IRB Study Number 22-1288
Status Recruiting
Institutes Taussig Cancer Institute, Neurological Institute
Description
Primary Objectives:
To establish the MTD and/or RP2D of eflornithine in combination with TMZ
To determine the safety and tolerability of eflornithine in combination with TMZ following irradiation for GBM
Secondary Objectives:
To determine efficacy in patients treated with eflornithine in combination with TMZ as measured using response assessment in neuro-oncology (RANO) criteria
To determine the PK of eflornithine in patients with GBM
To explore any relationship between exposure and response
Inclusion Criteria
General Requirements
The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
Age ≥ 18 years.
GBM History
Diagnosis of World Health Organization (WHO) G4 classified GBM, IDH-wildtype per WHO 2021 tumor classification.
Confirmation of isocitrate dehydrogenase 1 gene (IDH1) wild type status based on historical standard of care immunohistochemistry or genetic sequencing.
Confirmation of O6-Methylguanine DNA methyltransferase (MGMT) methylation status based on historical standard of care testing.
Completed external beam radiation therapy per standard of care.
Toxicities from previous anti-cancer therapies must have resolved to baseline levels or to Grade 1 or less except for Grade 2 alopecia.
Must have received at least 80% of planned daily doses of TMZ during chemoradiation.
Current Medical Status
Karnofsky Performance Status (KPS) score of ≥ 80.
Adequate recovery from any major surgery is required; at least 4 weeks must have elapsed from the time of any major surgery and must have recovered from all surgery-related toxicities to grade ≤ 1 prior to enrollment.
Concomitant Medication
- If taking corticosteroids, must be on a stable or decreasing dose of ≤ 2 mg/day (dexamethasone) for at least 5 days prior to the screening MRI.
Organ Function
Adequate hematologic function (ANC ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 10.5 gm/dL). There must be a transfusion and growth factor free interval at least 7 days before C1D1.
Total bilirubin ≤ 1.5×upper limit of normal (ULN)
Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 2.5× ULN.
Adequate renal function (creatinine clearance ≥ 60 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation).
Amylase and Lipase ≤ 1.5 × ULN
Corrected QT interval using Fridericia’s formula (QTcF) ≤ 470 msec
Mean of baseline values, measured by Fridericia’s formula [QTcF = QT/(RR^0.33)]. If the QTcF is prolonged in a patient with a pacemaker or bundle branch block, the patient may be enrolled in the study if confirmed by the Medical Monitor.
Lifestyle
Female patients of childbearing potential must agree to utilize acceptable contraceptive methods from screening throughout the duration of the study period, and for 6 months following the last dose of study drugs. Abstinence is an acceptable method of contraception. Otherwise, consistent and current use of one of the following methods of birth control is accepted: oral contraceptive, intrauterine device, intrauterine hormone-releasing system, tubal sterilization, or vasectomy in the male partner. Female patients must also refrain from egg donation and in vitro fertilization during treatment and until at least 30 days from the last dose of study drugs.
Male patients must agree to abstain from sexual intercourse or use an acceptable contraceptive method (e.g., condoms) from screening throughout the duration of the study period, and for 90 days following the last dose of study drugs. Male patients must also refrain from sperm donation during treatment and until at least 90 days from the last dose of study drugs.
Exclusion Criteria
Medical History
History within the past 2 years of other cancer with metastatic or local recurrence potential that could negatively impact survival and or potentially confound response assessments. Patients with non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia and organ-confined prostate cancer deemed by the Investigator to be at low risk of recurrence are allowed.
Malabsorption syndrome, history of resection of the stomach or small bowel, active ulcerative colitis or Crohn’s disease, current partial or complete bowel obstruction or other conditions that would be expected to alter the absorption or pharmacokinetics of study drugs.
Prior Cancer Treatments
Prior systemic chemotherapy for GBM, other than TMZ during external beam radiation therapy, is not allowed.
Prior Optune treatment is not allowed.
During treatment with TMZ and radiation, any G4 event of anemia, neutropenia or thrombocytopenia, or any G3 event of neutropenia or thrombocytopenia lasting more than 7 days.
Current Medical Status
Presence of extracranial or leptomeningeal disease.
Active infection or serious intercurrent medical illness. Active infection is defined as the receipt of systemic antibiotic, antifungal or antiviral except for the purpose of prophylaxis. Patients must be COVID-19 negative.
Known or suspected infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Patients with well controlled HIV (e.g., CD4 > 350/mm3 and undetectable viral load) are eligible.
Current active liver disease from any cause, including hepatitis A (hepatitis A virus immunoglobulin M [IgM] positive), hepatitis B (hepatitis B virus [HBV] surface antigen positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV RNA). Patients with HCV with undetectable virus after treatment are eligible. Patients with prior exposure to HBV may be entered if quantitative PCR is negative.
Poorly controlled seizures as defined by persistence of seizures following initiation of medication.
Unable to undergo an MRI with contrast.
Any of the following within 6 months prior to the first dose of study drugs:
a. Myocardial infarction
b. Unstable angina
c. Unstable symptomatic ischemic heart disease
d. New York Heart Association Class III or IV heart failure
e. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events). Exception: adequately treated catheter related thrombosis
f. Any other significant cardiac condition (e.g., pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart disease)
g. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator
h. Pneumonitis
Patients with poorly controlled diabetes.
Pregnant or breastfeeding.
Prior and Concomitant Medication
Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 μg (Note: Patients who switch from a high dose to a dose of 30 μg/day or less at least 1 day prior to Screening assessments are eligible for study entry).
Use of any investigational agent within 30 days prior to enrollment.
