Clinical Trials

Screening Inclusion Criteria:

• The participant must be at least 18 years of age at the time of informed consent.
• The participant must provide written informed consent prior to any study procedures.
• The participant must meet diagnostic criteria for Gorlin Syndrome (GS) including major criterion #3a plus 1 additional major criterion or plus 2 additional minor criteria listed below. While not required for study entry, if participant has genetic testing results available at study entry or any time during the study, the testing result will be collected.

Major Criteria

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

Minor Criteria

• Macrocephaly.
• Congenital malformations including frontal bossing, cleft lip or palate, "coarse face", moderate to severe hypertelorism.
• Skeletal abnormalities detectable clinically: Sprengel deformity, marked pectus deformity, or marked finger syndactyly.
• 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.
• Ovarian fibroma.
• Medulloblastoma.
• The participant is willing to have blood collected for safety and PK testing.
• The participant is willing to abstain from application of a non-study topical medication (prescription or over the counter) to face for the duration of the trial. 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 on the face.
• Participants of childbearing potential must agree to use a medically acceptable, highly effective form of contraception for the entire duration of the study including through the follow-up period.
• The participant is willing to forego treatment of BCCs with anything other than the study IP except when the Investigator believes that delay of treatment of a BCC potentially might
  compromise the health of the participant. During the trial, the only allowed form of BCC treatment is surgical.

Screening Exclusion Criteria:

• The participant has previously participated in a clinical trial evaluating sirolimus topical gel within the last 5 years.
• Participants with known hypersensitivity to any of the ingredients in the study medication formulation.
• Participants with current, recent (within five half-lives of the experimental drug or if half-life not known, within the past 6 months prior to Day 0), or planned participation in an experimental drug study while enrolled in this study.
• Participants who are pregnant, breastfeeding or planning to become pregnant during the study including through the follow-up period.
• Participants of childbearing potential who are unwilling or unable to comply with contraception measures.
• The participant has any condition or situation which, in the Investigator's opinion, may put the participant at significant risk, could confound the study results, including disease activity, or could interfere significantly with participation in the study.
• Participants deemed by the investigator as unwilling or unable to remain compliant with all tests and procedures, including photographs of their face, if needed, adherence to the study drug administration regimen, and other protocol-required activities.

Baseline Inclusion Criteria:

Participants are eligible to be included in the study only if all the following criteria apply at Day 0, Baseline:

• The participant must have had at least a history of 10 BCCs present on the face, scalp, ears and/or neck (clinically diagnosed and/or biopsy confirmed) within 24 months prior to Randomization/Day 0.
• Female participants of childbearing potential must have a negative urine pregnancy test to participate in the study.

Baseline Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply at Day 0, Baseline:

• The participant has > 20 clinically suspicious lesions on the face at time of randomization.
• The participant has used topical or systemic treatment that might interfere with the evaluation of the study IP.  Among these are use of the following:
  • 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate (topical); itraconazole, SUBA-itraconazole (systemic) within the 3 months prior to Day 0;
  • Hedgehog inhibitors (glasdegib, vismodegib, sonidegib, patidegib) systemically within the 6 months prior to Day 0. Topical Hedgehog inhibitors within the 3 months prior to Day 0;
  • Systemic chemotherapy of any kind within 1 year prior to Day 0;
  • Known inhibitors of the mTOR signaling pathway or systemically within 2 months prior to Day 0;
  • Photodynamic therapy (PDT) to target lesions within 3 months prior to Day 0;
  • Nicotinamide orally (500mg/2 time daily) within 3 months prior to Day 0.
• The participant has previously participated in a clinical trial evaluating an investigational product for treatment of BCCs or GS within 3 months prior to Day 0.
• Participants with an ECOG > 2 at Day 0.
• Participants previously treated for invasive cancer within the past 5 years excluding nonmelanoma skin cancer, Stage I cervical cancer, in situ ductal cell carcinoma of the breast, or chronic lymphocytic leukemia (CLL) Stage 0, at Day 0.

Eligibility last updated 5/5/22. Questions regarding updates should be directed to the study team contact.