Basal Cell Carcinoma Clinical Trial
— BOLTOfficial 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
Verified date | August 2019 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study assessed the efficacy and safety of oral treatment with two dose levels of LDE225 in patients with locally advanced or metastatic BCC.
Status | Completed |
Enrollment | 230 |
Est. completion date | June 29, 2018 |
Est. primary completion date | June 28, 2013 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
Australia | Novartis Investigative Site | Geelong | Victoria |
Australia | Novartis Investigative Site | St Leonards | New South Wales |
Belgium | Novartis Investigative Site | Bruxelles | |
Belgium | Novartis Investigative Site | Wilrijk | |
Canada | Novartis Investigative Site | Sainte-Foy | Quebec |
Canada | Novartis Investigative Site | Waterloo | Ontario |
France | Novartis Investigative Site | Lyon Cedex | |
France | Novartis Investigative Site | Marseille Cedex 05 | |
France | Novartis Investigative Site | Pierre Benite Cedex | |
France | Novartis Investigative Site | Toulouse Cedex 9 | |
France | Novartis Investigative Site | Villejuif Cedex | |
Germany | Novartis Investigative Site | Berlin | |
Germany | Novartis Investigative Site | Essen | |
Germany | Novartis Investigative Site | Freiburg | |
Germany | Novartis Investigative Site | Gera | |
Germany | Novartis Investigative Site | Hannover | |
Germany | Novartis Investigative Site | Kiel | |
Germany | Novartis Investigative Site | Mainz | |
Germany | Novartis Investigative Site | Muenchen | |
Germany | Novartis Investigative Site | Muenster | |
Germany | Novartis Investigative Site | Stade | |
Greece | Novartis Investigative Site | Athens | |
Hungary | Novartis Investigative Site | Budapest | |
Hungary | Novartis Investigative Site | Debrecen | |
Hungary | Novartis Investigative Site | Szeged | |
Italy | Novartis Investigative Site | Napoli | |
Italy | Novartis Investigative Site | Torino | TO |
Spain | Novartis Investigative Site | Barcelona | Catalunya |
Spain | Novartis Investigative Site | Madrid | |
Spain | Novartis Investigative Site | Madrid | |
Switzerland | Novartis Investigative Site | Bern | |
Switzerland | Novartis Investigative Site | Geneve | |
Switzerland | Novartis Investigative Site | Zürich | |
United Kingdom | Novartis Investigative Site | Cardiff | |
United Kingdom | Novartis Investigative Site | Glasgow | |
United Kingdom | Novartis Investigative Site | High Heaton | Newcastle Upon Tyne |
United Kingdom | Novartis Investigative Site | Leicester | |
United Kingdom | Novartis Investigative Site | London | |
United Kingdom | Novartis Investigative Site | Manchester | |
United Kingdom | Novartis Investigative Site | Yeovil | Somerset |
United States | University of Colorado School of Medicine UC | Aurora | Colorado |
United States | Dana Farber Cancer Institute DFCI - MA | Boston | Massachusetts |
United States | NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Study coordinator | Chicago | Illinois |
United States | Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology | Dallas | Texas |
United States | Texas Oncology Tex Onc 3 | Dallas | Texas |
United States | Texas Oncology Texas Onc - Amarillo | Dallas | Texas |
United States | Henry Ford Hospital Henry Ford | Detroit | Michigan |
United States | Highlands Oncology Group | Fayetteville | Arkansas |
United States | Hackensack University Medical Center Hackensack (SC) | Hackensack | New Jersey |
United States | Penn State University / Milton S. Hershey Medical Center Hershey Medical | Hershey | Pennsylvania |
United States | University of Texas MD Anderson Cancer Center MD Anderson | Houston | Texas |
United States | Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2) | Las Vegas | Nevada |
United States | University of California at Los Angeles UCLA 3 | Los Angeles | California |
United States | New York University Medical Center SC-2 | New York | New York |
United States | University of Pittsburgh Medical Center UPMC | Pittsburgh | Pennsylvania |
United States | Washington University School Of Medicine-Siteman Cancer Ctr Siteman | Saint Louis | Missouri |
United States | University of Utah / Huntsman Cancer Institute Huntsman/Univ UT | Salt Lake City | Utah |
United States | Stanford University Medical Center Stanford Univ 2 | Stanford | California |
United States | H Lee Moffitt Cancer Center and Research Institute Cutaneous Onc Dept | Tampa | Florida |
United States | Texas Oncology Cancer Care & Research Center | Waco | Texas |
United States | Washington Hospital Center Wash Hospital | Washington | District of Columbia |
United States | Texoma Cancer Center Texoma Cancer Center | Wichita Falls | Texas |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
United States, Australia, Belgium, Canada, France, Germany, Greece, Hungary, Italy, Spain, Switzerland, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | 6 months | |
Primary | 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. | 6 months | |
Secondary | 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. |
42 months | |
Secondary | 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. |
42 months | |
Secondary | 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. | 42 months | |
Secondary | 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 | 6 months | |
Secondary | 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. | 42 months | |
Secondary | 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. | 42 months | |
Secondary | 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. | 42 months | |
Secondary | 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. | 42 months | |
Secondary | 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. | 42 months | |
Secondary | 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. | 42 months | |
Secondary | 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. |
42 months | |
Secondary | 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. | 42 months | |
Secondary | 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. | 42 months | |
Secondary | 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. | 42 months | |
Secondary | 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. | Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69 | |
Secondary | 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. | 42 months |
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