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

Study Overview
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Brief Summary
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This pilot clinical trial studies how well arsenic trioxide and itraconazole work in treating patients with basal cell cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Itraconazole may help treat fungal infections in patients with basal cell cancer. Giving arsenic trioxide with itraconazole may work better in treating basal cell cancer.

Detailed Description
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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.

Official Title
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Oral Arsenic Trioxide and Itraconazole for the Treatment of Patients With Advanced Basal Cell Carcinoma

Conditions
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Skin Basal Cell Carcinoma

Intervention / Treatment
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* Drug: Arsenic Trioxide
* Drug: Itraconazole
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Basal cell carcinoma (BCC) Patients ineligible for curative locoregional treatment and have either progressed on, did not tolerate, unwilling to try or ineligible for investigational smoothened antagonist such as Erivedge or Odomzo 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (arsenic trioxide, itraconazole)<br>Patients receive arsenic trioxide 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. | Drug: Arsenic Trioxide<br>* Given PO<br>* Other names: White Arsenic;Drug: Itraconazole<br>* Given PO<br>* Other names: Sporanox;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gli levels | Nonparametric methods (Wilcoxon sign rank test) will be used given then the continuous outcome and small sample size. | Baseline to up to 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria | Proportion of subjects with complete response, partial response, stable disease, or disease progression by RECIST criteria. | At 3 months |