Patidegib Gel for Preventing Basal Cell Carcinoma

Recruiting at 39 trial locations

Overseen By Patient Referral Support Service (US toll-free number)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Sol-Gel Technologies, Ltd.

Must not be taking: Topical treatments, Systemic therapies

Disqualifiers: Uncontrolled systemic disease, Invasive cancer, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The aim of this clinical study is to find out how well Patidegib Gel 2% works in preventing new basal cell carcinomas (BCCs) developing on the face of adults with Gorlin syndrome, and how safe Patidegib Gel 2% is to use. People who take part will apply either Patidegib Gel 2% or a Vehicle Gel (with no active drug substance) to their face twice a day for a year (12 months). The number of new BCCs on the face will be compared between those who used Patidegib Gel 2% or Vehicle Gel after 12 months.

Do I need to stop my current medications for the trial?

The trial requires you to stop using any non-study topical medications on your face during the study, unless prescribed by the investigator. It does not specify about other medications, so you should discuss your current medications with the study team.

What data supports the effectiveness of the drug Patidegib Gel for preventing basal cell carcinoma?

The research does not provide direct evidence for Patidegib Gel, but it mentions the effectiveness of similar drugs like sonidegib, which is used to treat advanced basal cell carcinoma by inhibiting the Hedgehog signaling pathway. This suggests that drugs targeting this pathway can be effective in managing basal cell carcinoma. ^{1 2 3 4 5}

Is Patidegib Gel safe for preventing basal cell carcinoma?

There is no specific safety data available for Patidegib Gel, but similar treatments like sonidegib for advanced basal cell carcinoma have shown common mild side effects such as muscle spasms, hair loss, and taste changes. ^{1 2 4 6 7}

How is Patidegib Gel different from other drugs for basal cell carcinoma?

Patidegib Gel is unique because it is a topical treatment applied directly to the skin, unlike other drugs like sonidegib, which are taken orally. This makes it potentially more convenient and may reduce systemic side effects. ^{1 2 4 5 8}

Eligibility Criteria

This trial is for adults over 18 with Gorlin Syndrome, who have had at least 15 basal cell carcinomas (BCCs) on the face in the past two years and currently have a minimum of 10 BCCs. Participants must not use other facial skin medications during the trial.

Inclusion Criteria

I am at least 18 years old.

My cancer has a PTCH1 mutation.

I have had 15 or more basal cell carcinomas on my face in the last 2 years.

Exclusion Criteria

Subject is known to have hypersensitivity to any of the ingredients in the IP formulation

I have not used any skin treatments or other medicines that could affect the study's treatment.

I have a disease that is not currently under control.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants apply either Patidegib Gel 2% or Vehicle Gel to their face twice daily for 12 months

12 months

Regular visits for imaging and dermoscopic analysis

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Patidegib Gel 2% (Hedgehog Pathway Inhibitor)

Trial Overview The study tests if Patidegib Gel 2% can prevent new BCCs on the face of Gorlin Syndrome patients compared to a Vehicle Gel without active drug. It's applied twice daily for one year, and results are measured after this period.

Participant Groups

Group I: Patidegib Gel 2% Experimental Treatment 1 Intervention

Patidegib Gel 2% (w/w), applied topically to the face twice daily for 12 months

Group II: Vehicle Gel Placebo Group 1 Intervention

Vehicle Gel, applied topically to the face twice daily for 12 months

Who Is Running the Clinical Trial?

Sol-Gel Technologies, Ltd.

Lead Sponsor

Trials

15

Recruited

4,300+

Premier Research Group plc

Industry Sponsor

Trials

65

Recruited

74,200+

John Ratliff

Premier Research Group plc

Chief Executive Officer since 2024

MBA

Dr. Milena Kanova-Petrova

Premier Research Group plc

Chief Medical Officer since 2024

MD

Findings from Research

Sonidegib, a Hedgehog pathway inhibitor, effectively induced remission in two patients with locally advanced basal cell carcinoma (BCC) within 7 months, demonstrating its efficacy in challenging cases where surgery or radiotherapy is not an option.

Mild adverse effects such as cramps, alopecia, ageusia, and weight loss were reported, aligning with the known safety profile of sonidegib, indicating it is generally well-tolerated in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with sonidegib in patients with advanced basal cell carcinoma: case reports. Puig, S., Serra-Guillén, C., Pérez-Pastor, G., et al.[2022]

In the phase 2 BOLT trial, sonidegib demonstrated significant efficacy in treating locally advanced basal cell carcinoma (BCC), with 61% of patients achieving an objective response and a median duration of response of 26.1 months.

