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Pilot LDE225 in Locally Advanced or Metastatic BCC + Previously Tx Non-LDE225 Smoothened Inhibitors
Trial ID: NCT01529450
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
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)
1. Age 18 years or older.
2. Histologically documented diagnosis of basal cell carcinoma deemed to be locally
advanced or metastatic who have previously received a non-LDE225 Smo inhibitor.
3. World Health Organization (WHO) performance status <= 2
4. 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.
5. 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
- Plasma creatine phosphokinase (CK) < 1.5 x ULN
- Serum creatinine <= 1.5 x ULN or 24-hour clearance >= 50ml/min
6. Written informed consent obtained prior to any screening procedures
1. Patients who have had major surgery within 4 weeks of initiation of study medication.
2. 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.
3. 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.
4. Patients who have previously been treated with systemic LDE225.
5. 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.
6. Patients who have taken part in an experimental drug study within 4 weeks of
initiating treatment with LDE225.
7. Patients who are receiving other anti-neoplastic therapy (e.g. chemotherapy, targeted
therapy or radiotherapy) concurrently or within 2 weeks of starting treatment with
8. Patients who are receiving treatment with medications known to be moderate and strong
inhibitors or inducers of cytochrome (CYP)3A4/5 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.
9. 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 human chorionic gonadotropin (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:
- Diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge
or spermicide. Hormonal contraceptives include any marketed contraceptive agent that
includes an estrogen and/or a progestational agent.
- Reliable contraception should be maintained throughout the study and for 3 months
after study drug discontinuation.
11 Patients unwilling or unable to comply with the protocol.
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