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. 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 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
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
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
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
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.
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 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.
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 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.