Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle Applied Once or Twice Daily to Decrease the GLI1 Biomarker in Sporadic Nodular Basal Cell Carcinomas
Condition: Basal Cell Carcinomas
MeSH terms: Carcinoma; Carcinoma, Basal Cell
Intervention: Patidegib; Vehicle gel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Gorlin Syndrome; Basal Cell Nevus Syndrome BCNS; nevoid basal cell carcinoma syndrome; Basal cell carcinoma; Hedgehog inhibitor; Surgically Eligible Basal Cell Carcinomas; High Frequency Basal Cell Carcinomas

Summary:

      This is a double-blind, dose escalating, randomized, vehicle-controlled study designed to
      compare the efficacy and safety of patidegib gel 2% and 4% applied once or twice daily in
      comparison with that of vehicle in patients with Basal Cell Carcinoma. One investigational
      center (metasite) in the United States will participate in this study. Approximately 36
      subjects who meet the study entry criteria will be enrolled into one of four sequential
      cohorts. Within each cohort subjects will be randomized in a 2:1 ratio to receive active or
      vehicle gel.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The participant is from 18 to 85 years of age, inclusive.

          2. The participant must provide electronic informed consent prior to any study
             procedures.

          3. If the participant is a woman of childbearing potential, she is willing to use two
             effective methods of birth control during the duration of the trial and for one month
             after the last application of the gel. The two forms of birth control authorized are
             defined as the use of a barrier method of contraception (condom with spermicide) in
             association with one of the following methods of birth control: bilateral tubal
             ligation; combined oral contraceptives (estrogens and progesterone) or implanted or
             injectable contraceptives with a stable dose for at least 1 month prior to Baseline;
             hormonal intra-uterine device (IUD) inserted at least 1 month prior to Baseline. This
             proscription is based on the key role of the hedgehog (HH) pathway in embryogenesis,
             the known preclinical teratogenic effects of systemic cyclopamine, a naturally
             occurring inhibitor of smoothened (SMO), and the unknown level of systemic exposure
             following topical application of patidegib in humans.

          4. If the participant is a male with a female sexual partner who is of childbearing
             potential, the couple is willing to use two effective methods of birth control during
             the duration of the trial and for one month after the last application of the gel.
             Authorized birth control methods are outlined in Inclusion Criterion #3. Any woman of
             childbearing potential applying the gel to themselves, or assisting a subject, must
             comply with the same birth control measures.

          5. One or two previously untreated basal cell carcinomas (BCCs) with the clinical
             features of a nodular BCC confirmed by a biopsy done at or prior to screening
             confirming nodular BCC. These tumors must be suitable for surgical excision. The BCCs
             prior to biopsy must be no less than 5 millimeters (mm) or greater than 15 mm in
             greatest diameter on the face and no less than 9 mm or more than 20 mm in greatest
             diameter at sites other than the face. Tumors on the nose, periorbital skin, or on or
             below the knee are excluded.

          6. The participant is willing to abstain from application of non-study topical
             prescription and over the counter medications within 5 centimeters (cm) of a
             treatment-targeted BCC 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.

          7. Female participant must have negative serum pregnancy test at Screening.

          8. The participant 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.

          9. The participant is willing to forego alternative treatment of the treatment-targeted
             baseline BCC for the duration of the trial.

        Exclusion Criteria:

          1. Participants with basal cell nevus syndrome (BCNS, Gorlin syndrome, nevoid basal cell
             carcinoma syndrome; Online Mendelian Inheritance in Man [OMIM] #109400).

          2. The participant has used topical products within 5 cm of a treatment- targeted BCC or
             systemic therapies that might interfere with the evaluation of the study medication
             during the study. Specifically, these include the use of:

               1. Topical glucocorticoids 30 days prior to screening

               2. Retinoids (such as etretinate, isotretinoin, tazarotene, tretinoin, adapalene)
                  systemically or topically, or > 5% of an alphahydroxy acid (such as glycolic
                  acid, lactic acid), photodynamic therapy (PDT), 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.

               3. 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).

               4. Known inhibitors of the HH signaling pathway (such as vismodegib, patidegib,
                  sonidegib, and itraconazole) topically or systemically within 6 months of entry
                  into the study.

          3. The participant has a history of 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 be present for
             all follow-up visits and tests.

          5. The participant is a woman who is currently nursing.

          6. The participant has any systemic disease that in the Investigator's opinion would
             interfere with the subject's ability to participate.

          7. The participant has a clinically significant history of liver disease, including viral
             hepatitis, current alcohol abuse, or cirrhosis, that in the investigator's opinion
             would interfere with the participant's ability to participate.

          8. 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 participant'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 this investigational drug or that
             might affect interpretation of the results of the study or render the participant at
             high risk from treatment complications.

          9. The participant 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 (CLL) (Stage 0).

         10. The participant is currently participating in an experimental drug study (within 4
             weeks of Baseline visit) or plans to participate in an experimental drug study while
             enrolled in this study.

         11. The participant is on a concomitant medication that is a strong CYP3A4 inhibitor.
             These include, but are not limited to: larithromycin, telithromycin, nefazodone,
             itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir,
             ritonavir, saquinavir, and tipranavir.