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

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: Non-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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

rate of objective response after 6 months of treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Primary endpoint 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. The primary endpoint is based on central (radiological) review of tumor assessments as per modified RECIST (mRECIST) criteria for locally advanced basal cell carcinoma (laBCC)and RECIST 1.1 criteria for metastatic basal cell carcinoma (mBCC)

Secondary Outcome Measures:

Duration of response (DoR) as the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. [ Time Frame: Baseline, every 4 weeks up to week 17, every 8 weeks during the first year and every 12 weeks thereafter ] [ Designated as safety issue: No ]
Durtaion of response as the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. For patients who have not progressed or died as of the cut-off date, duration of response will be right-censored on the date of the last non-missing tumor assessment (prior to the start of any other anti-neoplastic therapy).
Rate of complete response in patients treated with LDE225 as determined by central review and site investigator [ Time Frame: Baseline, every 4 weeks up to week 17, every 8 weeks during the first year and every 12 weeks thereafter ] [ 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
Progression free survival in patients treated with LDE225 as determined by central review and site investigator [ Time Frame: Baseline, every 4 weeks up to week 17, every 8 weeks during the first year and every 12 weeks thereafter ] [ Designated as safety issue: No ]
Progression free survival is the time from date of 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. Progression free survival will be determined according to mRECIST for laBCC and RECIST 1.1 for mBCC
Time to tumor response in patients treated with LDE225 as determined by central review and site investigator [ Time Frame: Baseline, every 4 weeks up to week 17, every 8 weeks during the first year and every 12 weeks thereafter ] [ Designated as safety issue: No ]
Time to tumor response is the time from date of randomization until first observed confirmed response (CR or PR) according to mRECIST for laBCC and RECIST 1.1 for mBCC
Rate of objective response rate in patients treated with LDE225 as determined by central review and site investigator [ Time Frame: Baseline, every 4 weeks up to week 17, every 8 weeks during the first year and every 12 weeks thereafter ] [ Designated as safety issue: No ]
Rate of objective response (ORR) is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 6. ORR will be assessed according to RECIST 1.1 for mBCC and laBCC
Changes in QT/QTc intervals and systemic drug exposure in patients treated with LDE225 [ Time Frame: Baseline, every 4 weeks ] [ Designated as safety issue: Yes ]
Changes to QT/QTc from baseline values and newly occurring qualitative ECG abnormalities based on electrocardiograms and correlation with the PK values of LDE225
LDE225 systemic concentrations in patients treated with LDE225 [ Time Frame: Week 1, week 3, week 5, week 9, week 13 and every 12 weeks thereafter. Additional samples collected on week 17 ] [ Designated as safety issue: Yes ]
Summary by treatment of trough LDE225 plasma concentrations and additional plasma concentrations at week 17 to correlate with QT/QTc.

Enrollment:	227
Study Start Date:	June 2011
Estimated Study Completion Date:	August 2014
Estimated Primary Completion Date:	December 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 100 and 50 evaluable patients on 800 mg and 200 mg LDE225 arms respectively. 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 will be prescribed by the investigator. LDE225 will be administered orally, on a continuous once daily dosing schedule. LDE225 will be supplied as 200 mg hard gelatin capsules in bottles. Every 4 weeks on the day if study visit, patients will receive a prescription of an adequate drug supply for self-administration at home. The 800 mg dose patients will receive 4 capsules of LDE225 and 200 mg dose arm will receive 1 LDE225 capsule + 3 placebo capsules. The investigator must emphasize compliance and will instruct the patient to take LDE225 exactly as prescribed.
Experimental: LDE225 800 mg The study is double blinded and will enroll at least 100 and 50 evaluable patients on 800 mg and 200 mg LDE225 arms respectively. 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 will be prescribed by the investigator. LDE225 will be administered orally, on a continuous once daily dosing schedule. LDE225 will be supplied as 200 mg hard gelatin capsules in bottles. Every 4 weeks on the day if study visit, patients will receive a prescription of an adequate drug supply for self-administration at home. The 800 mg dose patients will receive 4 capsules of LDE225 and 200 mg dose arm will receive 1 LDE225 capsule + 3 placebo capsules. The investigator must emphasize compliance and will instruct the patient to take LDE225 exactly as prescribed.

Arms

Assigned Interventions

Experimental: LDE225 200 mg

The study is double blinded and will enroll at least 100 and 50 evaluable patients on 800 mg and 200 mg LDE225 arms respectively. 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 will be prescribed by the investigator. LDE225 will be administered orally, on a continuous once daily dosing schedule. LDE225 will be supplied as 200 mg hard gelatin capsules in bottles. Every 4 weeks on the day if study visit, patients will receive a prescription of an adequate drug supply for self-administration at home. The 800 mg dose patients will receive 4 capsules of LDE225 and 200 mg dose arm will receive 1 LDE225 capsule + 3 placebo capsules. The investigator must emphasize compliance and will instruct the patient to take LDE225 exactly as prescribed.

Experimental: LDE225 800 mg

The study is double blinded and will enroll at least 100 and 50 evaluable patients on 800 mg and 200 mg LDE225 arms respectively. 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 will be prescribed by the investigator. LDE225 will be administered orally, on a continuous once daily dosing schedule. LDE225 will be supplied as 200 mg hard gelatin capsules in bottles. Every 4 weeks on the day if study visit, patients will receive a prescription of an adequate drug supply for self-administration at home. The 800 mg dose patients will receive 4 capsules of LDE225 and 200 mg dose arm will receive 1 LDE225 capsule + 3 placebo capsules. The investigator must emphasize compliance and will instruct the patient to take LDE225 exactly as prescribed.

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

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

More Information

No publications provided

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
Last Updated:	June 3, 2013
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, Glandular and Epithelial

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Basal Cell

ClinicalTrials.gov processed this record on June 13, 2013

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