The most common side effects of sonidegib were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%), but most were mild (grade 1 or 2), indicating that the drug is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonidegib in the Treatment of Locally Advanced Basal Cell Carcinoma. Sanmartín, O., Llombart, B., Carretero Hernández, G., et al.[2021]

In a comparison of sonidegib and vismodegib for treating advanced basal cell carcinoma, sonidegib showed a lower overall incidence of adverse events (AEs) and a slower onset of these events, suggesting it may be a safer option for patients.

Common AEs included muscle spasms and alopecia, with sonidegib patients experiencing fewer severe side effects compared to vismodegib, although further studies are needed to confirm these findings due to the lack of direct head-to-head trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Key Clinical Adverse Events in Patients with Advanced Basal Cell Carcinoma Treated with Sonidegib or Vismodegib: A Post Hoc Analysis. Gutzmer, R., Loquai, C., Robert, C., et al.[2022]

In the Phase II BOLT study, sonidegib (200 mg daily) demonstrated a high objective response rate (ORR) of 71.2% in patients with locally advanced basal cell carcinoma (laBCC) over 42 months, indicating its efficacy as a treatment option.

The efficacy of sonidegib was maintained in patients taking select concomitant medications, with an ORR of 73.0%, suggesting that it can be safely administered alongside other treatments, except for strong cytochrome P450 3A4/5 inhibitors/inducers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant medication use does not appear to alter long-term efficacy of sonidegib for advanced basal cell carcinoma: a post hoc analysis based on the 42-month BOLT study. Lear, JT., Robert, C., Grob, JJ., et al.[2023]

In a study of 33 patients with advanced basal cell carcinoma treated with hedgehog inhibitors, vismodegib resulted in a complete response in 33% and a partial response in another 33%, while sonidegib had a higher complete response rate of 42%.

Adverse events were the most common reason for discontinuation of therapy, highlighting the need for careful management of side effects and the exploration of additional treatment options, such as immunotherapy, to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eight Years of Real-Life Experience with Smoothened Inhibitors in a Swiss Tertiary Skin Referral Center. Grossmann, LE., Ramelyte, E., Nägeli, MC., et al.[2022]

Sonidegib and vismodegib, the only approved systemic treatments for advanced basal cell carcinoma (BCC), show similar efficacy in treating the disease, as demonstrated by comparable objective response rates and complete response rates in pivotal clinical studies.

Both drugs have similar safety profiles, with common side effects including muscle spasms, hair loss, and altered taste; however, they differ in their pharmacokinetics, with sonidegib reaching peak plasma concentration faster than vismodegib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Hedgehog Inhibitors Sonidegib and Vismodegib for Treatment of Advanced Basal Cell Carcinoma. Migden, M., Farberg, AS., Dummer, R., et al.[2021]

Sonidegib is an effective treatment for advanced basal cell carcinoma (BCC), showing objective response rates of 43% for the 200 mg dose and 38% for the 800 mg dose in the BOLT clinical trials, which involved patients who could not undergo surgery or radiation.

The 200 mg dose of sonidegib resulted in fewer adverse events compared to the 800 mg dose, suggesting that lower doses may provide a better benefit-to-risk ratio for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma. Wahid, M., Jawed, A., Dar, SA., et al.[2020]

Sonidegib (LDE225) is an FDA-approved oral medication that acts as a Smoothened (SMO) antagonist, providing a new treatment option for patients with advanced basal cell carcinoma who cannot undergo surgery or radiotherapy.

The article reviews the pharmacology and pharmacokinetics of sonidegib, along with insights from the BOLT trial, highlighting its efficacy and the ongoing challenges faced with Hedgehog inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update. Chen, L., Silapunt, S., Migden, MR.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Experience with sonidegib in patients with advanced basal cell carcinoma: case reports. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Sonidegib in the Treatment of Locally Advanced Basal Cell Carcinoma. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Key Clinical Adverse Events in Patients with Advanced Basal Cell Carcinoma Treated with Sonidegib or Vismodegib: A Post Hoc Analysis. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Concomitant medication use does not appear to alter long-term efficacy of sonidegib for advanced basal cell carcinoma: a post hoc analysis based on the 42-month BOLT study. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Eight Years of Real-Life Experience with Smoothened Inhibitors in a Swiss Tertiary Skin Referral Center. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A Review of Hedgehog Inhibitors Sonidegib and Vismodegib for Treatment of Advanced Basal Cell Carcinoma. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update. [2019]