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|NCT03452930 : EDO-S101 for MGMT Unmethylated Glioblastoma (nGBM)|
|Ages||Min: 18 Years Max: N/A|
1. Be willing and able to provide written informed consent for the trial.
2. Be >/= 18 years of age on day of signing informed consent.
3. Have histologically confirmed World Health Organization Grade IV glioma (GB or
4. Confirmed MGMT-promoter unmethylated status and IDH wildtype. The presence of an IDH
mutation will be an exclusionary criteria for trial enrollment.
5. Have a performance status of >/= 60 on the Karnofsky Performance Scale (KPS).
6. If patient is on steroids, patient must be on a stable or decreasing dose of steroids
for at least 5 days at the time of baseline brain MRI.
7. Demonstrate adequate organ function. All screening labs should be performed within 14
days (+3 working days) of treatment initiation. Absolute neutrophil count (ANC) >/=
1,500 /mcL; Platelets >/= 100,000 /mcL; Hemoglobin >/= 9 g/dL or >/= 5.6 mmol/L; Serum
creatinine OR Measured or calculated creatinine clearance (GFR can also be used in
place of creatinine or CrCl) = 1.5 X upper limit of normal (ULN) OR >/= 60 mL/min
for subject with creatinine levels > 1.5 X institutional ULN; Serum total bilirubin
= 1.5 X ULN OR Direct bilirubin = ULN for subjects with total bilirubin levels >
1.5 ULN; AST (SGOT) and ALT (SGPT) = 2.5 X ULN; International Normalized Ratio (INR)
or Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT) = 1.5 X ULN.
8. Female subjects of childbearing potential should have a negative serum pregnancy test
within 72 hours of starting first dose of study drug.
9. Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the
duration of the study. Subjects of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for > 1 year.
10. Male subjects should agree to use an adequate method of contraception during the
course of the study.
11. Patients must have completed standard radiation therapy with concurrent TMZ and must
not have evidence of progressive disease on post treatment imaging. Progression can
only be defined using diagnostic imaging if there is new enhancement outside of the
radiation field (beyond the high-dose region or 80% isodose line) or if there is
unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor
areas [i.e, > 70% tumor cell nuclei in areas], high or progressive increase in MIB-1
proliferation index compared with prior biopsy, or evidence for histologic progression
or increased anaplasia in tumor). Note: Given the difficulty of differentiating true
progression from pseudoprogression, clinical decline alone, in the absence of
radiographic or histologic confirmation of progression, will not be sufficient for
definition of progressive disease in the first 12 weeks after completion of concurrent
chemoradiotherapy. (For Stage 1: Post-chemoradiation group only)
12. Patients must have undergone surgery of their GBM, and must not have had any further
treatment following surgery. A minimal interval of 7 days between the day of surgery
and the day of inclusion should be respected; a maximal interval of 31 days between
the day of surgery and the day of inclusion should be respected; the patient should
have fully clinically recovered from the surgery. (For Stage 2: Radiation with
concurrent and adjuvant EDO-S101 only)
13. Patients must undergo surgery and must not have further treatment. (For MTD Expansion
1. Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics
delivered by local injection or convection enhanced delivery. Prior treatment with
Gliadel® wafers will be excluded. Concomitant use of the Optune device will also be
2. Is currently participating or has participated in any other investigational or
therapeutic trial before or after chemoradiation.
3. Any serious medical condition that interferes with adherence to study procedures.
4. Has had prior chemotherapy, targeted small molecule therapy, within 2 weeks prior to
study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse
events due to a previously administered agent. Note: Subjects with = Grade 2
neuropathy are an exception to this criterion and may qualify for the study. Note: If
subject received major surgery, they must have recovered adequately from the toxicity
and/or complications from the intervention prior to starting therapy. ( For Stage 1:
Post-chemoradiation group only)
5. Patients with a history of a second malignancy diagnosed within three (3) years of
study enrollment or have 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
6. New York Heart Association (NYHA) stage III/IV congestive heart failure, arrhythmias
not adequately controlled.
7. Patients with prolonged QTc interval defined as male >450 msec and female > 470 msec.
8. Patients who are on treatment with drugs known to prolong the QT/QTc interval.
9. Has known gliomatous meningitis, extracranial disease, or multifocal disease.
10. Has an active infection requiring systemic therapy.
11. Has an ongoing or previous history of spontaneous intratumoral hemorrhage.
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit.
15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Testing not required.
16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected). (Testing not required for Stage 2 and MTD Expansion
17. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
18. Contraindication for undergoing MRIs
19. Use of any drug with HDAC inhibiting activity.
20. Use of valproate in any of its indications (epilepsy, mood disorder). Valproate, due
to its HDAC inhibiting activity is contraindicated. For those patients on valproate,
valproate will need to be discontinued and switched to a different anti-epileptic
agent or psychotropic agent. A washout period of 4 days from valproate acid will be
allowed prior to enrolling into the trial.
21. Has had any prior chemotherapy, targeted small molecule therapy. (For Stage 2:
Radiation with concurrent and adjuvant EDO-S101 and MTD Expansion cohort only)
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