ATO: Arsenic Trioxide in Treating Patients With Basal Cell Carcinoma

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01791894
• Collaborator: The V Foundation for Cancer Research (Other)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 31
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This pilot clinical trial studies arsenic trioxide in treating patients with basal cell carcinoma. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stop them from dividing

Condition or Disease	Intervention/Treatment	Phase
Basal Cell Carcinoma of the Skin; Recurrent Skin Cancer	Drug: arsenic trioxide	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine whether administration of arsenic trioxide (ATO) to patients with basal cell carcinoma is associated with a reduction in Gli messenger ribonucleic acid (mRNA) and protein levels in tumor biopsy samples, when compared to baseline levels.

SECONDARY OBJECTIVES:

1. To determine whether there is evidence of tumor size reduction of ATO against basal cell carcinoma in humans.

OUTLINE:

Patients receive arsenic trioxide intravenously (IV) over 2 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Open-label, Biomarker Study of Arsenic Trioxide for the Treatment of Patients With Basal Cell Carcinoma
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (arsenic trioxide) Patients receive arsenic trioxide IV over 2 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: arsenic trioxide; Given IV; Other Names: Arsenic (III) Oxide Arsenic Sesquioxide Arsenous Acid Anhydride AS2O3 Trisenox

Outcome Measures

Primary Outcome Measures

1. Percent Change in Biomarker (GLI2 Protein) Levels [baseline to day 33]

Secondary Outcome Measures

1. Patients With Stable Disease Post Treatment [After 3 cycles of treatment (approx. 61 days)]

   Number of patients with stable disease post treatment by RECIST criteria

2. Patients With Progressive Disease Post Treatment by RECIST Criteria [After 3 treatment cycles (approx. 61 days)]

   Patients with a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

3. Incidence of Grade 3/4 Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [Baseline to cycle 3]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

• Basal cell carcinoma (BCC)

• Ineligible for curative locoregional treatment and have either progressed on, did not tolerate, unwilling to try or ineligible for investigational smoothened antagonist such as vismodegib (GDC 0449), XL 139 (BMS 833923), IPI- 926, LDE225 and PF-04449913

• Life expectancy estimate > 3 months

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

• 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 glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional upper limit of normal

• Creatinine within normal institutional limits

• Corrected QT interval (QTC) by 12 lead electrocardiogram (EKG) < 450 msecs

• Serum potassium within normal limits

• Magnesium within normal limits

• Calcium within normal limits

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

• Evaluable tumor and be potentially eligible for pre and post ATO tumor biopsy

• Receiving potassium wasting diuretics or amphotericin, while not excluded, must be noted to have theoretically increased arrhythmia risks with ATO

EXCLUSION CRITERIA

• Concurrent use of other Investigational agents

• Cardiac arrhythmias

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

• Pregnant or lactating

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• The V Foundation for Cancer Research

Investigators

• Principal Investigator: Jean Tang, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jean Yuh Tang, Associate Professor of Dermatology, Stanford University
• ClinicalTrials.gov Identifier: NCT01791894
• Other Study ID Numbers: IRB-26400; SKIN0015
• First Posted: Feb 15, 2013
• Last Update Posted: Jun 8, 2018
• Last Verified: Oct 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Basal Cell; Arsenic Trioxide

Study Results

Participant Flow

Recruitment Details	We will recruit from medical clinic and other physicians who treat metastatic BCC

Arm/Group Title	IV ATO
Arm/Group Description	5 subjects will be treated with arsenic trioxide at 0.3 mg/kg daily via a 2 hour intravenous infusion for 5 days every 28 days (+/- 5 days) for a total of 3 cycles.
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Arsenic Trioxide)
Arm/Group Description	arsenic trioxide IV over 2 hours on days 1-5. Courses repeat every 28 days
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	5 100%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Biomarker (GLI2 Protein) Levels
Time Frame	baseline to day 33

Outcome Measure Data

Analysis Population Description

We recruited patients with biopsy-confirmed metastatic basal cell carcinoma who were had progressed on SMO inhibitors such as vismodegib (GDC 0449), IPI- 926, LEQ506 and LDE225.

Arm/Group Title	Treatment (Arsenic Trioxide)
Arm/Group Description	Patients receive arsenic trioxide IV over 2 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. arsenic trioxide: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	5
Mean (Standard Deviation) [percentage decrease]	75 (11)

2. Secondary Outcome

Title	Patients With Stable Disease Post Treatment
Description	Number of patients with stable disease post treatment by RECIST criteria
Time Frame	After 3 cycles of treatment (approx. 61 days)

Outcome Measure Data

Analysis Population Description

4 patients completed 3 cycles of treatment

Arm/Group Title	Treatment (Arsenic Trioxide)
Arm/Group Description	Patients receive arsenic trioxide IV over 2 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. arsenic trioxide: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	4
Number [participants]	3 60%

3. Secondary Outcome

Title	Patients With Progressive Disease Post Treatment by RECIST Criteria
Description	Patients with a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	After 3 treatment cycles (approx. 61 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV ATO
Arm/Group Description	5 subjects will be treated with arsenic trioxide at 0.3 mg/kg daily via a 2 hour intravenous infusion for 5 days every 28 days (+/- 5 days) for a total of 3 cycles.
Measure Participants	4
Number [participants]	1 20%

4. Secondary Outcome

Title	Incidence of Grade 3/4 Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Time Frame	Baseline to cycle 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV ATO
Arm/Group Description	5 subjects will be treated with arsenic trioxide at 0.3 mg/kg daily via a 2 hour intravenous infusion for 5 days every 28 days (+/- 5 days) for a total of 3 cycles.
Measure Participants	5
Number [number of occurrences]	2

Adverse Events

Time Frame	13 weeks
Arm/Group Title	Treatment (Arsenic Trioxide)
Arm/Group Description	Patients receive arsenic trioxide IV over 2 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. arsenic trioxide: Given IV
All Cause Mortality
	Treatment (Arsenic Trioxide)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Arsenic Trioxide)
	Affected / at Risk (%)	# Events
Total	1/5 (20%)
Blood and lymphatic system disorders
grade 3 infection	1/5 (20%)	1
grade 4 leukopenia	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Arsenic Trioxide)
	Affected / at Risk (%)	# Events
Total	1/5 (20%)
Cardiac disorders
grade 1 asymptomatic atrial flutter	1/5 (20%)	1
Investigations
transaminitis	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.