Clinical trial NCT03703310: Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome (Gorlin Syndrome)
Official title: A Multicenter, Randomized, Double-blind, Vehicle-controlled, Phase 3 Efficacy and Safety Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Basal Cell Nevus Syndrome
Keywords: Gorlin syndrome
Basal cell nevus syndrome BCNS
Nevoid basal cell carcinoma syndrome
Basal cell carcinoma
Hedgehog
Surgically eligible basal cell carcinomas
Patidegib
Lead sponsor: Sol-Gel Technologies, Ltd.
Sponsor class: INDUSTRY
First posted: 2018-10-11
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized 1:1 to receive Patidegib Topical Gel, 2%, or Vehicle (IP)
Primary purpose: TREATMENT

Brief summary: This is a global, multicenter, randomized, double-blind, stratified, vehicle-controlled study of the efficacy and safety of Patidegib Topical Gel, 2%, applied topically twice daily to the face of adult participants with Gorlin syndrome. Participants will be required to apply the investigational product for 12 months. The primary endpoint is a comparison between the two treatment arms of the number of new BCCs that develop over the 12 month period.

Detailed description: An open-label, extension safety and tolerability study is planned for at least 12 months duration following the end of this study. All participants who complete the Month 12 Exit Visit having demonstrated adequate compliance with application of the Investigational Product (IP) without major Protocol Deviations (PDs) during the study will be eligible for participation in the extension study.

All participants will be contacted by phone approximately 30 days following the Exit or Discontinuation Visit to determine if the participant has experienced any new adverse events (AEs)/serious AEs (SAEs) since discontinuation/completion of study treatment.

Eligibility criteria: Inclusion Criteria:

1. The participant must be age at least 18 years of age at the Screening Visit.
2. The participant must provide written informed consent prior to any study procedures.
3. The participant must meet diagnostic criteria for the basal cell nevus (Gorlin) syndrome including major criterion #3a plus 1 additional major criterion or plus 2 additional minor criteria listed below.

   Major criteria:
   1. \>2 histologically confirmed BCCs or 1 for participant under age 20.
   2. Odontogenic keratocysts of the jaw confirmed histologically.
   3. ≥3 palmar and/or plantar pits seen at the Screening Visit.
   4. Bilamellar calcification of the falx cerebri present at less than 20 years of age.
   5. Fused, bifid, or markedly splayed ribs.
   6. First degree relative with Gorlin syndrome.
   7. Patched protein 1 (PTCH1) mutation predicted to be of functional significance in normal tissue.

   Minor criteria:
   1. Macrocephaly.
   2. Congenital malformations including frontal bossing, cleft lip or palate, "coarse face", moderate to severe hypertelorism.
   3. Skeletal abnormalities detectable clinically: Sprengel deformity, marked pectus deformity, or marked finger syndactyly.
   4. Skeletal abnormalities detectable radiographically: bridging of the sella turcica; vertebral abnormalities such as hemivertebrae, fusion or elongation of the vertebral bodies; modeling defects of the hands and feet; flame shaped lucencies of the hands or feet.
   5. Ovarian fibroma.
   6. Medulloblastoma (Modification of criteria of V Kimonis et al Am J Med Genet 69: 299-308, 1997).
4. The participant must have 10 (with at least 3 on the face) clinically typical BCCs present within 24 months prior to Randomization (Baseline/Day 1). Additionally, the subject must have at least 2 BCCs with longest diameter \<5 mm present on the face prior to Randomization (Baseline/Day 1).
5. The participant is willing to have blood collected to measure circulating drug levels.
6. The participant is willing to abstain from application of a non-study topical medication (prescription or over the counter) to facial skin for the duration of the trial except as prescribed by the Investigator. Moisturizers and emollients are allowed. Participant will be encouraged to use their preferred sunscreen with a sun protector factor (SPF) of at least 30 daily on all exposed skin sites.
7. If the participant is a woman of childbearing potential (WOCBP), she must be willing to use complete abstinence from sexual intercourse and/or she and her partner must be willing to use at least 2 highly-effective forms of birth control starting prior to Baseline, through the duration of the study, and for 12 months after last application of IP.
8. If the participant is a male with a female sex partner who is a WOCBP, the participant must be willing to use condoms, even after a vasectomy, starting prior to Baseline, through the duration of the study, and for at least 8 months after the last application of IP.
9. The participant is willing for all facial BCCs to be evaluated and treatment recommendations made only by the Investigator.
10. The participant is willing to forego treatment of facial BCCs with anything other than the study IP except when the Investigator believes that delay of treatment of a facial BCC potentially might compromise the health of the subject. During the trial the only allowed form of treatment is surgical. Non-facial BCCs may be removed at the discretion of the Investigator or Primary Skin Care Physician (PSCP).

