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

35 Participants Needed

Trial Summary

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.

What makes the drug Vismodegib unique for treating cancer?

Vismodegib is unique because it targets the Hedgehog signaling pathway, which is involved in the growth of certain cancer cells, making it different from traditional chemotherapy that targets rapidly dividing cells in general. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II MATCH treatment trial tests how well GDC-0449 (vismodegib) works for treating patients with solid tumors, lymphoma, or multiple myeloma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that does not respond to treatment (refractory) and who have a smoothened or patched 1 genetic mutation. Vismodegib is a type of medication called a hedgehog signaling pathway antagonist and works by blocks a type of protein involved in tissue growth and repair and may block the growth of cancer cells.

Research Team

Anne S Tsao

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

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

Synthesis and activity of tumor-homing peptide iRGD and histone deacetylase inhibitor valproic acid conjugate. [2021]

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

Arg-Gly-Asp (RGD)-Modified E1A/E1B Double Mutant Adenovirus Enhances Antitumor Activity in Prostate Cancer Cells In Vitro and in Mice. [2018]

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

The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells. [2018]

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

Experimental Study of Antitumor Activity of Pefagtal Addressed to αvβ3 Integrins. [2022]

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

Integrin antagonist augments the therapeutic effect of adenovirus-mediated REIC/Dkk-3 gene therapy for malignant glioma. [2020]