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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01327053
First received: March 30, 2011
Last updated: March 14, 2016
Last verified: March 2016
  Purpose
This study will assess the efficacy and safety of oral treatment with two dose levels of LDE225 in patients with locally advanced or metastatic BCC.

Condition Intervention Phase
Basal Cell Carcinoma
Drug: LDE225
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    ORR is the proportion of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder will be 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.

  • 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 Primary Efficacy Analysis Set (pEAS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    ORR is the proportion of patient's objective response (ORR) by 6 months after starting LDE225 treatment. A responder will be 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.


Secondary Outcome Measures:
  • Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC -Per pEAS [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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 as limited numbers of progressive disease (PD) or deaths were observed as of the 28-Jun-2013 data cut-off date. Median DoR was non-estimable for patients with mBCC receiving treatment with sonidegib 200 mg.

    Duration of response was for participants with ORR.


  • Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC Per FAS [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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. Median DoR was non-estimable for patients with mBCC receiving treatment with sonidegib 200 mg.

    Duration of response was for participants with ORR.


  • Complete Response Rate (CRR) Per Central Review - Per pEAS [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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

  • Complete Response Rate (CRR) Per Central Review - Per FAS [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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


Enrollment: 229
Study Start Date: June 2011
Estimated Study Completion Date: July 2016
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDE225 200 mg
The study is double blinded and will enroll at least 50 evaluable patients in the 200 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be 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 is double blinded and will enroll at least 100 evaluable patients in the 800 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 have 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 are on concurrent therapy with other anti-neoplastic agents.
  • Patients who have 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 are unwilling or unable to comply with the protocol.

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01327053

  Show 63 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01327053     History of Changes
Other Study ID Numbers: CLDE225A2201  2010-022629-14 
Study First Received: March 30, 2011
Results First Received: August 24, 2015
Last Updated: March 14, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
locally advanced basal cell carcinoma,
metastatic basal cell carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Basal Cell
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Basal Cell
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 30, 2016