Gemcitabine Hydrochloride in Treating Patients with Diffuse Midline Glioma

This early phase I trial studies how well gemcitabine hydrochloride works in treating patients with diffuse midline glioma. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Inclusion Criteria

• