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

NCT01327053 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLDE225A22012010-022629-14
• Study Type: interventional
• Target: 230
• Locations: 12 countries
• Sites: 62

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.

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (16)

• Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)

  42 months

• Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)

  42 months

• Complete Response Rate (CRR) Per Central Review (pEAS)

  42 months

• Complete Response Rate (CRR) Per Central Review (FAS)

  6 months

• Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)

  42 months

Study Arms (2)

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.

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.

Drug: LDE225

Interventions

LDE225 DRUG

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.

Also known as: Sonidegib

LDE225 200 mg; LDE225 800 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with locally advanced BCC and metastatic BCC
• Patients with adequate bone marrow, liver, and renal function

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (62)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

University of California at Los Angeles UCLA 3

Los Angeles, California, 90095, United States

Location

Stanford University Medical Center Stanford Univ 2

Stanford, California, 94304, United States

Location

University of Colorado School of Medicine UC

Aurora, Colorado, 80045, United States

Location

Washington Hospital Center Wash Hospital

Washington D.C., District of Columbia, 20010, United States

Location

H Lee Moffitt Cancer Center and Research Institute Cutaneous Onc Dept

Tampa, Florida, 33612, United States

Location

NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Study coordinator

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute DFCI - MA

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital Henry Ford

Detroit, Michigan, 48202 2689, United States

Location

Washington University School Of Medicine-Siteman Cancer Ctr Siteman

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)

Las Vegas, Nevada, 89109, United States

Location

Hackensack University Medical Center Hackensack (SC)

Hackensack, New Jersey, 07601, United States

Location

New York University Medical Center SC-2

New York, New York, 10016, United States

Location

Penn State University / Milton S. Hershey Medical Center Hershey Medical

Hershey, Pennsylvania, 17033-085, United States

Location

University of Pittsburgh Medical Center UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology

Dallas, Texas, 75246, United States

Location

Texas Oncology Tex Onc 3

Dallas, Texas, 75246, United States

Location

Texas Oncology Texas Onc - Amarillo

Dallas, Texas, 75246, United States

Location

University of Texas MD Anderson Cancer Center MD Anderson

Houston, Texas, 77030, United States

Location

Texas Oncology Cancer Care & Research Center

Waco, Texas, 76712, United States

Location

Texoma Cancer Center Texoma Cancer Center

Wichita Falls, Texas, 76310, United States

Location

University of Utah / Huntsman Cancer Institute Huntsman/Univ UT

Salt Lake City, Utah, 84103, United States

Location

Novartis Investigative Site

St Leonards, New South Wales, 2065, Australia

Location

Novartis Investigative Site

Geelong, Victoria, 3220, Australia

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Waterloo, Ontario, N2J 1C4, Canada

Location

Novartis Investigative Site

Sainte-Foy, Quebec, G1V 4T3, Canada

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Marseille, 13885, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Gera, 07548, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Münster, 48157, Germany

Location

Novartis Investigative Site

Stade, 21682, Germany

Location

Novartis Investigative Site

Athens, 161 21, Greece

Location

Novartis Investigative Site

Budapest, H-1085, Hungary

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Szeged, H-6725, Hungary

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Bern, 3010, Switzerland

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Novartis Investigative Site

High Heaton, Newcastle Upon Tyne, NE7 7DN, United Kingdom

Location

Novartis Investigative Site

Yeovil, Somerset, BA21 4AT, United Kingdom

Location

Novartis Investigative Site

Cardiff, CF14 4XW, United Kingdom

Location

Novartis Investigative Site

Glasgow, G3 8SJ, United Kingdom

Location

Novartis Investigative Site

Leicester, LE1 5WW, United Kingdom

Location

Novartis Investigative Site

London, EC1A 7BE, United Kingdom

Location

Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 34798846 DERIVED

• 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.

  PMID: 34669179 DERIVED

• 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.

  PMID: 28846163 DERIVED

• 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.

  PMID: 25981810 DERIVED

MeSH Terms

Conditions

Carcinoma, Basal Cell; Skin Neoplasms

Interventions

sonidegib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

230 patients evaluated in the Full Analysis Set: 79 randomized to LDE225 (Sonidegib) 200mg group \& 151 randomized to LDE225 800mg group. 1 patient randomized to the 800mg group did not receive study treatment \& thus was not counted in the Safety Set.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: April 1, 2011
• Study Start: June 29, 2011
• Primary Completion: June 28, 2013
• Study Completion: June 29, 2018
• Last Updated: August 28, 2019
• Results First Posted: November 23, 2015

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

FR (5); CA (2); HU (3); AU (2); IT (2); BE (2); ES (3); CH (3); GB (7); US (22); GR (1); DE (10)