Basal Cell CarcinomaPhase 2BOLTNCT01327053
A Phase II Study of Efficacy and Safety in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma
A Phase 2 study testing LDE225 in people with Basal Cell Carcinoma, run by Novartis Pharmaceuticals at 62 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Basal Cell Carcinoma
- What is being tested?
- LDE225
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 62 sitesin 12 countries
- Study dates
- 29 Jun 2011to 29 Jun 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with locally advanced BCC and metastatic BCC
- Patients with adequate bone marrow, liver, and renal function
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
62 sites in 12 countries.
62 sites in 12 countries
United States22 sites
University of Colorado School of Medicine UC
Aurora, Colorado, 80045
Dana Farber Cancer Institute DFCI - MA
Boston, Massachusetts, 02215
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Study coordinator
Chicago, Illinois, 60611
Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology
Dallas, Texas, 75246
Texas Oncology Tex Onc 3
Dallas, Texas, 75246
Texas Oncology Texas Onc - Amarillo
Dallas, Texas, 75246
Henry Ford Hospital Henry Ford
Detroit, Michigan, 48202 2689
Highlands Oncology Group
Fayetteville, Arkansas, 72703
Hackensack University Medical Center Hackensack (SC)
Hackensack, New Jersey, 07601
Penn State University / Milton S. Hershey Medical Center Hershey Medical
Hershey, Pennsylvania, 17033-085
University of Texas MD Anderson Cancer Center MD Anderson
Houston, Texas, 77030
Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)
Las Vegas, Nevada, 89109
University of California at Los Angeles UCLA 3
Los Angeles, California, 90095
New York University Medical Center SC-2
New York, New York, 10016
University of Pittsburgh Medical Center UPMC
Pittsburgh, Pennsylvania, 15213
University of Utah / Huntsman Cancer Institute Huntsman/Univ UT
Salt Lake City, Utah, 84103
Washington University School Of Medicine-Siteman Cancer Ctr Siteman
St Louis, Missouri, 63110
Stanford University Medical Center Stanford Univ 2
Stanford, California, 94304
H Lee Moffitt Cancer Center and Research Institute Cutaneous Onc Dept
Tampa, Florida, 33612
Texas Oncology Cancer Care & Research Center
Waco, Texas, 76712
Washington Hospital Center Wash Hospital
Washington D.C., District of Columbia, 20010
Texoma Cancer Center Texoma Cancer Center
Wichita Falls, Texas, 76310
Germany10 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Gera, 07548
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
München, 81377
Novartis Investigative Site
Münster, 48157
Novartis Investigative Site
Stade, 21682
United Kingdom7 sites
Novartis Investigative Site
Cardiff, CF14 4XW
Novartis Investigative Site
Glasgow, G3 8SJ
Novartis Investigative Site
High Heaton, Newcastle Upon Tyne, NE7 7DN
Novartis Investigative Site
Leicester, LE1 5WW
Novartis Investigative Site
London, EC1A 7BE
Novartis Investigative Site
Manchester, M13 9WL
Novartis Investigative Site
Yeovil, Somerset, BA21 4AT
France5 sites
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Marseille, 13885
Novartis Investigative Site
Pierre-Bénite, 69495
Novartis Investigative Site
Toulouse, 31059
Novartis Investigative Site
Villejuif, 94805
Hungary3 sites
Novartis Investigative Site
Budapest, H-1085
Novartis Investigative Site
Debrecen, 4032
Novartis Investigative Site
Szeged, H-6725
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28046
Switzerland3 sites
Novartis Investigative Site
Bern, 3010
Novartis Investigative Site
Geneva, 1211
Novartis Investigative Site
Zurich, 8091
Australia2 sites
Novartis Investigative Site
Geelong, Victoria, 3220
Novartis Investigative Site
St Leonards, New South Wales, 2065
Belgium2 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Wilrijk, 2610
Canada2 sites
Novartis Investigative Site
Sainte-Foy, Quebec, G1V 4T3
Novartis Investigative Site
Waterloo, Ontario, N2J 1C4
Italy2 sites
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Torino, TO, 10126
About this study
Official 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
This study assessed the efficacy and safety of oral treatment with two dose levels of LDE225 in patients with locally advanced or metastatic BCC.
- Conditions
- Basal Cell Carcinoma
- Being tested
- LDE225
- Keywords
- locally advanced basal cell carcinoma, metastatic basal cell carcinoma, LDE225, sonidegib, Basel Cell Carcinoma (BCC), skin cancer, Basel Cell Carcinoma, BCC
- Medical subject headings
- Carcinoma, Basal Cell, Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDE225Drug
Also called Sonidegib
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.
| Study group | Role | What they receive |
|---|---|---|
| LDE225 200 mg | Experimental | 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. Receives: Drug: LDE225 |
| LDE225 800 mg | Experimental | 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. Receives: Drug: LDE225 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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.
Measured: 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)
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.
Measured: 6 months
Secondary outcomes (16)
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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.
Measured: 42 months
Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
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.
Measured: 42 months
Complete Response Rate (CRR) Per Central Review (pEAS)
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.
Measured: 42 months
Complete Response Rate (CRR) Per Central Review (FAS)
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
Measured: 6 months
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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.
Measured: 42 months
Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
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.
Measured: 42 months
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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.
Measured: 42 months
Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 42 months
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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.
Measured: 42 months
Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
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.
Measured: 42 months
Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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.
Measured: 42 months
Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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.
