Topical Tazarotene in Treating Patients With Basal Cell Skin Cancer and Basal Cell Nevus Syndrome on the Chest and Back

• Sponsor: UCSF Benioff Children's Hospital Oakland (Other)
• Overall Status: Completed
• CT.gov ID: NCT00783965
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 34
• Locations: 3
• Arms: 2
• Duration (Months): 114
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as tazarotene, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This randomized phase II trial is comparing two different schedules of topical tazarotene and topical placebo to see how well they work in treating patients with basal cell skin cancer and basal cell nevus syndrome on the chest.

Condition or Disease	Intervention/Treatment	Phase
Skin Carcinoma	Drug: tazarotene; Other: placebo	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To expand and refine chemopreventive strategies in individuals with basal cell nevus syndrome (BCNS) on the chest and back, who are at high risk for the development of basal cell carcinomas (BCCs).

• To determine whether tazarotene 0.1% cream applied to the chest for two years will reduce the numbers of basal cell carcinomas (BCCs) observed, as compared to the number expected, based on changes in BCC numbers observed during months 0-12.

Secondary

• To compare the difference in total BCC burden (measured as the total lesion surface area) between chest and back over various time points and aggregated intervals of interest.

• To determine whether there are any detectable wash-in or wash-out periods for the tazarotene effects.

• Explore the use of a random effects model for longitudinal analysis of total lesions over time.

OUTLINE: This is a multicenter study. Patients are randomized into 1 of 2 arms.

• Arm I: Patients apply 0.1% tazarotene cream on months 0-12 and vehicle (placebo) on months 13-36 once daily to the chest in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients apply vehicle (placebo) on months 0-12 and 0.1% tazarotene cream on months 13-36 once daily to the chest in the absence of disease progression or unacceptable toxicity.

Treated chest and untreated back is evaluated at 3 month intervals for 36 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized, Double-Blind, Vehicle-Controlled, Crossover Clinical Trial of Tazarotene 0.1% and Vehicle Cream Each Applied Once-Daily for 12 or 24 Months in Subjects With Basal Cell Nevus Syndrome
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients apply 0.1% tazarotene cream on months 0-12 and vehicle (placebo) on months 13-36 once daily to the chest.	Drug: tazarotene; Applied to the skin; Other Names: tazorac ; Other: placebo; Applied to the skin; Other Names: vehicle
Experimental: Arm II Patients apply, vehicle (placebo) on months 0-12 and 0.1% tazarotene cream on months 13-36 once daily to the chest.	Drug: tazarotene; Applied to the skin; Other Names: tazorac ; Other: placebo; Applied to the skin; Other Names: vehicle

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Reduction in the Observed Numbers of Basal Cell Carcinomas ≥ 9 mm² in Diameter [Baseline and 36 months]

2. Parameters of Safety: Number of Participants With Adverse Events According to NCI CTCAE v3.0 [Baseline and 36 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

List of Inclusion Criteria:

1. Study subjects must have at least one basal cell carcinoma ≥ 3mm in diameter (target lesion) on any area of the skin except the face, chest, and back (and not impinging on vital sites) diagnosed clinically by a Study Investigator at the baseline visit.

2. Study subjects must meet diagnostic criteria for basal cell nevus syndrome including major criterion #1 plus one additional major criterion or two of the minor criteria outlined in Table I. A first degree relative would satisfy BCNS diagnostic criteria with any two major criteria or any single major plus two minor criteria.

Table I. BCNS Diagnostic Criteria

Major criteria

1. More than 2 BCCs or one under the age of 20 years

2. Odontogenic keratocysts of the jaw proven by histology

3. Three or more palmar and/or plantar pits

4. Bilamellar calcification of the falx cerebri (if less than 20 years old)

5. Fused, bifid, or markedly splayed ribs.

6. First degree relative with basal cell nevus syndrome (BCNS)

7. PTCH1 gene mutation in normal tissue*

Minor criteria

1. Macrocephaly determined after adjustment for height

2. Congenital malformations: cleft lip or palate, frontal bossing, "coarse face."

3. Skeletal abnormalities: Sprengel deformity, marked pectus deformity

4. Radiological abnormalities: bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies.

5. Ovarian fibroma

6. Medulloblastoma

3.The subject is from 18-75 years of age, inclusive.

1. If the subject is female and of child-bearing potential (women are considered not of childbearing potential if they are at least 2 years post-menopausal and/or surgically sterile), she:

1. has been using adequate contraception (abstinence, IUD, birth control pills, or spermicidal gel with diaphragm or condom) since her last menses and will use adequate contraception during the study, and ii. is not lactating, and iii. has documented one negative serum pregnancy test within 14 days prior to study entry.

1. The subject is willing to abstain from application of non-study topical medications to the skin of the face for the duration of the study, including prescription and over the counter preparations.

2. The subject is willing not to have targeted BCCs treated by their PSCP unless the BCCs are documented by Study Investigators, preferably on two separate visits, except when the PSCP believes that delay in treatment potentially might compromise the health of the subject.

List of Exclusion Criteria:

1. The subject has used topical or systemic therapies that might interfere with the evaluation of the study medication during the study.

