Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01327053
Recruitment Status : Completed
First Posted : April 1, 2011
Results First Posted : November 23, 2015
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Basal Cell Carcinoma Drug: LDE225 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : June 29, 2011
Actual Primary Completion Date : June 28, 2013
Actual Study Completion Date : June 29, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Sonidegib

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 Name: 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 Name: Sonidegib




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.


  2. 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.


  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.


  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01327053


Locations
Show Show 62 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01327053    
Other Study ID Numbers: CLDE225A2201
2010-022629-14 ( EudraCT Number )
First Posted: April 1, 2011    Key Record Dates
Results First Posted: November 23, 2015
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

URL: http://www.clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
locally advanced basal cell carcinoma
metastatic basal cell carcinoma
LDE225
sonidegib
Basel Cell Carcinoma (BCC)
skin cancer
Basel Cell Carcinoma
BCC
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Basal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Basal Cell