0
0
2010-022629-14
Query!
Secondary ID [2]
0
0
CLDE225A2201
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
BOLT
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Basal Cell Carcinoma
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Non melanoma skin cancer
Query!
Cancer
0
0
0
0
Query!
Kidney
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - LDE225
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.
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.
Treatment: Drugs: 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.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
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)
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
6 months
Query!
Primary outcome [2]
0
0
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)
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
6 months
Query!
Secondary outcome [1]
0
0
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
42 months
Query!
Secondary outcome [2]
0
0
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
42 months
Query!
Secondary outcome [3]
0
0
Complete Response Rate (CRR) Per Central Review (pEAS)
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
42 months
Query!
Secondary outcome [4]
0
0
Complete Response Rate (CRR) Per Central Review (FAS)
Query!
Assessment method [4]
0
0
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
Query!
Timepoint [4]
0
0
6 months
Query!
Secondary outcome [5]
0
0
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
42 months
Query!
Secondary outcome [6]
0
0
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
42 months
Query!
Secondary outcome [7]
0
0
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Query!
Assessment method [7]
0
0
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.
Query!
Timepoint [7]
0
0
42 months
Query!
Secondary outcome [8]
0
0
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Query!
Assessment method [8]
0
0
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.
Query!
Timepoint [8]
0
0
42 months
Query!
Secondary outcome [9]
0
0
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)
Query!
Assessment method [9]
0
0
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.
Query!
Timepoint [9]
0
0
42 months
Query!
Secondary outcome [10]
0
0
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)
Query!
Assessment method [10]
0
0
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.
Query!
Timepoint [10]
0
0
42 months
Query!
Secondary outcome [11]
0
0
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Query!
Assessment method [11]
0
0
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.
Query!
Timepoint [11]
0
0
42 months
Query!
Secondary outcome [12]
0
0
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Query!
Assessment method [12]
0
0
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.
Query!
Timepoint [12]
0
0
42 months
Query!
Secondary outcome [13]
0
0
Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Query!
Assessment method [13]
0
0
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.
Query!
Timepoint [13]
0
0
42 months
Query!
Secondary outcome [14]
0
0
Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Query!
Assessment method [14]
0
0
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.
Query!
Timepoint [14]
0
0
42 months
Query!
Secondary outcome [15]
0
0
Plasma Concentration of Sonidegib (LDE225)
Query!
Assessment method [15]
0
0
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.
Query!
Timepoint [15]
0
0
Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
Query!
Secondary outcome [16]
0
0
Overall Survival (OS)
Query!
Assessment method [16]
0
0
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.
Query!
Timepoint [16]
0
0
42 months
Query!
Eligibility
Key inclusion criteria
- Patients with locally advanced BCC and metastatic BCC
- Patients with adequate bone marrow, liver, and renal function
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key 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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
29/06/2011
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
29/06/2018
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
230
Query!
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - St Leonards
Query!
Recruitment hospital [2]
0
0
Novartis Investigative Site - Geelong
Query!
Recruitment postcode(s) [1]
0
0
2065 - St Leonards
Query!
Recruitment postcode(s) [2]
0
0
3220 - Geelong
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Arkansas
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Colorado
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
District of Columbia
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Florida
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Illinois
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Massachusetts
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Michigan
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Missouri
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Nevada
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
New Jersey
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
New York
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Pennsylvania
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Texas
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
Utah
Query!
Country [16]
0
0
Belgium
Query!
State/province [16]
0
0
Bruxelles
Query!
Country [17]
0
0
Belgium
Query!
State/province [17]
0
0
Wilrijk
Query!
Country [18]
0
0
Canada
Query!
State/province [18]
0
0
Ontario
Query!
Country [19]
0
0
Canada
Query!
State/province [19]
0
0
Quebec
Query!
Country [20]
0
0
France
Query!
State/province [20]
0
0
Lyon Cedex
Query!
Country [21]
0
0
France
Query!
State/province [21]
0
0
Marseille Cedex 05
Query!
Country [22]
0
0
France
Query!
State/province [22]
0
0
Pierre Benite Cedex
Query!
Country [23]
0
0
France
Query!
State/province [23]
0
0
Toulouse Cedex 9
Query!
Country [24]
0
0
France
Query!
State/province [24]
0
0
Villejuif Cedex
Query!
Country [25]
0
0
Germany
Query!
State/province [25]
0
0
Berlin
Query!
Country [26]
0
0
Germany
Query!
State/province [26]
0
0
Essen
Query!
Country [27]
0
0
Germany
Query!
State/province [27]
0
0
Freiburg
Query!
Country [28]
0
0
Germany
Query!
State/province [28]
0
0
Gera
Query!
Country [29]
0
0
Germany
Query!
State/province [29]
0
0
Hannover
Query!
Country [30]
0
0
Germany
Query!
State/province [30]
0
0
Kiel
Query!
Country [31]
0
0
Germany
Query!
State/province [31]
0
0
Mainz
Query!
Country [32]
0
0
Germany
Query!
State/province [32]
0
0
Muenchen
Query!
Country [33]
0
0
Germany
Query!
State/province [33]
0
0
Muenster
Query!
Country [34]
0
0
Germany
Query!
State/province [34]
0
0
Stade
Query!
Country [35]
0
0
Greece
Query!
State/province [35]
0
0
Athens
Query!
Country [36]
0
0
Hungary
Query!
State/province [36]
0
0
Budapest
Query!
Country [37]
0
0
Hungary
Query!
State/province [37]
0
0
Debrecen
Query!
Country [38]
0
0
Hungary
Query!
State/province [38]
0
0
Szeged
Query!
Country [39]
0
0
Italy
Query!
State/province [39]
0
0
TO
Query!
Country [40]
0
0
Italy
Query!
State/province [40]
0
0
Napoli
Query!
Country [41]
0
0
Spain
Query!
State/province [41]
0
0
Catalunya
Query!
Country [42]
0
0
Spain
Query!
State/province [42]
0
0
Madrid
Query!
Country [43]
0
0
Switzerland
Query!
State/province [43]
0
0
Bern
Query!
Country [44]
0
0
Switzerland
Query!
State/province [44]
0
0
Geneve
Query!
Country [45]
0
0
Switzerland
Query!
State/province [45]
0
0
Zürich
Query!
Country [46]
0
0
United Kingdom
Query!
State/province [46]
0
0
Newcastle Upon Tyne
Query!
Country [47]
0
0
United Kingdom
Query!
State/province [47]
0
0
Somerset
Query!
Country [48]
0
0
United Kingdom
Query!
State/province [48]
0
0
Cardiff
Query!
Country [49]
0
0
United Kingdom
Query!
State/province [49]
0
0
Glasgow
Query!
Country [50]
0
0
United Kingdom
Query!
State/province [50]
0
0
Leicester
Query!
Country [51]
0
0
United Kingdom
Query!
State/province [51]
0
0
London
Query!
Country [52]
0
0
United Kingdom
Query!
State/province [52]
0
0
Manchester
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01327053
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Novartis Pharmaceuticals
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01327053
Download to PDF