Vismodegib for Basal Cell Carcinoma

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Statins, St. John's Wort

Disqualifiers: Pregnancy, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

34 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare how well tolerated and effective four different dosing schedules (two personalized, intermittent dosing schedules as compared to a fixed intermittent and continuous dosing regimen) work in people with advanced basal cell carcinoma.

Will I have to stop taking my current medications?

The trial requires that you do not take statins or St. John's Wort while participating. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Vismodegib for treating basal cell carcinoma?

Vismodegib has been shown to be effective in treating advanced basal cell carcinoma, with an overall response rate of 30.3% in patients with metastatic BCC and 42.9% in those with locally advanced BCC. The drug works by inhibiting the hedgehog pathway, which is involved in the development of this type of skin cancer. ^{1 2 3 4 5}

Is Vismodegib safe for humans?

Vismodegib has been shown to cause side effects like muscle spasms, hair loss, taste changes, weight loss, fatigue, nausea, and more. It is also known to be a teratogen, meaning it can cause birth defects, so it should not be used during pregnancy. ^{1 2 3 5 6}

How is the drug Vismodegib unique in treating basal cell carcinoma?

Vismodegib is unique because it is the first drug to inhibit the Hedgehog pathway, which is crucial in the development of basal cell carcinoma. It is specifically used for cases that are advanced and cannot be treated with surgery or radiation. ^{1 3 4 5 7}

Research Team

Zeynep Eroglu

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

Adults with advanced basal cell carcinoma can join this trial. They must be able to measure their tumor, have not used hedgehog inhibitors in the last 6 months, and have good liver, kidney, and bone marrow function. Pregnant or nursing women cannot participate; men and women must use contraception.

Inclusion Criteria

My liver, kidneys, and bone marrow are functioning well.

I have had treatments for basal cell carcinoma, including hedgehog inhibitors over 6 months ago.

Must have ability to comprehend and the willingness to sign written informed consent for study participation.

Exclusion Criteria

Inability or unwillingness to swallow capsules.

I am not pregnant, do not plan to become pregnant, and am not nursing.

Any known allergy, hypersensitivity or severe reaction to vismodegib or any of the ingredients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vismodegib with different dosing schedules: continuous, fixed intermittent, or personalized intermittent based on TGI model or adaptive model.

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Vismodegib

Trial Overview The study is testing four different dosing schedules of Vismodegib on patients with advanced basal cell carcinoma: two personalized intermittent doses compared to a fixed intermittent dose and a continuous regimen.

Participant Groups

Group I: Arm D: Personalized Intermittent Vismodegib (TGI model) Experimental Treatment 1 Intervention

Participants will start with an 8-week run in period with vismodegib 150 mg dose by mouth daily. Participants will take vismodegib for the first 8 weeks, then start personalized dosing based on TGI model.

Group II: Arm C: Personalized Intermittent Vismodegib (Adaptive) Experimental Treatment 1 Intervention

Participants will start with an 8-week run in period with vismodegib 150 mg dose by mouth daily. Participants will take vismodegib for the first 8 weeks, then start personalized dosing based on specific model.

Group III: Arm B: Fixed Intermittent Vismodegib Experimental Treatment 1 Intervention

Participants will receive intermittent 150 mg dose vismodegib by mouth with a 12 weeks on/8 weeks off regimen. Participants will take vismodegib for first 12 weeks, then off 8 weeks, and alternate in fixed cycles.

Group IV: A: Continuous Vismodegib Active Control 1 Intervention

Participants will receive continuous 150 mg by mouth daily vismodegib as per commercially available package insert.

Vismodegib is already approved in United States, European Union for the following indications:

Approved in United States as Erivedge for:

• Basal cell carcinoma (locally advanced or metastatic)

Approved in European Union as Erivedge for:

• Basal cell carcinoma (locally advanced or metastatic)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

In a real-world study of 63 patients with locally advanced or metastatic basal cell carcinoma (BCC), vismodegib demonstrated a high objective response rate (ORR) of 73%, with 57% achieving a partial response and 16% achieving a complete response.