Measured: 42 months
Plasma Concentration of Sonidegib (LDE225)
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.
Measured: Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
Overall Survival (OS)
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.
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2011 (estimated)
- Study start29 Jun 2011
- Primary completion28 Jun 2013
- Study completion29 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Basal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01327053
- Sponsor's protocol ID
- CLDE225A2201
- Other IDs
- 2010-022629-14
- Acronym
- BOLT
- Status last verified
- Aug 2019
- First submitted
- 30 Mar 2011
- Last updated
- 28 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Gutzmer R, Robert C, Loquai C, Schadendorf D, Squittieri N, Arntz R, Martelli S, Dummer R. Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis. BMC Cancer. 2021 Nov 19;21(1):1244. doi: 10.1186/s12885-021-08968-1.
PubMed 34798846Lewis K, Dummer R, Farberg AS, Guminski A, Squittieri N, Migden M. Effects of Sonidegib Following Dose Reduction and Treatment Interruption in Patients with Advanced Basal Cell Carcinoma During 42-Month BOLT Trial. Dermatol Ther (Heidelb). 2021 Dec;11(6):2225-2234. doi: 10.1007/s13555-021-00619-4. Epub 2021 Oct 20.
PubMed 34669179Lear JT, Migden MR, Lewis KD, Chang ALS, Guminski A, Gutzmer R, Dirix L, Combemale P, Stratigos A, Plummer R, Castro H, Yi T, Mone M, Zhou J, Trefzer U, Kaatz M, Loquai C, Kudchadkar R, Sellami D, Dummer R. Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol. 2018 Mar;32(3):372-381. doi: 10.1111/jdv.14542. Epub 2017 Nov 6.
PubMed 28846163Migden MR, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, Herd RM, Kudchadkar R, Trefzer U, Gogov S, Pallaud C, Yi T, Mone M, Kaatz M, Loquai C, Stratigos AJ, Schulze HJ, Plummer R, Chang AL, Cornelis F, Lear JT, Sellami D, Dummer R. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015 Jun;16(6):716-28. doi: 10.1016/S1470-2045(15)70100-2. Epub 2015 May 14.
PubMed 25981810
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01327053
- Acronym / sponsor ID
- BOLT / CLDE225A2201
- Conditions
- Basal Cell Carcinoma
- Keywords
- locally advanced basal cell carcinoma, metastatic basal cell carcinoma, LDE225, sonidegib, Basel Cell Carcinoma (BCC), skin cancer, Basel Cell Carcinoma, BCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2011 (actual)
- Primary completion
- 28 Jun 2013 (actual)
- Study completion
- 29 Jun 2018 (actual)
- First posted
- 1 Apr 2011 (estimated)
- Results
- Posted 23 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LDE225 200 mg | Experimental | Drug: LDE225The 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. |
| LDE225 800 mg | Experimental | Drug: LDE225The 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with locally advanced BCC and metastatic BCC
- Patients with adequate bone marrow, liver, and renal function
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LDE225Also: SonidegibLDE225 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. | Drug | LDE225 200 mg, LDE225 800 mg |
Primary outcome
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.
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.
16 secondary outcomes
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 (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time frame: 42 months
Complete Response Rate (CRR) Per Central Review (pEAS)
Time frame: 42 months
Complete Response Rate (CRR) Per Central Review (FAS)
Time frame: 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) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time frame: 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) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time frame: 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
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
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 (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Time frame: 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
Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Time frame: 42 months
Plasma Concentration of Sonidegib (LDE225)
Time frame: Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
Overall Survival (OS)
Time frame: 42 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34798846Gutzmer R, Robert C, Loquai C, Schadendorf D, Squittieri N, Arntz R, Martelli S, Dummer R. Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis. BMC Cancer. 2021 Nov 19;21(1):1244. doi: 10.1186/s12885-021-08968-1.
- Derived from this study: PubMed 34669179Lewis K, Dummer R, Farberg AS, Guminski A, Squittieri N, Migden M. Effects of Sonidegib Following Dose Reduction and Treatment Interruption in Patients with Advanced Basal Cell Carcinoma During 42-Month BOLT Trial. Dermatol Ther (Heidelb). 2021 Dec;11(6):2225-2234. doi: 10.1007/s13555-021-00619-4. Epub 2021 Oct 20.
- Derived from this study: PubMed 28846163Lear JT, Migden MR, Lewis KD, Chang ALS, Guminski A, Gutzmer R, Dirix L, Combemale P, Stratigos A, Plummer R, Castro H, Yi T, Mone M, Zhou J, Trefzer U, Kaatz M, Loquai C, Kudchadkar R, Sellami D, Dummer R. Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol. 2018 Mar;32(3):372-381. doi: 10.1111/jdv.14542. Epub 2017 Nov 6.
- Derived from this study: PubMed 25981810Migden MR, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, Herd RM, Kudchadkar R, Trefzer U, Gogov S, Pallaud C, Yi T, Mone M, Kaatz M, Loquai C, Stratigos AJ, Schulze HJ, Plummer R, Chang AL, Cornelis F, Lear JT, Sellami D, Dummer R. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015 Jun;16(6):716-28. doi: 10.1016/S1470-2045(15)70100-2. Epub 2015 May 14.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
62 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LDE225 in people with Basal Cell Carcinoma, run by Novartis Pharmaceuticals at 62 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 62 sites in United States, Germany, United Kingdom, France, Hungary and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01327053, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.