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

• Sponsor: UCSF Benioff Children's Hospital Oakland (Other)
• Overall Status: Completed
• CT.gov ID: NCT00489086
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Locations: 2
• Arm: 1
• Duration (Months): 95
• Patients Per Site: 18
• Patients Per Site Per Month: 0.2

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 phase II trial is studying topical tazarotene to see how well it works in treating patients with basal cell skin cancer and basal cell nevus syndrome on the face.

Condition or Disease	Intervention/Treatment	Phase
Neoplastic Syndrome	Drug: tazarotene	Phase 2

Detailed Description

OBJECTIVES:

• Determine whether topical tazarotene, administered over a period of 18 months as a chemopreventive agent, reduces the incidence of basal cell carcinomas (BCCs) on treated skin in patients with basal cell nevus syndrome (BCNS).

• Expand and refine chemopreventive strategies in patients with BCNS who are at high risk for the development of BCCs.

OUTLINE: This is an open-label, multicenter study.

Patients apply topical tazarotene cream to the face once daily for 18 months in the absence of unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Single Arm Open-Label Clinical Trial of Chemotherapy of BCC's With Tazarotene 0.1% in Subjects With Basal Cell Nevus Syndrome
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: Tazarotene Cream Open label	Drug: tazarotene; Tazarotene is a member of the acetylenic class of retinoids.; Other Names: tazorac

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [36 months]

   The primary endpoint used to evaluate tazarotene efficacy for BCC chemotherapy was the complete response (CR) rate, defined as the complete visible disappearance of a patient's "target" lesion during the the 18 months of tazarotene application and its failure to recur during the ensuing 18-months. We defined surgical removal of a target lesion as a treatment failure. The primary endpoint was assessed based on intention to treat analysis such that any subject who underwent the baseline evaluation and applied at least 1 dose of tazarotene was included in the analysis. Drop-outs were considered non-responders. A priori treatment success for tazarotene was defined as a CR rate of at least 50%, and treatment failure was defined as a CR rate of 25% or less.

Secondary Outcome Measures

1. Time to Lesion Clearance [36 months]

2. Time to Progression [36 months]

3. Estimated Duration of Complete Response [36 months]

4. Overall Response at Treated Lesions [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 and Research Center Oakland	Oakland	California	United States	94609
2	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: NCT00489086
• Other Study ID Numbers: CDR0000551655; R01CA109584; NCT00500643
• First Posted: Jun 21, 2007
• Last Update Posted: Oct 29, 2020
• Last Verified: Oct 1, 2020

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

Study Results

Participant Flow

Arm/Group Title	Tazarotene Cream
Arm/Group Description	This is a 36 month, multi-center, single arm, open label clinical study design
Period Title: Overall Study
STARTED	36
Completed 18 Months	23
COMPLETED	13
NOT COMPLETED	23

Baseline Characteristics

Arm/Group Title	Tazarotene Cream
Arm/Group Description	This is a 36 month, multi-center, single arm, open label clinical study design
Overall Participants	36
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	36 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (10)
Sex: Female, Male (Count of Participants)
Female	16 44.4%
Male	20 55.6%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	The primary endpoint used to evaluate tazarotene efficacy for BCC chemotherapy was the complete response (CR) rate, defined as the complete visible disappearance of a patient's "target" lesion during the the 18 months of tazarotene application and its failure to recur during the ensuing 18-months. We defined surgical removal of a target lesion as a treatment failure. The primary endpoint was assessed based on intention to treat analysis such that any subject who underwent the baseline evaluation and applied at least 1 dose of tazarotene was included in the analysis. Drop-outs were considered non-responders. A priori treatment success for tazarotene was defined as a CR rate of at least 50%, and treatment failure was defined as a CR rate of 25% or less.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

N=2 participants excluded from analysis: N=1 due to revised BCNS diagnosis and N=1 because unable to confirm administration of at least one dose of tazarotene.

Arm/Group Title	Tazarotene Cream
Arm/Group Description	This is a 36 month, multi-center, single arm, open label clinical study design
Measure Participants	34
Count of Participants [Participants]	2 5.6%

2. Secondary Outcome

Title	Time to Lesion Clearance
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

N=2 participants excluded from analysis: N=1 due to revised BCNS diagnosis and N=1 because unable to confirm administration of at least one dose of tazarotene.

Arm/Group Title	Tazarotene Cream
Arm/Group Description	This is a 36 month, multi-center, single arm, open label clinical study design
Measure Participants	34
Count of Participants [Participants]	NA NaN

3. Secondary Outcome

Title	Time to Progression
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

N=2 participants excluded from analysis: N=1 due to revised BCNS diagnosis and N=1 because unable to confirm administration of at least one dose of tazarotene.

Arm/Group Title	Tazarotene Cream
Arm/Group Description	This is a 36 month, multi-center, single arm, open label clinical study design
Measure Participants	34
Count of Participants [Participants]	NA NaN

4. Secondary Outcome

Title	Estimated Duration of Complete Response
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

N=2 participants excluded from analysis: N=1 due to revised BCNS diagnosis and N=1 because unable to confirm administration of at least one dose of tazarotene.

Arm/Group Title	Tazarotene Cream
Arm/Group Description	This is a 36 month, multi-center, single arm, open label clinical study design
Measure Participants	34
Count of Participants [Participants]	NA NaN

5. Secondary Outcome

Title	Overall Response at Treated Lesions
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

N=2 participants excluded from analysis: N=1 due to revised BCNS diagnosis and N=1 because unable to confirm administration of at least one dose of tazarotene.

Arm/Group Title	Tazarotene Cream
Arm/Group Description	This is a 36 month, multi-center, single arm, open label clinical study design
Measure Participants	34
Count of Participants [Participants]	NA NaN

Adverse Events

Time Frame	36 months
Arm/Group Title	Tazarotene Cream
Arm/Group Description	This is a 36 month, multi-center, single arm, open label clinical study design
All Cause Mortality
	Tazarotene Cream
	Affected / at Risk (%)	# Events
Total	0/36 (0%)
Serious Adverse Events
	Tazarotene Cream
	Affected / at Risk (%)	# Events
Total	2/36 (5.6%)
Ear and labyrinth disorders
cellulitis and maxillary sinusitis	1/36 (2.8%)
Renal and urinary disorders
prostate cancer diagnosis	1/36 (2.8%)
Other (Not Including Serious) Adverse Events
	Tazarotene Cream
	Affected / at Risk (%)	# Events
Total	31/36 (86.1%)
Skin and subcutaneous tissue disorders
irritation	6/36 (16.7%)
dryness	6/36 (16.7%)
inflammation	1/36 (2.8%)
itching	3/36 (8.3%)
peeling	4/36 (11.1%)
edema	1/36 (2.8%)
rash	4/36 (11.1%)
erythema	6/36 (16.7%)

Limitations/Caveats

[Not Specified]

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.