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Trials / Recruiting

RecruitingNCT07089641

ERAS-801 for the Treatment of Resectable and Progressive or Recurrent IDH Wildtype Grade IV Glioblastoma or Astrocytoma With an EGFR Amplification or Mutation, ERAS801-SARG Trial

A Phase Ib Open Label Clinical Trial to Evaluate the Safety and Efficacy of ERAS-801 in Surgically Accessible Recurrent Glioblastoma Patients With EGFR Amplification or Mutation (ERAS801-SARG)

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
10 (estimated)
Sponsor
Jonsson Comprehensive Cancer Center · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase Ib trial tests the safety and side effects of ERAS-801 in treating patients with isocitrate dehydrogenase (IDH) wildtype, epidermal growth factor receptor (EGFR) amplified or mutated grade IV glioblastoma or astrocytoma that can be removed by surgery (resectable) and that is growing, spreading, or getting worse (progressive) or that has come back after a period of improvement (recurrent). Glioblastoma is the most common brain cancer in adults and survival rates remain poor despite treatment including surgery, radiation and chemotherapy. EGFR is a protein found on the surface of some cells, to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of tumor cells, so these cells may divide excessively in the presence of epidermal growth factor. ERAS-801, an EGFR inhibitor that can penetrate the central nervous system, binds to the tumor cells that express EGFR and may help shrink or slow the growth of the tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the glucose utilization in the tumor from the glioblastoma patients treated with EGFR inhibitor ERAS-801 (ERAS-801). II. To evaluate the influence of ERAS-801 treatment on the apoptotic machinery in recurrent glioblastoma. III. To evaluate the safety and tolerability of ERAS-801 recommended phase 2 dose (RP2D) in recurrent glioblastoma. SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetic (PK) profile in plasma, cerebrospinal fluid (CSF), and tumor tissue of ERAS-801 in recurrent glioblastomas. II. To evaluate the pharmacodynamic (PD) impact of ERAS-801 treatment in recurrent glioblastomas. III. To evaluate whether glycolytic index (GI) measured by fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) and metabolic magnetic resonance imaging (MRI) correlates with clinical responses in recurrent glioblastomas treated with ERAS-801. IV. To evaluate whether potential of hydrogen (pH)-weighted chemical exchange saturation transfer (CEST)-spin-and-gradient echo (SAGE)-echoplanar imaging (EPI) contrast measured by metabolic MRI correlates with clinical responses in recurrent glioblastomas treated with ERAS-801. EXPLORATORY OBJECTIVES: I. To evaluate the associations between exploratory biomarkers, clinical outcomes, and adverse events which include: Ia. Estimating the efficacy of ERAS-801 through 6 month progression free survival (PFS6), progression free survival (PFS), and overall survival (OS) as defined by modified Response Assessment in Neuro-Oncology criteria (mRANO)/Response Assessment in Neuro-Oncology criteria (RANO) 2.0; Ib. Exploring whether glycolytic index (GI) and pH-weighted CEST-SAGE-EPI contrast correlates with clinical responses; Ic. Exploring whether there are alterations of key glycolytic enzymes and/or other transcriptional changes linked to EGFR occur with ERAS-801 treatment; Id. Exploring whether there are changes in percent of tumor cells that have immunohistochemical positive staining for the KI67 antigen after ERAS-801 treatment; Ie. Exploring the associations between the various biomarker evaluations (tissue and imaging), clinical outcome measures and adverse events. OUTLINE: Patients receive ERAS-801 orally (PO) once daily (QD) for 8-14 days prior to undergoing scheduled surgical resection. Starting no more than 28 days after surgery, patients then receive ERAS-801 PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO), urine and blood sample collection and brain MRI throughout the study. Additionally, patients undergo CSF sample collection at the time of surgery and FDG PET on study. After completion of study treatment, patients are followed up at 30 days, then every 2 months up to documented disease progression, death, or the end of the study. Patients with disease progression are followed up every 12 weeks up to death, withdrawal of consent, or the end of the trial, whichever, occurs first.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiospecimen CollectionUndergo urine, blood, and CSF sample collection
PROCEDUREEchocardiography TestUndergo ECHO
DRUGEGFR Inhibitor ERAS-801Given PO
OTHERFludeoxyglucose F-18Given FDG
PROCEDUREMagnetic Resonance ImagingUndergo brain MRI
PROCEDUREPositron Emission TomographyUndergo FDG PET
PROCEDURESurgical ProcedureUndergo surgical resection

Timeline

Start date
2025-07-28
Primary completion
2027-07-30
Completion
2028-07-30
First posted
2025-07-28
Last updated
2026-04-07

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT07089641. Inclusion in this directory is not an endorsement.