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

NCT06357988 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: NCI-2024-01149EAY131-TU10CA180820
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.

  Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Secondary Outcomes (2)

• 6-month Progression-free Survival (PFS) Rate

  Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined

• Progression Free Survival

  Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Study Arms (1)

Treatment (Vismodegib)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Procedure: Radionuclide Imaging; Drug: Vismodegib

Interventions

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (Vismodegib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Vismodegib)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (Vismodegib)

Radionuclide Imaging PROCEDURE

Undergo nuclear study

Also known as: Gamma Scan, NM, Nuclear Medicine, nuclear medicine scan, radioimaging, Radionuclide Scanning, Scan, Scintigraphy

Treatment (Vismodegib)

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC 0449, GDC-0449, GDC0449, Hedgehog Antagonist GDC-0449

Treatment (Vismodegib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma

Interventions

Biopsy; Specimen Handling; Nuclear Medicine Department, Hospital; HhAntag691

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Hospital Administration; Health Facility Administration; Organization and Administration; Health Services Administration

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Cancer Research Group

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Anne S Tsao

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2024
• First Posted: April 10, 2024
• Study Start: June 20, 2016
• Primary Completion: November 4, 2022
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2026
• Results First Posted: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)