While vismodegib was effective, 76.2% of patients experienced at least one adverse event, with common side effects including muscular spasms and dysgeusia, and serious adverse events occurred in 17% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety profile of vismodegib in a real-world setting cohort of patients with advanced basal cell carcinoma in Argentina. Cozzani, R., Del Aguila, R., Carrizo, M., et al.[2021]

Erivedge (vismodegib) was approved by the FDA for treating recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) based on a trial showing an overall response rate of 30.3% in metastatic cases and 42.9% in locally advanced cases, with median response durations of 7.6 months for both groups.

The treatment was generally well-tolerated, though common side effects included muscle spasms, alopecia, and fatigue; however, it is important to note that vismodegib is a potent teratogenic agent, indicating significant safety considerations for pregnant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. Axelson, M., Liu, K., Jiang, X., et al.[2022]

Vismodegib (Erivedge) is an effective treatment for advanced basal cell carcinoma, targeting the Hedgehog signaling pathway that is often overactive in this type of skin cancer.

Clinical studies have demonstrated that Vismodegib can lead to significant tumor shrinkage and improved outcomes for patients with advanced cases, highlighting its role as a key therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vismodegib (erivedge) for advanced Basal cell carcinoma. Fellner, C.[2023]

A review of the FDA Adverse Event Reporting System revealed a safety signal for hepatotoxicity associated with vismodegib, with 94 adverse event reports, including 35 serious cases, indicating potential liver-related risks in patients.

Despite the lack of formal safety notifications from the manufacturer or FDA, the findings suggest that vismodegib should be used cautiously in patients with severe liver disease and that hepatotoxic medications should be avoided to minimize serious liver complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on Adverse Drug Events and Reports Project. Edwards, BJ., Raisch, DW., Saraykar, SS., et al.[2018]

In a case series of 13 patients with locally advanced periocular basal cell carcinoma (BCC) treated with vismodegib, 38% achieved a complete response and 62% had a partial response, indicating its efficacy in managing this type of cancer.

Vismodegib was generally well-tolerated, with fatigue being the most common side effect, and it may allow for globe-sparing surgeries, potentially reducing the need for more drastic procedures like exenteration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vismodegib for periocular basal cell carcinoma: an international multicentre case series. Oliphant, H., Laybourne, J., Chan, K., et al.[2021]

A survey of oncologists and dermato-oncologists across several European countries showed that 95% of respondents in 2018 were aware of the teratogenic risks associated with vismodegib, indicating effective communication of safety information.

The majority of physicians (95% in 2018) reported taking appropriate precautions to minimize the risk of teratogenicity when prescribing vismodegib, demonstrating a strong adherence to safety protocols established by the Erivedge Pregnancy Prevention Program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vismodegib (ERIVEDGE) pregnancy prevention programme: assessment of risk awareness. Schnetzler, G., Cuberos, M., Bucher, R., et al.[2022]

Vismodegib is the first approved Hedgehog pathway inhibitor specifically for treating metastatic basal cell carcinoma (BCC) and advanced BCC that cannot be surgically removed or treated with radiation.

The drug's development is notable for its unique origins, which include natural sources like corn lilies and sheep, as well as research involving Drosophila flies, highlighting the diverse pathways leading to its discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vismodegib and the Hedgehog Pathway Inhibitors: A Historical Perspective to Current Clinical Application. Tang, JC., Hanke, CW., Caro, I.[2018]

References

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

Efficacy and safety profile of vismodegib in a real-world setting cohort of patients with advanced basal cell carcinoma in Argentina. [2021]

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

U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. [2022]

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

Vismodegib (erivedge) for advanced Basal cell carcinoma. [2023]

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

Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on Adverse Drug Events and Reports Project. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Vismodegib for periocular basal cell carcinoma: an international multicentre case series. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Vismodegib (ERIVEDGE) pregnancy prevention programme: assessment of risk awareness. [2022]

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

Vismodegib and the Hedgehog Pathway Inhibitors: A Historical Perspective to Current Clinical Application. [2018]