Testing GDC-0449 (Vismodegib) as Potentially Targeted Treatment in Cancers With Smoothened or Patched 1 Mutant Tumors (MATCH - Subprotocol T)

NCT ID: NCT06357988

Last Updated: 2025-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-24

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

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 echocardiography (ECHO) or nuclear study during screening, tumor biopsy on study and computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for year 3.

Conditions

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Advanced Lymphoma Advanced Malignant Solid Neoplasm Hematopoietic and Lymphatic System Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (Vismodegib)

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.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo tumor biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Echocardiography Test

Intervention Type PROCEDURE

Undergo echocardiography

Radionuclide Imaging

Intervention Type PROCEDURE

Undergo nuclear study

Vismodegib

Intervention Type DRUG

Given PO

Interventions

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Biopsy Procedure

Undergo tumor biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Echocardiography Test

Undergo echocardiography

Intervention Type PROCEDURE

Radionuclide Imaging

Undergo nuclear study

Intervention Type PROCEDURE

Vismodegib

Given PO

Intervention Type DRUG

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection EC Echocardiography NM Nuclear Medicine nuclear medicine scan radioimaging Radionuclide Scanning Scan Scintigraphy Erivedge GDC 0449 GDC-0449 GDC0449 Hedgehog Antagonist GDC-0449

Eligibility Criteria

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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 activating mutations of smoothened (SMO) or deleterious Patched 1 (PTCH1) as determined via the MATCH Master protocol and described in appendix II. See appendix II for information on the smoothened (SMO) or patched 1 (PTCH1) mutations and corresponding levels of evidence
* Patient must not have basal cell carcinoma
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anne S Tsao

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2024-01149

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAY131-T

Identifier Type: OTHER

Identifier Source: secondary_id

EAY131-T

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-01149

Identifier Type: -

Identifier Source: org_study_id

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