Inclusion Criteria:
Each subject must meet the following criteria:
1. Provide signed, written informed consent prior to the initiation of any study-specific
procedures (consent from guardians for minor children and patient assent according to
institution and Institutional Review Board (IRB) standards)
2. Age ≥ 1 year of age and ≤ 30 years of age at the time of study entry. 3. Have radiographically suspected or histologically confirmed newly diagnosed DIPG or
DMG with the following defining disease characteristics/features:
- - Part 1 and Part 2:
- DIPG: radiographic imaging showing a diffuse expansion of the brainstem/pons
by a tumor that is poorly defined but abnormally bright in signal on
T2-weighted images and abnormally dark on T1-weighted images; contrast
enhancement, when present, is typically mild; there may be some indication
of necrosis, and the basilar artery is commonly engulfed by tumor.
- - DMG: the same imaging characteristics as noted above for DIPG are present,
but the lesion can extend superiorly up into the midbrain and thalami,
and/or inferiorly to the medulla.
- - In cases of disease that is not classic for DIPG or DMG, biopsy may be
necessary in order to obtain histological confirmation of eligibility.
- - Part 2: newly-diagnosed DIPG or DMG planning to undergo biopsy at the
recommendation of the treating physician; to be considered evaluable for PK
tissue concentration analysis, tumor samples must have at least 50% viable tumor
cells with <30% necrosis or hemorrhage as determined by the study
neuropathologist.
4. If receiving glucocorticoid therapy: dexamethasone allowed with maximum allowable dose
16mg/day. 5. Have measurable or non-measurable disease per RANO criteria. 6. Have Lansky (age 1
- - 15) / Karnofsky (age ≥ 16) Performance Score of ≥ 50% or Eastern
Cooperative Oncology Group (ECOG) Performance Status (age ≥ 18) of 0 - 2.
- - Subjects unable to walk because of paralysis, but who can sit without
assistance/restraint and control a wheelchair, will be considered ambulatory for
the purpose of assessing the performance score.
7. Have acceptable liver function defined as:
- - Total serum bilirubin ≤ 1.5 x upper limit of normal for the study site (ULN) (in
subjects with known Gilbert Syndrome, total bilirubin ≤ 3 x ULN, with direct
bilirubin ≤ 1.5 x ULN)
- Aspartate Transaminase (AST), Serum Glutamic Oxaloacetic Transaminase (SGOT),
Alanine Transaminase (ALT), Serum Glutamic-Pyruvic Transamine (SGPT) ≤ 3 x ULN
(if liver metastases are present, then ≤ 5 x ULN is allowed)
- Serum albumin ≥ 3 grams/deciliter (g/dL)
8.
Have acceptable renal function defined as:
- - Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥70
milliliters (mL)/min/1.73 meters squared (m2) or a serum creatinine based on
age/gender as follows: 1 to < 2 years: 0.6 (male); 0.6 (female) 2 to < 6 years:
0.8 (male); 0.8 (female) 6 to < 10 years: 1 (male); 1 (female) 10 to < 13 years:
1.2 (male); 1.2 (female) 13 to < 16 years: 1.5 (male); 1.4 (female)
- 16 years: 1.7 (male);1.4 (female)
- Threshold creatinine values derived from the Schwartz formula for
estimating GFR utilizing child length and stature data published by the
Center for Disease Control (Schwartz 2009)
9.
Have acceptable bone marrow function defined as:
- - Absolute neutrophil count (ANC) ≥ 1,500 cells/ cubic millimeter (mm3)
- Platelet count ≥ 100,000 cells/mm3 (unsupported, no transfusion within 7 days of
enrollment)
- Hemoglobin > 9.0 g/dL (unsupported, no transfusion within 7 days of enrollment)
10.
Have acceptable coagulation parameters (anti-coagulation allowed) defined as:
- - International normalized ratio (INR) ≤ 2 x ULN unless on anticoagulation or
prothrombin time (PT) within normal limits.
- - Activated partial thromboplastin time (aPTT) within normal limits.
11. Have a negative serum pregnancy test result at screening (for females of child bearing
potential (FCBP); not applicable to subjects who are unable to become pregnant,
including those with tubal ligation, bilateral oophorectomy and/or hysterectomy,
post-menopausal is defined as > 12 months since last menstrual cycle)
12. FCBP and male subjects whose sexual partner(s) are FCBP must agree to abstain from
heterosexual activity or use a double barrier method of contraception (e.g., condom
and occlusive cap with spermicide) or highly effective contraception (intrauterine
device or system, established hormonal contraceptive methods on a stable dose from the
time of the last menstrual cycle, or vasectomized partner with confirmed azoospermia)
from the time of study entry to 1 month after the last day of treatment.
Exclusion Criteria:
Subjects must not meet any of the following criteria:
1. Have a concurrent or secondary malignancy. 2. Have a low-grade glioma (Grade II or less)
3. Have received prior treatment with radiation, chemotherapy, anti-neoplastic, or
investigational agents. 4. Have had major surgery other than a minor outpatient procedure within 28 days prior to
dose assignment or have not recovered from major side effects of the surgery if more
than 4 weeks have elapsed since surgery. 5. Have poorly controlled hypertension despite the use of antihypertensive agents defined
as blood pressure ≥95th percentile for age and weight or >160/90 on at least 2
repeated determinations on separate days within 2 weeks (14 days) prior to initiation
of screening. 6. Have a history of cardiac dysfunction including:
- - myocardial infarction within 6 months prior to initiation of screening.
- - history of documented congestive heart failure (New York Heart Association
functional classification III-IV) within 6 months prior to initiation of
screening.
- - electrocardiogram (ECG) with QTc >470 msec at screening.
- - echocardiogram with ejection fraction <50% or a decrease in the left ventricular
shortening fraction to <27%
7.
Have a known history of Human Immunodeficiency Virus (HIV) seropositivity. 8. Have active (acute or chronic) or uncontrolled severe infections. 9. Have active poor wound healing (delayed healing, wound infection or fistula)
10. Have evidence of active clinically significant bleed (e.g., gastrointestinal bleed,
hemoptysis, or gross hematuria) at screening. 11. Are pregnant or nursing, where pregnancy is defined as the state of a female after
conception and until the termination of gestation, confirmed by a positive serum human
chorionic gonadotropin (hCG) laboratory test. 12. Have a known sensitivity to any component of BXQ-350. 13. Have other concurrent severe and/or uncontrolled medical condition that would, in the
Principal Investigator's judgment contraindicate the subject's participation in the
clinical study or obscure assessment of toxicity