2. The subject has a history of hypersensitivity to any of the ingredients in the study medication formulations.

3. The subject is unable to return for follow-up tests.

4. The subject has uncontrolled systemic disease, including known HIV positive patients.

5. The subject has a history of other skin conditions or significant illness that would interfere with evaluation of the study medication.

6. Any condition or situation which in the Investigator's opinion may put the subject at significant risk, could confound the study results, or could interfere significantly with the subject's participation in the study.

7. The subject has a history of invasive cancer within the past five years excluding non-melanoma skin cancer, Stage I cervical cancer, or CLL Stage 0.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Oakland Research Institute	Oakland	California	United States	94609-1693
2	Children's Hospital Oakland Research Institiute	Oakland	California	United States	94609
3	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• UCSF Benioff Children's Hospital Oakland
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ervin Epstein, MD, UCSF Benioff Children's Hospital Oakland
• Principal Investigator: David R. Bickers, MD, Herbert Irving Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UCSF Benioff Children's Hospital Oakland
• ClinicalTrials.gov Identifier: NCT00783965
• Other Study ID Numbers: CDR0000618240; 5R01CA109584-05; U19CA081888
• First Posted: Nov 2, 2008
• Last Update Posted: Feb 11, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by UCSF Benioff Children's Hospital Oakland: nevoid basal cell carcinoma syndrome; basal cell carcinoma of the skin
• Additional relevant MeSH terms: Carcinoma; Basal Cell Nevus Syndrome; Tazarotene

Study Results

Participant Flow

Arm/Group Title	Arm I	Arm II
Arm/Group Description	0.1% tazarotene cream first, then placebo	Vehicle (placebo) first, then 0.1% tazarotene cream
Period Title: First Intervention (12 Months)
STARTED	5	29
COMPLETED	2	25
NOT COMPLETED	3	4
Period Title: First Intervention (12 Months)
STARTED	2	25
COMPLETED	2	16
NOT COMPLETED	0	9

Baseline Characteristics

Arm/Group Title	Arm I	Arm II	Total
Arm/Group Description	Patients apply 0.1% tazarotene cream on months 0-12 and vehicle (placebo) on months 13-36 once daily to the chest. placebo : Applied to the skin tazarotene : Applied to the skin	Patients apply, vehicle (placebo) on months 0-12 and 0.1% tazarotene cream on months 13-36 once daily to the chest. placebo : Applied to the skin tazarotene : Applied to the skin	Total of all reporting groups
Overall Participants	5	29	34
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	29 100%	34 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (7)	51 (13)	53 (10)
Sex: Female, Male (Count of Participants)
Female	3 60%	14 48.3%	17 50%
Male	2 40%	15 51.7%	17 50%
Region of Enrollment (participants) [Number]
United States	5 100%	29 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Reduction in the Observed Numbers of Basal Cell Carcinomas ≥ 9 mm² in Diameter
Time Frame	Baseline and 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients apply 0.1% tazarotene cream on months 0-12 and vehicle (placebo) on months 13-36 once daily to the chest. placebo : Applied to the skin tazarotene : Applied to the skin	Patients apply, vehicle (placebo) on months 0-12 and 0.1% tazarotene cream on months 13-36 once daily to the chest. placebo : Applied to the skin tazarotene : Applied to the skin
Measure Participants	5	29
Number [participants]	5 100%	29 100%

2. Primary Outcome

Title	Parameters of Safety: Number of Participants With Adverse Events According to NCI CTCAE v3.0
Time Frame	Baseline and 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients apply 0.1% tazarotene cream on months 0-12 and vehicle (placebo) on months 13-36 once daily to the chest. placebo : Applied to the skin tazarotene : Applied to the skin	Patients apply, vehicle (placebo) on months 0-12 and 0.1% tazarotene cream on months 13-36 once daily to the chest. placebo : Applied to the skin tazarotene : Applied to the skin
Measure Participants	5	29
Number [participants]	5 100%	29 100%

Adverse Events

Arm/Group Title	Arm I		Arm II
Arm/Group Description	Patients apply 0.1% tazarotene cream on months 0-12 and vehicle (placebo) on months 13-36 once daily to the chest. placebo : Applied to the skin tazarotene : Applied to the skin		Patients apply, vehicle (placebo) on months 0-12 and 0.1% tazarotene cream on months 13-36 once daily to the chest. placebo : Applied to the skin tazarotene : Applied to the skin
All Cause Mortality
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		2/29 (6.9%)
Ear and labyrinth disorders
cellulitis and maxillary sinusitis	0/5 (0%)		1/29 (3.4%)
Renal and urinary disorders
prostate cancer diagnosis	0/5 (0%)		1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		26/29 (89.7%)
Skin and subcutaneous tissue disorders
Dryness	0/5 (0%)		6/29 (20.7%)
Inflammation	1/5 (20%)		0/29 (0%)
Itching	0/5 (0%)		3/29 (10.3%)
Irritation	2/5 (40%)		4/29 (13.8%)
Peeling	0/5 (0%)		4/29 (13.8%)
Edema	0/5 (0%)		1/29 (3.4%)
Rash	0/5 (0%)		4/29 (13.8%)
Erythema	2/5 (40%)		4/29 (13.8%)

Limitations/Caveats

Non-compliance and large drop-out rates leading to small numbers of data analyzed.

More Information

Certain Agreements

All Principal Investigators ARE 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.