Inclusion Criteria:
- - Participants must have histologically proven glioblastoma or gliosarcoma which is
progressive or recurrent following radiation therapy +/- chemotherapy.
- - Participants must have evaluable, supratentorial contrast-enhancing progressive or
recurrent glioblastoma or gliosarcoma by magnetic resonance imaging (MRI) imaging
within 14 days of study treatment initiation.
Participants must be able to tolerate
MRIs.
- - Participants can have any number of prior relapses.
- - Participants 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 or mitomycin C.
- - 23 days from temozolomide chemotherapy.
- - 4-weeks from other cytotoxic therapy unless noted above.
- - 4 weeks or 5-half-lives (whichever is shorter) from any other investigational
(not Food and Drug Administration [FDA]-approved) agents (including vaccines)
- Participants must be undergoing surgery that is clinically indicated as determined
by their care providers.
Patients must be eligible for surgical resection with the
expectation that the surgeon is able to resect at least 300 mg of tumor with low
risk of inducing neurological injury.
- - Participants must be undergoing radiotherapy that is clinically indicated as
determined by their care providers.
The field of radiation must overlap the area of
tumor planned for surgical resection. Participants must have a minimum tumor size of
2 x 2 cm^2 based on MRI scan prior to surgery.
- - Participants must be 18 years of age or older.
- - Participants must have a Karnofsky performance status >= 60% (i.e. the participant
must be able to care for himself/herself with occasional help from others)
- Absolute neutrophil count >= 1,500/mcL.
- - Platelets >= 100,000/mcL.
- - Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) /
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x
institutional upper limit of normal.
- - Creatinine =< institutional upper limit of normal OR creatinine clearance >= 50
mL/min/1.73m^2 for patients with creatinine levels above institutional normal.
- - Activated partial thromboplastin time/ partial thromboplastin time (APTT/PTT) =< 1.5
x institutional upper limit of normal (unless participant is receiving anticoagulant
therapy as long as prothrombin time [PT] or aPTT is within therapeutic range of
intended use of anticoagulants)
- Female participants of childbearing potential must have a negative urine or serum
pregnancy test prior to study entry.
Women are considered post-menopausal and not of
child bearing potential if they have had 12 months of natural (spontaneous)
amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of
vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle
stimulating hormone [FSH] levels > 40 mIU/mL and estradiol < 20 pg/mL or have had
surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks
ago. In the case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential.
- - Female participants of childbearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry, for the duration of study participation, and through 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
through 30 days after the last dose of study drug.
Women who are nursing should
discontinue nursing prior to starting study drug.
- - Participants 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.
- - Participants must be able to swallow whole capsules.
- - Participants must have at least 20 (preferably 40) slides of archival tumor tissue
from a prior surgery demonstrating GBM.
- - Participants must have the ability to understand and the willingness to sign a
written informed consent document.
Exclusion Criteria:
- - Participants receiving any other investigational agents or using an investigational
device are ineligible.
- - Participants with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to ONC201 are ineligible.
- - Participants may not have had prior treatment with ONC201.
- - Participants may have had prior treatment with bevacizumab/VEGFR inhibitors, but
last dose of treatment must be at least 4 weeks prior to the date of planned tumor
resection.
- - Participants may not be on concurrent treatment with Optune device.
Prior use of the
device is allowable.
- - Participants must not have evidence of significant hematologic, renal, or hepatic
dysfunction.
- - Participants with a history of any of the following within the last 6 months prior
to study entry are ineligible:
- Ischemic myocardial event, including angina requiring therapy and artery
revascularization procedures.
- - Ischemic cerebrovascular event, including transient ischemic attack (TIA) and
artery revascularization procedures.
- - Requirement for inotropic support (excluding digoxin) or serious (uncontrolled)
cardiac arrhythmia (including atrial flutter/fibrillation, ventricular
fibrillation or ventricular tachycardia)
- Placement of a pacemaker for control of rhythm.
- - New York Heart Association (NYHA) class III or IV heart failure.
- - Participants with known significant active cardiovascular or pulmonary disease at
the time of study entry are ineligible.
- - Participants receiving therapeutic agents known to prolong QT interval will be
excluded.
Patients on sertraline which has the conditional risk of prolonging the QT
interval will be allowed on study if they hold sertraline on the day of ONC201
administration.
- - Participants using concomitant CYP3A4/5 inhibitors within 72 hours prior to starting
study drug administration are ineligible.
- - Participants with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements, are ineligible.
- - Pregnant women are excluded from this study because there is unknown risk of ONC201
on the fetus.
Because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother on ONC201, breastfeeding should
be discontinued if the mother is treated with ONC201
