Inclusion criteria:
1. Be willing and able to provide written informed consent for the trial. Participants
with cognitive impairment will be enrolled. Cognitive function will be assessed by the
treating physician or designee through a neurological examination. The formal consent
for such participants will be obtained from their legally authorized representative.
2. Be 18 years of age or older on day of signing informed consent.
3. Have the following combined histological and molecular criteria:
1. Cohort 1: World Health Organization recurrent grade 1, 2, 3 glioma and NF1
mutation (somatic and/or germline). NF1 mutation identified from prior tumor
resection or from normal tissue samples (any CLIA certified NGS).
2. Cohort 2: World Health Organization recurrent grade 2, 3 OD (IDH mutated, 1p19q
codeleted)
4. Have had the following treatments:
1. Cohort 1: prior resection or biopsy with confirmed diagnosis of glioma per above.
Patient must have had prior radiation or chemotherapy for the treatment of
glioma.
2. Cohort 2: prior resection or biopsy with confirmed diagnosis of OD per above.
Patient must have had prior radiation or chemotherapy for the treatment of OD.
5. Have the following imaging and surgical criteria:
a. Progressive disease per RANO low-grade glioma or high-grade glioma criteria
depending on tumor grade AND presence of non-enhancing respectable tumor are required.
In cases that both non-enhancing and enhancing disease are present, collection of
non-enhancing disease separate from enhancing disease should be deemed possible per
the treating neurosurgeon.
6. Patients having undergone radiation are eligible as long as they are at least 12 weeks
from radiation with evidence of disease progression per advanced brain tumor imaging
[(ABTI); includes spectroscopy and perfusion MR studies] or biopsy.
7. Any number of prior relapses.
8. Be willing to provide tissue from an archival tissue sample.
9. Presence of archival tissue sample of at least 1 H&E and 10 unstained slides. One
tissue block will be requested but 10 unstained slides are acceptable if tissue block
is not available.
10. Have a performance status of ≥ 60 on the KPS.
11. If patient is on steroids, patient must be on a stable or decreasing dose of steroids
one week prior to screening MRI. Patients cannot be on more than 16mg of dexamethasone
or equivalent per day.
12. Demonstrate adequate organ function as defined in below Table. All screening labs
should be performed within 14 days (+3 working days) of treatment initiation.
Organ System Laboratory Value:
Hematological Absolute neutrophil count (ANC) ≥ 1,500 /mcL Platelets ≥ 100,000 /mcL
Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L Renal Serum creatinine OR Measured or calculateda
creatinine clearance (GFR can also be used in place of creatinine or CrCl)
≤1.5 X upper limit of normal (ULN) OR. ≥ 50 mL/min for patient with creatinine levels > 1.5 X institutional ULN Cardiac LVEF
≥ 50% Hepatic Serum total bilirubin ≤ 1.5 X ULN OR. 13. Female patients of childbearing potential should have a negative serum pregnancy test
within 14 days (+ 3 working days) of study enrollment.
14. Male and female patients of childbearing potential agree to use highly effective
contraception throughout the study and at least 90 days after the last study treatment
administration. 15. Male patients should agree to use an adequate method of contraception during the
course of the study and for 90 days after the last dose of the study drug.
Exclusion criteria:
1. Treatment with bevacizumab less than 6 months since enrollment.
2. Tumor localized primarily to spinal cord.
3. Presence of implanted chemotherapy. Previously resected implanted chemotherapy is not
excluded.
4. Less than 12 weeks from completing radiotherapy. Patients with proven progressive
disease by biopsy or partial resection or with new lesions outside of the radiation
field should not be excluded even if they are within 12 weeks of radiation.
5. Patient currently participating in a study of an investigational agent or using an
investigational device for therapeutic purposes.
Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN AST (SGOT)
and ALT (SGPT) ≤ 3.0 X ULN Coagulation International Normalized Ratio (INR) or
Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT)
≤1.5 X ULN a Creatinine clearance should be calculated per institutional standard.
6. Patient has a known history of Human Immunodeficiency Virus (HIV) (positive HIV 1/2
antibodies); HTLV1 and/or HTLV2; active Hepatitis B (e.g., HBsAg reactive) or
Hepatitis C (e.g., HCV RNA [qualitative] is detected). Patients with prior HBV
vaccination (anti-HBs positive, HBsAg negative, anti-HBc negative) will NOT be
excluded.
7. Patient has a diagnosis of immunodeficiency or is receiving systemic immunosuppressive
therapy (except for steroids) within 7 days of study entrance.
8. Patient has had prior chemotherapy or targeted small molecule therapy, within 3 weeks
prior to study Day 1, or has not recovered (i.e., ≤ Grade 1 or at baseline) from
adverse events due to a previously administered agent.
1. Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and
may qualify for the study.
2. Note: If patient received major surgery (other than craniotomy), they must have
recovered adequately from the toxicity and/or complications from the intervention
prior to starting therapy.
9. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or in situ cervical cancer that has undergone potentially curative therapy.
10. Has an active infection requiring systemic therapy.
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient to participate, in the opinion of the treating investigator.
12. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
13. Is pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit.
14. Has contraindication for undergoing MRIs.
15. Is not a candidate for non-emergent surgical resection.
16. Is taking prohibited concomitant medications (Appendix 5) and is unable to discontinue
these medications prior to study enrollment.
17. A history or current evidence/risk of retinal vein occlusion or central serous
retinopathy
