Clinical trial NCT01327053: A Phase II Study of Efficacy and Safety in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-04-01
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
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)
timeFrame: 6 months
measure: 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)
timeFrame: 6 months
Secondary outcomes:
measure: Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
timeFrame: 42 months
measure: Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
timeFrame: 42 months
measure: Complete Response Rate (CRR) Per Central Review (pEAS)
timeFrame: 42 months
measure: Complete Response Rate (CRR) Per Central Review (FAS)
timeFrame: 6 months
measure: Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
timeFrame: 42 months
measure: Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
timeFrame: 42 months
measure: Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
timeFrame: 42 months
measure: Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
timeFrame: 42 months
measure: 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)
timeFrame: 42 months
measure: 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)
timeFrame: 42 months
measure: Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
timeFrame: 42 months
measure: Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
timeFrame: 42 months
measure: Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
timeFrame: 42 months
measure: Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
timeFrame: 42 months
measure: Plasma Concentration of Sonidegib (LDE225)
timeFrame: Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
measure: Overall Survival (OS)
timeFrame: 42 months
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA 3
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center Stanford Univ 2
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine UC
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center Wash Hospital
state: District of Columbia
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute Cutaneous Onc Dept
state: Florida
city: Chicago
country: United States
facility: NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Study coordinator
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute DFCI - MA
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital Henry Ford
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School Of Medicine-Siteman Cancer Ctr Siteman
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center Hackensack (SC)
state: New Jersey
city: New York
country: United States
facility: New York University Medical Center SC-2
state: New York
city: Hershey
country: United States
facility: Penn State University / Milton S. Hershey Medical Center Hershey Medical
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Tex Onc 3
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Onc - Amarillo
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center MD Anderson
state: Texas
city: Waco
country: United States
facility: Texas Oncology Cancer Care & Research Center
state: Texas
city: Wichita Falls
country: United States
facility: Texoma Cancer Center Texoma Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Huntsman/Univ UT
state: Utah
city: St Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Geelong
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Waterloo
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Sainte-Foy
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Marseille Cedex 05
country: France
facility: Novartis Investigative Site
city: Pierre Benite Cedex
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gera
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Stade
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Geneve
country: Switzerland
facility: Novartis Investigative Site
city: Zürich
country: Switzerland
facility: Novartis Investigative Site
city: High Heaton
country: United Kingdom
facility: Novartis Investigative Site
state: Newcastle Upon Tyne
city: Yeovil
country: United Kingdom
facility: Novartis Investigative Site
state: Somerset
city: Cardiff
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Lewis 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.
citation: Lear 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.
citation: Migden 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.