Clinical Trials /

Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas (BCC) in Gorlin Syndrome Patients

NCT02762084

Description:

Multicenter, double-blind, randomized, vehicle-controlled evaluates the efficacy and safety of patidegib gel, 2% and 4% in comparison with vehicle in subjects at least 18 years of age that meet the diagnostic criteria for basal cell nevus syndrome (BCNS). Subjects will be randomized to receive patidegib gel 4%, patidegib gel 2%, or the vehicle gel for a 26 week treatment period.

Related Conditions:
  • Basal Cell Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas (SEB) in Gorlin Syndrome Patients

Title

  • Brief Title: Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas (SEB) in Gorlin Syndrome Patients
  • Official Title: Double-Blind, Randomized, Vehicle-Controlled Proof of Concept Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas (BCC) in Gorlin Syndrome Patients
  • Clinical Trial IDs

    NCT ID: NCT02762084

    ORG ID: Pelle-926-201

    NCI ID: 2015-004274-15

    Trial Conditions

    Basal Cell Nevus Syndrome

    Trial Interventions

    Drug Synonyms Arms
    patidegib study drug patidegib gel 2%,, patidegib gel 4%,
    vehicle gel Placebo vehicle gel

    Trial Purpose

    Multicenter, double-blind, randomized, vehicle-controlled evaluates the efficacy and safety
    of patidegib gel, 2% and 4% in comparison with vehicle in subjects at least 18 years of age
    that meet the diagnostic criteria for basal cell nevus syndrome (BCNS). Subjects will be
    randomized to receive patidegib gel 4%, patidegib gel 2%, or the vehicle gel for a 26 week
    treatment period.

    Detailed Description

    This is a multicenter, double-blind, randomized, vehicle-controlled study designed to
    compare the efficacy and safety of patidegib gel, 2% and 4% in comparison with that of
    vehicle. To be eligible for the study, subjects must be at least 18 years of age and must
    meet the diagnostic criteria for basal cell nevus syndrome BCNS.

    Approximately 18 subjects who meet the study entry criteria will be randomized in a 1:1:1
    ratio to receive patidegib gel 2%, patidegib gel 4%, vehicle gel. One or two tubes of the
    assigned study drug will be dispensed to the subject at the Baseline visit. Additional tubes
    will be dispensed at subsequent visits through Week 22. The study drug will be applied
    topically to the entire face as well as to treatment-targeted surgically eligible basal cell
    carcinomas (SEBs) at other anatomical sites twice daily for 26 weeks of treatment.

    Information on reported and observed adverse events will be obtained at each visit. An
    abbreviated physical examination will be performed at Baseline, Week 14, and Week 26.

    At Baseline and Weeks 2, 6, 10, 14, 18, 22, and 26, all visible BCCs (excluding areas below
    the knees) will be identified by the Investigator, circled in ink, photographed, measured,
    and recorded on a body diagram. Treatment targeted SEBs are defined as the five SEBs on the
    face and/or other anatomical areas identified at Baseline as SEBs will be treated during the
    26 week treatment phase. If a subject has 5 eligible previously untreated facial SEBs
    (excluding tumors on nose and eyelids) these tumors will be the subject's 5 baseline
    treatment targeted SEBs and non-facial baseline SEBs will not be treated with study
    medication.

    Trial Arms

    Name Type Description Interventions
    patidegib gel 2%, Experimental patidegib gel 2%, applied topically, twice daily for 26 weeks patidegib
    patidegib gel 4%, Experimental patidegib gel 4%, applied topically, twice daily for 26 weeks patidegib
    vehicle gel Placebo Comparator vehicle gel, applied topically, twice daily for 26 weeks vehicle gel

    Eligibility Criteria

    Inclusion Criteria:

    1. The subject is from 18 to 85 years of age, inclusive.

    2. The subject must provide written informed consent prior to any study procedures.

    3. The subject must meet diagnostic criteria for BCNS including major criterion #3a plus
    one additional major criterion or major criterion #3a plus two of the minor criteria
    outlined below:

    Major Criteria:

    - More than 2 histologically confirmed BCCs or one under the age of 20 years

    - Odontogenic keratocysts of the jaw proven by histology

    - Three or more palmar and/or plantar pits

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

    - Fused, bifid, or markedly splayed ribs.

    - First degree relative with basal cell nevus syndrome

    - PTCH1 gene mutation in normal tissue

    Minor Criteria

    - Macrocephaly

    - Congenital malformations: cleft lip or palate, frontal bossing, "coarse face",
    moderate or severe hypertelorism

    - Skeletal abnormalities: sprengel deformity, marked pectus deformity, or marked
    syndactyly of the digits

    - Radiological abnormalities: bridging of the sella turcica, vertebral anomalies
    such as hemivertebrae, fusion or elongation of the vertebral bodies, modeling
    defects of the hands and feet, or flame shaped lucencies of the hands or feet

    - Ovarian fibroma

    - Medulloblastoma

    4. The subject must have a history of at least 10 BCCs in toto present at Baseline
    and/or treated within 24 months prior to screening.

