RECRUITING

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

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Conditions

IDH Wildtype GlioblastomaRecurrent AstrocytomaIDH Wildtype Recurrent GlioblastomaResectable AstrocytomaResectable Glioblastoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2025-07-28
Study Completion:2028-07-30
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT07089641

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Patients must be 18 years of age or older on the day of signing informed consent
  2. * Patients must have histologically proven surgically accessible World Health Organization (WHO) grade IV glioblastoma/astrocytoma, which is progressive or recurrent following radiation therapy +/- chemotherapy
  3. * Patient tumor sample must have wild type IDH with evidence of EGFR mutation/amplification by Clinical Laboratory Improvement Act (CLIA)-certified laboratory assay
  4. * Patients may have had no more than two prior recurrences
  5. * Patient must be able to tolerate MRIs. Pre-study enrollment MRIs must be available for central review, including at least the immediate pre-progression scan and the scan demonstrating progression. Patients must have measurable, by RANO, supratentorial contrast-enhancing progressive or recurrent high-grade glioma by MRI imaging within 7 days of starting treatment
  6. * Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:
  7. * 12 weeks from the completion of radiation
  8. * 6 weeks from a nitrosourea chemotherapy
  9. * 3 weeks from a non-nitrosourea chemotherapy
  10. * 4 weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
  11. * 4 weeks from the last treatment with bevacizumab
  12. * 2 weeks from administration of a non-cytotoxic, FDA-approved agent other than bevacizumab (e.g., hydroxychloroquine, etc.)
  13. * 1 week from the tumor treating fields
  14. * Patients must be undergoing surgery that is clinically indicated as determined by their care providers. Patients must be eligible for surgical resection according to the following criteria:
  15. * Expectation that the surgeon can resect at least 500 mg of tumor from enhancing tumor and 100 mg from non-enhancing tumor with low risk of inducing neurological injury
  16. * Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment). The following amount of tissue is requested: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 30 FFPE unstained slides (5µm thick)
  17. * Patients must have a Karnofsky performance status ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  18. * Absolute neutrophil count (ANC) ≥ 1000/uL
  19. * Platelets ≥ 100,000/uL
  20. * Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L
  21. * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
  22. * Creatinine ≤ 1 x upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥ 30 mL/min for participant with creatinine levels \> 1 x institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\])
  23. * Creatinine clearance (CrCl) should be calculated per institutional standard
  24. * Total bilirubin ≤ 1.5 x ULN unless with Gilbert's syndrome
  25. * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x ULN
  26. * International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  27. * Patients must have left ventricular ejection fraction (LVEF) within normal institutional limits within 21 days of starting treatment
  28. * Patients must have a 12-lead electrocardiogram performed within 2 weeks of treatment start with Fridericia's formula-corrected QT interval (QTcF) \< 450 msec
  29. * Patients must be able to provide written informed consent
  30. * Women of childbearing potential must have a negative urine or serum pregnancy test 7 days prior to the first dose
  31. * Women of childbearing potential and men must agree to use adequate method of contraception for the duration of study participation and for 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after the last dose of study drug
  32. * Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with prior malignancies must be disease-free for \> three years
  33. * Patients must be able to swallow medication by mouth
  1. * Participants may not be receiving any other investigational agents
  2. * Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ERAS-801 are ineligible
  3. * Participants with prior therapy with EGFR inhibitors are ineligible because treatment with EGFR kinase inhibitors or other EGFR-targeted agents has the potential to deplete the tumor of EGFR-amplified or EGFR mutant cell populations and confound the evaluation of ERAS-801 effects on participants
  4. * Participants on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol. Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of ERAS-801
  5. * Participants must not have evidence of significant hematologic, renal, or hepatic dysfunction
  6. * Participants must not have evidence of significant intracranial hemorrhage
  7. * Participants with clinically significant cardiovascular disease including, but not limited to:
  8. * Myocardial infarction or unstable angina within the 6 months prior to the first dose of study drug
  9. * Clinically significant cardiac arrhythmia
  10. * Prolonged QTcF \> 450 ms
  11. * Uncontrolled (persistent) hypertension: systolic blood pressure \> 180 mmHg; diastolic blood pressure \> 100 mmHg
  12. * Congestive heart failure (New York Heart Association class III-IV)
  13. * Use of pacemaker
  14. * Pulmonary embolism \< 30 days
  15. * Participants with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
  16. * Pregnant women are excluded from this study because ERAS-801 has unknown potential for teratogenic or abortifacients effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ERAS-801, breastfeeding should be discontinued if the mother is treated with ERAS-801
  17. * Participants currently using or anticipating need to use drugs, food, or herbal supplements known to be strong or moderate inducers or inhibitors of CYP3A4, CYP2C8, and/or CYP2D6 and P-glycoprotein (P-gp) substrates within 10 days of study enrollment are ineligible
  18. * Participants who have acute or currently active/requiring anti-viral therapy hepatic or biliary disease are ineligible (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases from the primary brain tumor, or stable chronic liver disease per investigator assessment)
  19. * Patients with gastrointestinal conditions that may affect reliable administration/absorption of medications including difficulty swallowing/unable to swallow pills; malabsorption syndrome; refractory nausea and vomiting, chronic gastrointestinal (GI) disease or previous significant bowel resection with clinically significant sequelae are ineligible
  20. * Participants receiving P-gp inhibitors are ineligible
  21. * Patients who have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial are ineligible

Contacts and Locations

Study Contact

Soheila Abbassi
CONTACT
310-267-3106
SAbbassi@mednet.ucla.edu

Principal Investigator

Phioanh Nghiemphu
PRINCIPAL_INVESTIGATOR
UCLA / Jonsson Comprehensive Cancer Center

Study Locations (Sites)

UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
United States

Collaborators and Investigators

Sponsor: Jonsson Comprehensive Cancer Center

  • Phioanh Nghiemphu, PRINCIPAL_INVESTIGATOR, UCLA / Jonsson Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-28
Study Completion Date2028-07-30

Study Record Updates

Study Start Date2025-07-28
Study Completion Date2028-07-30

Terms related to this study

Additional Relevant MeSH Terms

  • IDH Wildtype Glioblastoma
  • Recurrent Astrocytoma
  • IDH Wildtype Recurrent Glioblastoma
  • Resectable Astrocytoma
  • Resectable Glioblastoma