Phase
Condition
Neoplasms
Brain Tumor
Cancer/tumors
Treatment
NEO100
Clinical Study ID
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Patient must have radiographically confirmed, newly diagnosed or recurrentpediatric-type high grade glioma: Diffuse Midline Glioma, H3 K27-altered; Diffusehemispheric glioma, H3 G34-mutant, Diffuse pediatric-type HGG, grade III and IVH3-wildtype and IDH-wildtype with imaging and/or pathology consistent with a DMG, (including spinal cord tumors); or Recurrent malignant tumors involving thebrainstem or posterior fossa (choroid plexus carcinoma, CNS embryonal tumors, andpineoblastoma).
Karnofsky ≥ 50 for patients > 16 years of age or Lansky ≥ 50 for patients ≤ 16 yearsof age. Participants who are unable to walk because of paralysis, but who are up ina wheelchair, will be considered ambulatory for the purpose of assessing theperformance score.
If clinically indicated, participants must be willing to provide adequate tissue forPK analysis, either from a surgical biopsy or needle biopsy.
Aged ≥5 to ≤18 years.
Patients recurrent or progressive disease must have recovered from all acute sideeffects of prior therapy.
From the projected start of scheduled study treatment, the following time periodsmust have elapsed: At least 7 days after last dose of a biologic agent or beyondtime during which adverse events are known to occur for a biologic agent, 5half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.
Prior use of temozolomide during radiation at maximum of the standard pediatricdosing (defined as 90 mg/m2 /dose continuously during radiation therapy for 42 days)or dexamethasone is allowed.
Corticosteroids: Patients who are receiving dexamethasone must be on a stable ordecreasing dose for at least 3 days prior to baseline magnetic resonance imaging (MRI) scan.
Surgical Resection: Patients may not have had a surgical resection within four weeksof starting NEO100 and any post-surgical complications must have resolved prior toinitiation of NEO100.
Radiation Therapy: Patients may not receive radiation therapy within four weeks ofstarting NEO100. Patients may not be enrolled if they require radiation therapyduring Cycle 1 (the DLT Period). Patients may have SOC radiation therapy in Cycle 2or beyond but will require a second DLT evaluation period to participate.
Peripheral absolute neutrophil count (ANC) ≥ 1000/mm^3 (1.0g/l) AND
Platelet count ≥ 100,000/mm^3 (100x10^9/l) (transfusion independent, defined as notreceiving platelet transfusions for at least 7 days prior to enrollment).
Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70mL/min/1.73 m^2.
Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) forage.
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase (ALT)) ≤ 2 xULN.
Serum albumin ≥ 2 g/dL.
No or mild renal impairment (i.e., 60 mL/min or 1.73m2 with Schwartz equation).
No evidence of dyspnea at rest, no exercise intolerance due to pulmonaryinsufficiency, and a pulse oximetry of > 92% while breathing room air.
Participants with seizure disorder may be enrolled if seizure disorder is wellcontrolled.
The effects of the study drugs on the developing human fetus are unknown. For thisreason, females of child-bearing potential and males must agree to use adequatecontraception. Adequate methods include: hormonal or barrier method of birthcontrol; or abstinence prior to study entry and for the duration of studyparticipation. Should a woman become pregnant or suspect she is pregnant while sheor her partner is participating in this study, she should inform her treatingphysician immediately. Males treated or enrolled on this protocol must also agree touse adequate contraception prior to the study and for the duration of studyparticipation.
A legal parent/guardian and patient must be able to understand, and willing to sign,a written informed consent (parental permission) or assent document, as appropriate.
Exclusion
Exclusion Criteria:
Diagnosis of any pediatric-type glioma not described in inclusion criteria.
Participants who are currently receiving another investigational drug.Investigational imaging agents or agents used to enhance tumor visibility on imagingor during tumor biopsy/resection should be discussed with the Medical Monitors.
Participants who are currently receiving other anti-cancer agents.
Participants with a known disorder that affects their immune system, such as humanimmunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorderrequiring systemic cytotoxic or immunosuppressive therapy. Note: Participants thatare currently using inhaled, intranasal, ocular, topical or other non-oral ornon-intravenous (IV) steroids are not necessarily excluded from the study but needto be discussed with the Medical Monitor.
A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of aQTc interval >450 milliseconds (ms).
A history of additional risk factors for TdP (e.g., heart failure, hypokalemia,family history of Long QT Syndrome), or the use of concomitant medications thatprolong the QT/QTc interval.
Participants with uncontrolled infection or other uncontrolled systemic illness.
Female patients of childbearing potential must not be pregnant or breast-feeding.Female patients of childbearing potential must have a negative serum or urinepregnancy test prior to the start of therapy (as clinically indicated).
Active illicit drug use or diagnosis of alcoholism.
History of allergic reactions attributed to compounds of similar chemical orbiologic composition as the agents used in study.
Evidence of disseminated disease, including diffuse leptomeningeal disease orevidence of CSF dissemination as determined based upon available clinical detailsand not a study required MRI study or CSF test.
Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.
Concomitant use of potent CYP3A4/5 inhibitors during the treatment phase of thestudy and within 72 hours prior to starting study drug administration.
Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducingantiepileptic drugs (EIAEDs), during the treatment phase of the study and within 2weeks prior to starting treatment. Concurrent corticosteroids are allowed.