Exclusion Criteria:

1. The subject has previously participated in a clinical trial evaluating patidegib topical gel.
2. The participant has used topical treatment to the face or systemic therapies that might interfere with the evaluation of the study IP. Among these are use of the following:

   1. 5-fluorouracil, imiquimod, diclofenac, or Ingenol mebutate (except as topical treatment to discrete non-facial BCCs) systemically or topically to the skin within the 2 months prior to the Screening Visit.
   2. Systemic chemotherapy within 1 year prior to the Screening Visit.
   3. Known inhibitors of the Hedgehog signaling pathway (such as vismodegib, sonidegib, itraconazole) topically or systemically within 3 months prior to the Screening Visit.
   4. Photodynamic therapy (PDT) except to localized non-facial, individual BCCs within 2 months prior to the Screening Visit.
3. The participant is known to have a hypersensitivity to any of the ingredients in the study medication formulation.
4. The participant is unable or unwilling to make a good faith effort to return to the study site for all study visits and tests.
5. The participant has uncontrolled systemic disease.
6. The participant has been treated for invasive cancer within the past 5 years excluding non-melanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of the breast, or chronic lymphocytic leukemia (CLL) Stage 0.
7. The participant has current, recent (within five half-lives of the experimental drug or if half-life not known, within the past 6 months prior to the Screening Visit), or planned participation in an experimental drug study while enrolled in this study.
8. The participant is a WOCBP who is unwilling or unable to comply with pregnancy prevention measures.
9. The participant is pregnant or breastfeeding.
10. The participant has 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. This may include a history of other skin conditions (such as severe facial eczema) or diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the participant at high risk from treatment complications.

Primary outcomes:
measure: Number of New BCCs Per Participant
timeFrame: Month 12
Secondary outcomes:
measure: Number of New Surgically Eligible BCCs (nSEBs) Per Participant
timeFrame: Month 12
measure: Percentage of Participants Developing >=2 Facial New BCCs
timeFrame: Month 12
measure: Percentage of Participants Developing >=1 Facial New BCCs
timeFrame: Month 12
measure: Number of New BCCs Per Participant
timeFrame: Month 9
measure: Number of New BCCs Per Participant
timeFrame: Month 6
measure: Change in Advanced Basal Cell Carcinoma Index (aBCCdex) Lesion Symptom Score Scale Score
timeFrame: Month 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinical Cancer Center
state: Arizona
city: Newport Beach
country: United States
facility: Dermatology Center of Newport
state: California
city: Redwood City
country: United States
facility: Stanford University, Department of Dermatology
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Ormond Beach
country: United States
facility: Leavitt Medical Associates of Florida
state: Florida
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Carmel
country: United States
facility: Laser & Skin Surgery Center of Indiana
state: Indiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Dept of Dermatology
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota, Department of Dermatology
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Dermatology
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Murray
country: United States
facility: University of Utah Midvalley Dermatology
state: Utah
city: Brussels
country: Belgium
facility: PellePharm Investigative Site
city: Leuven
country: Belgium
facility: PellePharm Investigative Site
city: Vancouver
country: Canada
facility: Clinical Trials Unit - The Skin Care Centre
state: British Columbia
city: Toronto
country: Canada
facility: Pellepharm Investigative Site
city: Copenhagen
country: Denmark
facility: PellePharm Investigative Site
city: Bordeaux Cedex
country: France
facility: Hopital Saint-Andre - CHU Bordeaux
city: Lille Cedex
country: France
facility: CHRU de Lille - Hopital Claude HURIEZ
city: Marseille
country: France
facility: CHU La Timone
city: Nantes
country: France
facility: PellePharm Investigative Site
city: Paris
country: France
facility: Hopital Saint-Louis
city: Pierre-Bénite
country: France
facility: PellePharm Investigative Site
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin
city: Munich
country: Germany
facility: Klinik und Poliklinik fur Dermatologie und Allergologie
city: Münster
country: Germany
facility: Universitatsklinikum Münster
city: Tübingen
country: Germany
facility: Universitats Hautklinik
city: Napoli
country: Italy
facility: Ospedale Vanvitelli-University della Campania-Dermatologia Edificio 9
city: Roma
country: Italy
facility: Catholic University of the Sacred Heart
city: Rozzano
country: Italy
facility: Humanitas University Milan
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center - Dept of Dermatology
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitiario Virgen de la Macarena
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: London
country: United Kingdom
facility: Royal London Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
Study officials:
affiliation: PellePharm, Inc.
name: VP, Clinical Operations
role: STUDY_DIRECTOR
References: