Arsenic Trioxide and Itraconazole in Treating Patients With Advanced Basal Cell Cancer

PRIMARY OBJECTIVES:

I. To evaluate the response of arsenic trioxide/itraconazole in patients with refractory
basal cell carcinoma.

SECONDARY OBJECTIVES:

I. To determine if this treatment is associated with a reduction in Gli messenger
ribonucleic acid (mRNA) levels in tumor and/or normal skin biopsy samples, when compared to
baseline levels.

OUTLINE:

Patients receive arsenic trioxide orally (PO) and itraconazole PO daily for 50 days,
followed by maintenance therapy consisting of 2 weeks off treatment and then 2 weeks on
treatment for up to 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

Inclusion Criteria:

- Basal cell carcinoma (BCC)

- Ineligible for curative loco regional treatment and have progressed on or did not
tolerate approved treatments of Erivedge (vismodegib, also known as GDC 0449) and
Odomzo (sonidegib, also known as erismodegib or LDE225) and have progressed on did
not tolerate or are unwilling to try other investigational agents

- Life expectancy estimate > 3 months

- Performance status Eastern Cooperative Oncology Group (ECOG) 0 to 2

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =<
2.5 X institutional upper limit of normal

- Creatinine =< 1.9 mg/dL

- Corrected QT (QTC) by 12 lead electrocardiography (EKG) < 450 msecs

- Serum potassium, magnesium and calcium levels which fall within normal limits or
levels outside the normal range determined not to be clinically significant by the
principal investigator (PI)

- Serum prothrombin time, international normalized ratio (INR) and partial
thromboplastin times which fall within normal limits or levels outside the normal
range determined not to be clinically significant by the PI

- Ability to understand and the willingness to sign a written informed consent document

- Females and males of reproductive potential must use effective contraception during
and after treatment for 6 months

Exclusion Criteria:

- Concurrent use of other investigational agents

- Cardiac arrhythmias

- Receiving potassium wasting diuretics or amphotericin must be noted to have
theoretically increased arrhythmia risks with arsenic trioxide (potassium wasting
diuretics or amphotericin are not excluded)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, liver disease, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, recurrent seizure history or psychiatric illness/social
situations that would limit compliance with treatment requirements

- Currently taking systemic medications that would affect BCC tumors (oral retinoids)
or metabolism of itraconazole (anti convulsants and corticosteroids); itraconazole
should not be taken with cisapride (Propulsid), dofetilide (Tikosyn), oral midazolam
(Versed), nisoldipine (Sular), pimozide (Orap), quinidine (Quinaglute), triazolam
(Halcion), or levomethadyl (Orlaam), lovastatin (Mevacor), simvastatin (Zocor), or an
ergot medication such as dihydroergotamine (Migranal), ergometrine or ergonovine
(Ergotrate Maleate), ergotamine (Ergomar), or methylergometrine or methylergonovine
(Methergine)

- History or current evidence of malabsorption or liver disease that would impair the
absorption of itraconazole

- History or current evidence of hyperthyroidism that would increase metabolism of
itraconazole

- Immunosuppressed patients (cancer, autoimmune disease) or patients taking
immunosuppressive drugs

- Pregnant or breastfeeding