A Pilot Open-Label Study to Examine the Safety and Efficacy of Oral LDE225 in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma Who Have Been Previously Treated With Non-LDE225 Smoothened Inhibitor(s)
Overview
- Phase
- N/A
- Intervention
- LDE225
- Conditions
- Basal Cell Carcinoma
- Sponsor
- Anne Chang
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS) of All Participants
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a prospective single-center, open label, pilot study to investigate the safety and efficacy of LDE225 in patients with locally advanced or metastatic basal cell carcinoma.
Primary Objectives:
• To explore the effects of oral LDE225 on the Progression Free Survival (PFS) of individuals with locally advanced or metastatic BCC who have been previously treated with a non-LDE225 Smo inhibitor.
Secondary Objectives:
- To evaluate the effect of oral LDE225 on tumor tissue biomarkers of BCC activation (Gii 1, 2, Patched 1,2 and Ki67) in individuals which are non-na"ive to Smo inhibitors other than LDE225, at baseline and at end-of-treatment
- To describe adverse effects of oral LDE225 in individuals with a history of non-LDE225 Smo inhibitor usage
- To assess the overall survival rates of individuals with locally advanced BCC or metastatic BCC who have previously taken a non-LDE225 Smo inhibitor after treatment with LDE225
Detailed Description
This is a prospective single-center, open label, pilot study to investigate the safety and efficacy of LDE225 in patients with locally advanced or metastatic basal cell carcinoma. Primary Objectives: • To explore the effects of oral LDE225 on the Progression Free Survival (PFS) of individuals with locally advanced or metastatic BCC who have been previously treated with a non-LDE225 Smo inhibitor. Secondary Objectives: * To evaluate the effect of oral LDE225 on tumor tissue biomarkers of BCC activation (e.g. Gli and Ki67) in individuals which are non-naive to Smo inhibitors other than LDE225, at baseline and at end-of-treatment * To describe adverse effects of oral LDE225 in individuals with a history of non-LDE225 Smo inhibitor usage
Investigators
Anne Chang
Assistant Professor of Dermatology
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Age 18 years or older.
- •Histologically documented diagnosis of basal cell carcinoma deemed to be locally advanced or metastatic who have previously received a non-LDE225 Smo inhibitor.
- •World Health Organization (WHO) performance status \<= 2
- •At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors), or other disease specific response assessment criteria, as appropriate. State age restriction and/or gender/race-ethnic restrictions.
- •Patients with adequate bone marrow, liver and renal function, as specified below:
- •Absolute Neutrophil Count (ANC) \>= 1.5 x 10\^9/L
- •Hemoglobin (Hgb) \>= 9 g/dL
- •Platelets \>= 80 x 10\^9/L
- •Serum total bilirubin \<= 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 2.5 x ULN or \<= 5 x ULN if liver metastases are present
Exclusion Criteria
- •Patients who have had major surgery within 4 weeks of initiation of study medication.
- •Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data.
- •State restrictions regarding use of other Investigational Agents.
- •Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes.
- •State exclusion requirements due to co-morbid disease or incurrent illness, as needed.
- •Patients who have previously been treated with systemic LDE
- •Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment. If it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution.
- •b) Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment. Note: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on LDE225 treatment.
- •Patients who have taken part in an experimental drug study within 4 weeks of initiating treatment with LDE
- •Patients who are receiving other anti-neoplastic therapy (e.g. chemotherapy, targeted therapy or radiotherapy) concurrently or within 2 weeks of starting treatment with LDE
Arms & Interventions
Refractory Group
Patients previously treated with non-LDE225 Smo inhibitor who were refractory.
Intervention: LDE225
Resistance Developed Group
Patients previously treated with non-LDE225 Smo inhibitor who were initially responsive but became resistant with progressive disease.
Intervention: LDE225
Outcomes
Primary Outcomes
Progression Free Survival (PFS) of All Participants
Time Frame: End of treatment or at time of disease progression (up to 58 weeks)
Secondary Outcomes
- Molecular Markers Associated With Clinical Response(Assessed on day 1)