Pilot LDE225 in Locally Advanced or Metastatic BCC + Previously Tx Non-LDE225 Smoothened Inhibitors
This study is currently recruiting participants.
Verified January 2013 by Stanford University
Information provided by (Responsible Party):
Anne Chang, Stanford University
First received: October 11, 2011
Last updated: January 28, 2013
Last verified: January 2013
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.
• 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.
- 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
Basal Cell Carcinoma
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
||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)
Primary Outcome Measures:
- Progression Free Survival (PFS) of individuals with locally advanced or metastatic BCC who have been previously treated with a non-LDE225 Smo inhibitor [ Time Frame: End of Treatment or 12 months whichever comes first ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Biomarker levels of oral LDE225 on tumor tissue biomarkers of BCC activation (Gli 1, 2, Patched 1,2 and Ki67) in individuals which are non-naïve to Smo inhibitors other than LDE225 [ Time Frame: End of treatment or 12 months whichever comes first ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||November 2013 (Final data collection date for primary outcome measure)
Active Comparator: Refractory Group
Patients previously treated with non-LDE225 Smo inhibitor who were refractory.
800-mg (4 200-mg capsules/day) capsule
Other Name: NVP-LDE225
Active Comparator: Resistance Developed Group
Patients previously treated with non-LDE225 Smo inhibitor who were initially responsive but became resistant with progressive disease.
800-mg (4 200-mg capsules/day) capsule
Other Name: NVP-LDE225
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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 ULN(upper limit of normal)
- AST and ALT <= 2.5 x ULN or <= 5 x ULN if liver metastases are present
- Plasma creatine phosphokinase (CK) < 1.5 x ULN
- Serum creatinine <= 1.5 x ULN or 24-hour clearance >= 50ml/min
- Written informed consent obtained prior to any screening procedures
- 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 LDE225.
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 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. NB: 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 LDE225.
- Patients who are receiving other anti-neoplastic therapy (e.g. chemotherapy, targeted therapy or radiotherapy) concurrently or within 2 weeks of starting treatment with LDE225.
- Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE225.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
10 Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include:
Please refer to this study by its ClinicalTrials.gov identifier: NCT01529450
|Stanford University Cancer Institute
|Stanford, California, United States, 94305 |
|Contact: Shruthi Rangaraj 650-721-7159 email@example.com |
|Principal Investigator: Anne Chang, MD |
|Principal Investigator: Anthony Oro, MD |
||Anne Chang, MD
No publications provided
||Anne Chang, Assistant Professor of Dermatology, Stanford University
History of Changes
|Other Study ID Numbers:
||SKIN0009, SU-09022011-8371, 21759
|Study First Received:
||October 11, 2011
||January 28, 2013
||United States: Food and Drug Administration
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on June 18, 2013
Carcinoma, Basal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Basal Cell