Vismodegib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Basal cell carcinoma, Cardiac abnormalities, Hypersensitivity, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a drug called vismodegib for individuals with certain advanced or hard-to-treat cancers. Vismodegib targets a specific pathway in the body that aids cancer cell growth, potentially halting their spread. Suitable candidates for this trial have solid tumors, lymphoma, or multiple myeloma that have not responded well to other treatments and possess specific genetic mutations in the SMO or PTCH1 genes, excluding those with basal cell carcinoma. Participants will take vismodegib daily and undergo various tests to monitor the treatment's effects. As a Phase 2 trial, this research focuses on assessing the treatment's efficacy in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that vismodegib is generally safe for people. Studies on patients with advanced basal cell carcinoma, a type of skin cancer, provide some insights. In these studies, vismodegib proved to be quite safe.

For example, one study with 33 patients showed a positive response to the treatment. Another study confirmed its safety over a longer period. Patients experienced some side effects, but these were mostly manageable. Common side effects included muscle cramps, hair loss, and changes in taste.

Vismodegib is already approved by the FDA for treating advanced basal cell carcinoma, indicating a level of safety based on previous research. However, like any medication, monitoring for side effects and discussing them with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Vismodegib is unique because it specifically targets the Hedgehog signaling pathway, which is often activated in certain types of cancer. Unlike traditional chemotherapy that attacks rapidly dividing cells in general, vismodegib directly inhibits a protein called Smoothened, interfering with cancer cell growth more precisely. Researchers are excited about this treatment because it offers a more targeted approach, potentially resulting in fewer side effects compared to standard treatments like surgery, radiation, or broad-spectrum chemotherapy.

What evidence suggests that vismodegib might be an effective treatment for advanced or refractory cancer?

Research has shown that vismodegib, the treatment under study in this trial, may help treat certain types of cancer. In studies with patients who had advanced basal-cell carcinoma, vismodegib shrank tumors in 58% of the patients, meaning more than half saw improvement. This treatment blocks the hedgehog signaling pathway, which plays a role in cancer cell growth. By doing so, vismodegib may help stop or slow the spread of cancer. While its effectiveness in other advanced cancers like solid tumors, lymphoma, and multiple myeloma is still under investigation, these early results suggest it could be beneficial. ^{1 5 6 7 8}

Who Is on the Research Team?

Anne S Tsao

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for patients with advanced or treatment-resistant solid tumors, lymphoma, or multiple myeloma that have specific genetic mutations (smoothened or patched 1). Participants should have a tumor amenable to biopsy and must not be receiving other cancer treatments.

Inclusion Criteria

Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol

Patients must fulfill all eligibility criteria outlined in section 3.1 of MATCH Master protocol (excluding section 3.1.6) at the time of registration to treatment step (step 1, 3, 5, 7)

Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have NONE of the following cardiac criteria: No clinically unstable abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block; No factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events such as congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age; Patients with known left ventricular dysfunction must have ECHO or nuclear study (multigated acquisition [MUGA] scan or first pass) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible; Patients must not have known hypersensitivity to GDC-0449 (vismodegib) or compounds of similar chemical or biologic composition; Women of childbearing potential and men who are sexually active must agree to use adequate contraception defined as appropriate double barrier method of birth control (such as female use of a diaphragm, intrauterine device (IUD), sponge and spermicide, in addition to the male use of a condom or involve female use of prescribed 'birth control pills' or a prescribed birth control implant). Both double barrier contraception and birth control pills or implants must be used for at least one week prior to the start of the study and continue for 24 months after completion of study for women, and 3 months after completion of study for men

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive vismodegib orally daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Regular visits for tumor biopsy, CT scan, MRI, and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years

Every 3 months for 2 years, then every 6 months for year 3

What Are the Treatments Tested in This Trial?

Interventions

• Vismodegib

Trial Overview The study is testing the effectiveness of Vismodegib, a drug that targets the hedgehog signaling pathway which may inhibit cancer growth. It includes procedures like biopsies and heart monitoring through echocardiography to assess its impact on various cancers.

How Is the Trial Designed?

Group I: Treatment (Vismodegib) Experimental Treatment 5 Interventions

Patients receive vismodegib orally (PO) daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or nuclear study during screening, tumor biopsy on study and CT scan, MRI and blood sample collection throughout the study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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/PMC10218270/

Retrospective Real-Life Data, Efficacy and Safety of ... Conclusions: Vismodegib is a safe and effective treatment for locally advanced BCC, and its role in unresectable BCC seems to be an important ...

3. erivedge.com erivedge.com/hcp/efficacy/clinical-results.html

Clinical Results | Erivedge® (vismodegib) Erivedge® (vismodegib) clinical results for patients with locally advanced and metastatic basal cell carcinoma. See full safety & Boxed Warning.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01239316

Vismodegib in Treating Younger Patients With Recurrent or ... This phase II trial studies how well vismodegib works in treating younger patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S246829422400008X;

Exploring vismodegib: A non-surgical breakthrough in the ... The outcome was not evaluable or not available in 6.1 % of the patients. An overall response rate of 33 % was reported on metastatic BCC across all trials, with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28511673/

final update of the pivotal ERIVANCE BCC study Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study.

7. 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.

8. 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 ...