Vismodegib for Basal Cell Carcinoma

Overseen By Sy Olson-Mcpeek

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of different dosing schedules of the drug vismodegib for individuals with advanced basal cell carcinoma, a type of skin cancer. The study compares two personalized dosing plans with both a fixed intermittent schedule and a continuous daily dose to determine which is more effective and better tolerated. It suits those diagnosed with advanced basal cell carcinoma who have at least one measurable skin tumor. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vismodegib is generally safe for treating advanced basal cell carcinoma. Studies have found that patients with this condition usually tolerate the drug well. For example, in one study with 33 patients, 58% showed improvement, meaning more than half got better. Another report from a Spanish center over three years also confirmed its safety and effectiveness.

However, important safety concerns exist. Vismodegib carries a warning about embryo-fetal toxicity, indicating it can cause serious birth defects if taken during pregnancy. Other common side effects may include muscle spasms, hair loss, and tiredness. Overall, while vismodegib is considered safe for most people, discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for basal cell carcinoma involve surgical removal or topical therapies. But vismodegib works differently, targeting the Hedgehog signaling pathway, which is crucial for the growth of cancer cells. Researchers are excited about this treatment because it offers a non-surgical oral option that could be personalized based on individual response. This means patients might avoid surgery and still effectively manage their condition. Additionally, the personalized dosing plans—intermittent and adaptive dosing—may reduce side effects compared to continuous dosing while maintaining effectiveness.

What evidence suggests that this trial's treatments could be effective for basal cell carcinoma?

Research has shown that vismodegib may effectively treat advanced basal cell carcinoma, a type of skin cancer. One study found that 58% of patients experienced tumor shrinkage or disappearance after treatment. This trial will explore different dosing strategies of vismodegib. Participants in one arm will receive continuous dosing, while others will test intermittent dosing strategies, which previous studies found effective and manageable. Additionally, long-term use of vismodegib has been successful for many patients, with manageable side effects. These findings suggest that vismodegib could be a strong option for managing this condition. ^{2 6 7 8 9}

Who Is on the Research Team?

Zeynep Eroglu

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1113713

Efficacy and Safety of Vismodegib in Advanced Basal-Cell ... A phase 1 study of vismodegib involving 33 patients with advanced basal-cell carcinoma showed a 58% confirmed response rate and a median duration of response ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4211514/

Long-term safety, tolerability, and efficacy of vismodegib in ... Overall, based on data from these two patients, it appears that long-term vismodegib use in adults with advanced BCC can be an effective therapy with manageable ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8918118/

New Emerging Treatment Options for Advanced Basal Cell ... Moreover, vismodegib showed promising results in terms of efficacy and safety also when administered at a long-intermittent dosing regimen [24].

4. erivedge.com erivedge.com/content/dam/gene/erivedge/hcp/pdfs/patient_case_series_2.pdf

Case studies in advanced basal cell carcinoma (BCC) The safety data described below reflect exposure to ERIVEDGE in 138 patients with advanced basal cell carcinoma (BCC) who received ERIVEDGE at doses ≥ 150 mg ...

5. jaad.org jaad.org/article/S0190-9622(22)00505-9/fulltext

Advanced basal cell carcinoma: What dermatologists need ... Vismodegib achieved an objective response rate (ORR) (complete response or partial response) of 30%, based on independent review, in the metastatic BCC group ...

6. erivedge.com erivedge.com/hcp/side-effects/important-safety-information.html

Important Safety Information | Erivedge® (vismodegib) Important Safety Information. BOXED WARNING: EMBRYO-FETAL TOXICITY. Erivedge can cause embryo-fetal death or severe birth defects when administered to a ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37239551/

3-Year Experience from a Spanish Center Conclusions: Vismodegib is a safe and effective treatment for locally advanced BCC, and its role in unresectable BCC seems to be an important ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00833417

NCT00833417 | A Study Evaluating the Efficacy and Safety ... A Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma. ClinicalTrials.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/203388s017lbl.pdf

1 of 12 This label may not be the latest approved by FDA. For ... The safety data described below reflect exposure to ERIVEDGE in 138 patients with advanced basal cell carcinoma (BCC) who received ERIVEDGE at doses ≥ 150 ...