Inclusion Criteria:
- - Patients must have histologically confirmed World Health Organization (WHO) grade 2-4
glioma, isocitrate dehydrogenase (IDH) wild type (WT) (by immunohistochemistry [IHC]
R132H negative [neg] or sequencing).
Astrocytoma with molecular features of
glioblastoma (GBM). Confirmed diagnosis via molecular testing.
- - Patients must have an established diagnosis of recurrent glioblastoma and:
- Group 1 and 2: recurrent glioblastoma.
- - Group 3: Surgically amenable recurrent glioblastoma.
- - Patients must have stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg
dexamethasone, for ≥ 7 days prior to registration.
- - Patients with disease that has progressed after a standard or investigational
first-line therapy (e.g. radiotherapy [RT], RT plus temozolomide) with or without
tumor treating fields therapy (TTFields)
- Note: Patients who have received fractionated first-line radiation therapy and no
prior chemotherapy (e.g. as common practice for MGMT unmethylated tumors), or who
have participated in an investigational protocol substituting TMZ for a novel
agent are eligible.
- - Patients must be able to undergo contrast-enhanced magnetic resonance imaging (MRI)
- Patients must be age ≥ 18 years.
- - Patients must exhibit a Karnofsky performance status ≥ 70.
- - Leukocytes (white blood cells [WBC]) ≥ 3,000/mcL.
- - Absolute neutrophil count (ANC) ≥ 1,500/mcL.
- - Hemoglobin (Hgb) ≥ 8 g/dL (transfusion may be used for eligibility outside of 7 days)
- Platelets (PLT) ≥ 100,000/mcL (transfusion or growth factor may be used for
eligibility outside of 7 days)
- Total bilirubin ≤ 2 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
≤ 3 x institutional ULN.
- - Creatinine ≤ 1.5 x institutional ULN.
- - International normalized ratio (INR) ≤ 1.5 x ULN.
- - Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 x ULN.
- - Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification.
To be
eligible for this trial, patients should be class 2B or better.
- - Patients of child-bearing potential (POCBP) must agree to use two forms of adequate
contraception (hormonal or barrier method of birth control, abstinence) from time of
informed consent and for the duration of study participation.
Patients who can
impregnate their partners must agree to use adequate contraception (hormonal or
barrier method of birth control, abstinence) from time of informed consent and for the
duration of study participation.
- - Should a patient become pregnant or suspect they are pregnant while they or their
partner is participating in this study, they should inform their treating
physician immediately.
- - Note: At the discretion of the investigator, acceptable methods of contraception
may include total abstinence in cases where the lifestyle of the patient ensures
compliance.
(Periodic abstinence [e.g., calendar, ovulation, symptothermal,
postovulation methods] and withdrawal are not acceptable methods of
contraception.)
- - Note: A POCBP is any person with an egg-producing reproductive tract (regardless
of gender, sexual orientation, having undergone a tubal ligation, or remaining
celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy, bilateral salpingectomy, or bilateral
oophorectomy.
- - Has had menses at any time in the preceding 12 consecutive months (and
therefore has not been naturally postmenopausal for > 12 months) (in
patients > 45 years of age in the absence of other biological or
physiological causes)
- Potential POCBP who may be menopausal and are < 55 years of age must
have a serum follicle-stimulating hormone (FSH) level > 40 mIU/mL to
confirm menopause.
- - Note: Documentation may include review of medical records, medical
examination, or medical history interview by study site staff.
- - Patient must be willing and able to comply with the protocol for the duration of the
study and provide written, signed, and dated informed consent prior to study
registration.
- - NOTE: No study-specific screening procedures may be performed until written
consent has been obtained.
- - Patients must have the ability to understand and the willingness to sign a written
informed consent document.
Exclusion Criteria:
- - Patients who have a prior or concurrent malignancy that may interfere with study
treatment or safety.
- - NOTE: Patients with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible, per principal
investigator (PI) discretion.
- - Patients who are receiving any other investigational agents.
- - Exceptions: COVID-19 vaccine and treatment is allowed, per PI's discretion.
- - Patient's interval since last cytotoxic therapy ≥ 1 cycle or ≥ 2 biological
half-lives, i.e.
- ≥ 28 days since start of last cycle of temozolomide (cycle length-28 days)
- ≥ 42 days since start of last cycle of lomustine or other nitrosourea (cycle
length-42 days)
- ≥ 21 days since start of last cycle of a small molecule targeted agent (cycle
length-21 days)
- ≥ 42 days from last bevacizumab infusion (cycle length-42 days)
- Patients who have a history of allergic reactions attributed to compounds of similar
chemical composition to temozolomide or triapine.
- - Patients with spinal cord and diffuse leptomeningeal dissemination.
- - Patients with a history of G6PD deficiency or other congenital or autoimmune hemolytic
disorders.
All participants will be screened for G6PD levels prior to registration.
- - Patients who have an uncontrolled intercurrent illness including, but not limited to
any of the following:
- Have uncontrolled epilepsy.
- - Have an uncontrolled intercurrent illness.
- - Are pregnant or nursing.
- - Concurrent malignancy (outside of glioblastoma) that requires tumor directed
treatment.
- - Known concurrent shingles, herpes, cytomegalovirus (CMV) infection.
- - Known concurrent opportunistic fungal infection.
- - Known immunodeficiency that could lead to opportunistic infections.
- - Psychiatric illness/social situations that would limit compliance with study
requirements.
- - Any other illness or condition that the treating investigator feels would
interfere with study compliance or would compromise the patient's safety or study
endpoints.
- - Patients who are pregnant or nursing.
Pregnant patients are excluded from this study
because temozolomide is an alkylating agent with potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with temozolomide,
breastfeeding should be discontinued if the mother is treated with temozolomide.
- - Patients who are unable to swallow oral medication or have problems/diseases that
affect absorption or oral medication.
- - Patients with a known history of human immunodeficiency virus (HIV), hepatitis B virus
(HBV), and/or hepatitis C virus (HCV).
If patient does not have a known history
testing will not be conducted.
- - Note: Temozolomide is an immunosuppressive agent.
Patients with a known history
of HIV, HBV, and HCV, and unexplained opportunistic infections are not eligible
due to safety reasons
