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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00489086

Enrollment

Registered

2007-06-21

Start date

2004-07-31

Completion date

2012-06-30

Last updated

2020-10-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neoplastic Syndrome

Keywords

nevoid basal cell carcinoma syndrome, basal cell carcinoma of the skin

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.

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.

Interventions

DRUGtazarotene

Tazarotene is a member of the acetylenic class of retinoids.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

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. 4\. 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: i. 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. 5\. 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. 6\. 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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame
Time to Lesion Clearance	36 months
Time to Progression	36 months
Estimated Duration of Complete Response	36 months
Overall Response at Treated Lesions	36 months

Countries

United States

Participant flow

Participants by arm

Arm	Count
Tazarotene Cream This is a 36 month, multi-center, single arm, open label clinical study design	36
Total	36

Baseline characteristics

Characteristic	Tazarotene Cream
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	36 Participants
Age, Continuous	53 years STANDARD_DEVIATION 10
Region of Enrollment United States	36 participants
Sex: Female, Male Female	16 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 36
other Total, other adverse events	31 / 36
serious Total, serious adverse events	2 / 36

Outcome results

Primary

Complete Response Rate

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