Inclusion Criteria:
- - Patients must be 18 years of age or older on the day of signing informed consent.
- - Patients must have histologically proven surgically accessible World Health
Organization (WHO) grade IV glioblastoma/astrocytoma, which is progressive or
recurrent following radiation therapy +/- chemotherapy.
- - Patient tumor sample must have wild type IDH with evidence of EGFR
mutation/amplification by Clinical Laboratory Improvement Act (CLIA)-certified
laboratory assay.
- - Patients may have had no more than two prior recurrences.
- - 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.
- - Patients must have recovered from severe toxicity of prior therapy.
The following
intervals from previous treatments are required to be eligible:
- - 12 weeks from the completion of radiation.
- - 6 weeks from a nitrosourea chemotherapy.
- - 3 weeks from a non-nitrosourea chemotherapy.
- - 4 weeks from any investigational (not Food and Drug Administration
[FDA]-approved) agents.
- - 4 weeks from the last treatment with bevacizumab.
- - 2 weeks from administration of a non-cytotoxic, FDA-approved agent other than
bevacizumab (e.g., hydroxychloroquine, etc.)
- 1 week from the tumor treating fields.
- - 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:
- - 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.
- - 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)
- - 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)
- Absolute neutrophil count (ANC) ≥ 1000/uL.
- - Platelets ≥ 100,000/uL.
- - Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L.
- - Criteria must be met without erythropoietin dependency and without packed red
blood cell (pRBC) transfusion within last 2 weeks.
- - 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])
- Creatinine clearance (CrCl) should be calculated per institutional standard.
- - Total bilirubin ≤ 1.5 x ULN unless with Gilbert's syndrome.
- - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3
x ULN.
- - 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.
- - Patients must have left ventricular ejection fraction (LVEF) within normal
institutional limits within 21 days of starting treatment.
- - Patients must have a 12-lead electrocardiogram performed within 2 weeks of treatment
start with Fridericia's formula-corrected QT interval (QTcF) < 450 msec.
- - Patients must be able to provide written informed consent.
- - Women of childbearing potential must have a negative urine or serum pregnancy test 7
days prior to the first dose.
- - 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.
- - 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.
- - Patients must be able to swallow medication by mouth.
Exclusion Criteria:
- - Participants may not be receiving any other investigational agents.
- - Participants with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to ERAS-801 are ineligible.
- - 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.
- - 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.
- - Participants must not have evidence of significant hematologic, renal, or hepatic
dysfunction.
- - Participants must not have evidence of significant intracranial hemorrhage.
- - Participants with clinically significant cardiovascular disease including, but not
limited to:
- Myocardial infarction or unstable angina within the 6 months prior to the first
dose of study drug.
- - Clinically significant cardiac arrhythmia.
- - Prolonged QTcF > 450 ms.
- - Uncontrolled (persistent) hypertension: systolic blood pressure > 180 mmHg;
diastolic blood pressure > 100 mmHg.
- - Congestive heart failure (New York Heart Association class III-IV)
- Use of pacemaker.
- - Pulmonary embolism < 30 days.
- - 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.
- - 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.
- - 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.
- - 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)
- 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.
- - Participants receiving P-gp inhibitors are ineligible.
- Patients who have known psychiatric or substance abuse disorders that would
interfere with cooperation with the requirements of the trial are ineligible