    5. The subject has at Baseline a total of at least 5 previously untreated SEBs (greatest
    diameter 5 mm or greater on the face excluding the nose and periorbital skin, 9 mm or
    greater on non-facial areas excluding the skin below the knees), as documented
    clinically by the Investigator at Baseline. Untreated is define as no previous
    surgical or topical or intralesional drug treatment. Previous treatment with
    systemically administered drugs more than 6 months prior to Baseline is not
    considered previous treatment as long as there was no clinical evidence of resistance
    to oral HH (e.g., vismodegib, patidegib, and sonidegib) inhibitors. Baseline
    treatment targeted SEBs must not exceed a diameter of > 2cm. At least one of these
    tumors must be appropriate for a 2 mm punch biopsy for biomarker analysis at Baseline
    and Week 6 visits. If a subject has 5 or more facial, excluding periorbital and nasal
    skin, SEBs at Baseline, non-facial SEBs will not be treatment targeted SEBs.

    6. The subject is willing to have SEBs biopsied for biomarkers and plasma to be
    collected to measure drug levels as required in the protocol.

    7. The subject is willing to abstain from application of non-study topical prescription
    and over the counter medications to facial skin and within 5 cm of treatment targeted
    SEBs at other anatomical areas for the duration of the study except as prescribed by
    the Investigator. Moisturizers and emollients are allowable. Subjects will be
    encouraged to use sunscreen with a sunscreen protection factor (SPF 15 or higher) at
    least once daily on all exposed skin sites.

    8. Female subjects must have a negative serum pregnancy test at Screening.

    9. If the subject is a male with a female sexual partner who is of child bearing
    potential the couple is willing to use highly effective birth control (abstinence,
    oral contraceptives, barrier method with spermicide or surgical sterilization) during
    the trial and for one month after the last application of the gel.

    10. The subject is willing to contact the study center after each primary skin care
    physician (PSCP) visit to provide the study center details of the visit and any
    treatment of skin tumors.

    11. The subject is willing to forego treatment of the treatment targeted baseline SEBs
    except when the Investigator and/or primary care giver believes that delay in
    treatment potentially might compromise the health of the subject.

    Exclusion Criteria:

    1. The subject is a woman of childbearing potential. This proscription is based on the
    key role of the HH pathway in embryogenesis, the known preclinical teratogenic
    effects of systemic cyclopamine, a naturally occurring inhibitor of smoothened, and
    the unknown level of systemic exposure following topical application in humans.

    2. The subject has used topical products to the face or within 5 cm of a treatment
    targeted SEB or systemic therapies that might interfere with the evaluation of the
    study medication during the study. Specifically these include the use of:

    - Topical glucocorticoids 30 days prior to screening

    - Retinoids (e.g., etretinate, isotretinoin, tazarotene, tretinoin, adapalene)
    systemically or topically or > 5% of an alphahydroxy acid (e.g., glycolic acid,
    lactic acid) or 5-fluorouracil or imiquimod (except as topical treatment to
    discrete BCCs) systemically or topically to the skin during the six months prior
    to entry.

    - Systemic chemotherapy within one year prior to screening. (Note: field therapy
    with topically applied treatments can be done as long as they are not applied
    within 5 cm of a treatment targeted tumor).

    - Known inhibitors of the HH signaling pathway (e.g., vismodegib, patidegib, and
    sonidegib) topically or systemically within 6 months of entry into the study.

    3. The subject has a history of hypersensitivity to any of the ingredients in the study
    medication formulation.

    4. The subject is unable or unwilling to make a good faith effort to return for all
    follow-up visits and tests.

    5. The subject has uncontrolled systemic disease.

    6. The subject has clinically important history of liver disease, including viral
    hepatitis, current alcohol abuse, or cirrhosis.

    7. The subject 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 includes
    history of other skin conditions 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 patient at high
    risk from treatment complications.

    8. The subject has a history of invasive cancer within the past five years excluding
    non-melanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of
    breast, or chronic lymphocytic lymphoma (Stage 0).

    9. The subject has current, recent (within 4 weeks of Baseline visit), or planned
    participation in an experimental drug study while enrolled in this study.

    10. The subject is unwilling or unable to comply with pregnancy prevention measures.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 85 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Clinical efficacy: change from baseline in greatest diameter treatment-targeted surgically eligible basal cell carcinomas

    Molecular efficacy: change from baseline of reduction in the the hedgehog (HH) signaling pathway target gene GLI1

    Change in safety and tolerability assessment of treatment with patidegib gel

    Secondary Outcome Measures

    Clinical efficacy: change from baseline in central facial SEBs

    Change from baseline of frequency of new SEBs on the face

    Change from baseline in the proportion of non-central facial BCCs

    Change from baseline in the proportion of baseline treatment targeted SEBs

    Trial Keywords

    Gorlin Syndrome

    Basal Cell

    Nevus Syndrome

    BCNS

    nevoid basal cell carcinoma syndrome

    Basal cell carcinoma

    Hedgehog

    Surgically Eligible Basal Cell Carcinomas