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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Skin Basal Cell Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Itraconazole; Drug: Arsenic Trioxide

Detailed Description

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.

• Study Type: Interventional
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (arsenic trioxide, itraconazole); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Itraconazole; Given PO; Other Names: Sporanox; Lozanoc; Oriconazole; R 51,211; Drug: Arsenic Trioxide; Given PO; Other Names: Arsenic (III) Oxide; Arsenic Sesquioxide; Arsenous Acid Anhydride; Trisenox; Arsenous Acid; Arsenous Oxide; White Arsenic

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jean Yuh Tang
• Investigators: Principal Investigator: Jean Tang, Stanford Cancer Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: March 1, 2016
• First Submitted That Met QC Criteria: March 1, 2016
• First Posted (Estimate): March 4, 2016

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Basal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Arsenic Trioxide; Itraconazole
• Other Study ID Numbers: IRB-35488; NCI-2016-00180 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); SKIN0033 (Other Identifier: Stanford Cancer Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No