Gemcitabine in Newly-Diagnosed Diffuse Intrinsic Pontine Glioma

Inclusion criteria

• Age greater than or equal to 3 years and less than 18 years at the time of enrollment
• Patients must meet both of the following:

• Clinical findings consistent with a presumed new diagnosis of DIPG
• Brain MRI findings consistent with a new diagnosis of DIPG in the opinion of the treating pediatric neuro-oncologist and neurosurgeon
• Organ Function Requirements

Adequate bone marrow function defined as:

• Platelet count ≥100,000/µl (no platelet transfusion for more than 3 days)
• Hemoglobin >8 g/dl and absolute neutrophil count (ANC) ≥1,000/µl

Adequate coagulation defined as:

• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ upper limit of normal (ULN) for age.

Adequate renal function defined as:

• Creatinine clearane or radioisotope GFR > 70 ml/min/1.73 m2 or
• Maximum serum creatinine (mg/dL) based on age/gender as follows:

• Male 3 to <6 yrs: 0.8 mg/dL
• Female 3 to <6 yrs: 0.8 mg/dL
• Male 6 to <10 yrs: 1.0 mg/dL
• Female 6 to <10 yrs: 1.0 mg/dL
• Male 10 to <13 yrs : 1.2 mg/dL
• Female 10 to <13 yrs: 1.2 mg/dL
• Male 13 to <16 yrs: 1.5 mg/dL
• Female 13 to <16 yrs: 1.4 mg/dL
• Male 16 to <18 yrs : 1.7 mg/dL
• Female 16 to <18 yrs: 1.4 mg/dL

The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.

Adequate liver function defined as:

• Total bilirubin <3x ULN for age and SGOT (AST) and SGPT (ALT) <2.5x ULN for age
• Patients must meet one of the following performance scores:

• ECOG performance status scores of 0, 1, or 2;
• Karnofsky score of ≥ 60 for patients > 16 years of age; or
• Lansky score of ≥ 60 for patients ≤ 16 years of age
• Pontine tumor biopsy is planned for the clinical care of the patient independent of study participation by the treating pediatric neurosurgeon and neuro-oncologist.
• Informed consent and assent obtained as appropriate.

Exclusion criteria

• Pregnant or breastfeeding patients due to teratogenic effects seen in animal/human studies.
• Patients who have received any tumor-directed therapy prior to biopsy. Concurrent treatment with corticosteroids is allowed.
• Patients with intratumoral hemorrhage larger than 0.5 cm on preoperative imaging.
• Patients with personal or family history of bleeding disorders.
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.