| Eligibility |
Inclusion Criteria:
- Adults = 18 years of age
- Histologically and/or genomically documented recurrent or progressive astrocytoma,
IDH-mutant, grade 3 or 4 (diagnosis established by the presence of an IDH1 or IDH2
mutation along with grade 3 or 4 radiographic findings)
- Interval of at least 12 weeks from completion of adjuvant radiotherapy for gliomas to
dosing, or surgical confirmation of recurrent disease
- Performance status measured via Karnofsky Performance Score of = 60
- Confirmed measurable disease per response assessment in neuro-oncology criteria (RANO)
- Participants should have at least one 1.5cm x 1.5cm region of enhancing and
non-enhancing tumor within the surgically accessible region
- Ability of neurosurgeon to resect tumor
- Laboratory values at the Screening Visit:
- ANC count =1,500/mm3;
- Platelets =150,000/mm3;
- Hemoglobin > 9g/dL
- Total bilirubin =1.5 × the upper limit of normal (ULN) (subjects with Gilbert's
Syndrome are allowed if direct bilirubin is within normal limits)
- Aspartate aminotransferase (AST [SGOT]) =3× the ULN
- Alanine aminotransferase (ALT [SGPT]) =3 × the ULN
- Serum creatinine =1.5 mg/dL or a calculated creatinine clearance =60 mL/min
- Negative serum B-hCG test in women of childbearing potential (defined as women
=50 years of age, or >50 years of age with a history of amenorrhea for =12 months
prior to study entry)
- All men, as well as women of child-bearing potential must agree to use dual
contraceptive methods (hormonal or barrier method of birth control; abstinence) while
on the study drug and for 3 months afterward. Men must also refrain from sperm
donation for 4 months after treatment with BAY 2402234. Should a woman become pregnant
or suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
- A female of child-bearing potential is any woman (regardless of sexual orientation,
marital status, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
- Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
- Patients under age 18 (due to fundamental difference between pediatric and adult
gliomas)
- Treatment with an IDH inhibitor within 90 days of enrollment
- Treatment with temozolomide less than 23 days from study initiation, treatment with
CCNU or BCNU less than 42 days from study initiation, or treatment with any
cancer-directed systemic therapy less than 4 weeks or 5 half-lives from study
initiation, whichever is shorter
- Any immunomodulatory drug or molecularly targeted, monoclonal antibody, within 14 days
prior to initiation of study drug
- Use of any investigational agents within 28 days of baseline or 5 half-lives from
study initiation, whichever is shorter
- Increasing corticosteroid requirement or a dose of >24mg per day of dexamethasone or
an equivalent dose of other corticosteroids for longer than 48 hours within 7 days
prior to study initiation
- Radiotherapy within 12 weeks prior to registration unless surgical confirmation of
recurrent disease
- Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of
alopecia or lymphopenia, that has not resolved to = Grade 1, as determined by National
Cancer Institute CTCAE v5.0
- Major surgery within 28 days prior to initiation of study drug
- Active or clinically unstable bacterial, viral, or fungal infection requiring systemic
therapy
- Known human immunodeficiency virus or acquired immunodeficiency syndrome-related
illness
- Any of the following within 6 months prior to initiation of study drug: uncontrolled
congestive heart failure (New York Heart Association Classification 3 or 4), angina,
myocardial infarction, cerebrovascular accident, coronary or peripheral artery bypass
graft surgery, transient ischemic attack
- Pulmonary embolism within 1 month prior to initiation of study drug
- Unstable cardiac dysrhythmias or persistent prolongation of the QTc interval to >450
msec for males or >470 msec for females
- Any contraindication to contrast-enhanced MRI examination
- Evidence of clinically significant intracranial hemorrhage
- Previous history of an additional emergency, except for non-squamous-cell carcinoma of
skin or carcinoma-in-situ of the uterine cervix, unless the tumor was treated with
curative intent more than 2 years prior to study entry
- Requires anti-seizure medications that are known to be strong inducers of CYP3A4/5
enzymes (carbamazepine, phenobarbital, phenytoin). Strong inhibitors and/or strong
inducers of CYP3A4 should not be administered within 14 days or 5 half-lives
(whichever is shorter) of the start of BAY 2402234 treatment, or during BAY 2402234
treatment, unless there is an emergent or life-threatening medical condition
- Pregnant or lactating female
- Any severe, acute, or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, may interfere with the informed consent process and/or with
compliance with the requirements of the study, or may interfere with the
interpretation of study results and, in the Investigator's opinion, would make the
subject inappropriate for entry into this study
- Difficulty swallowing or malabsorption syndrome; refractory nausea & vomiting, chronic
gastrointestinal disease or previous significant bowel resection with clinically
significant sequelae that would preclude adequate absorption of study drug
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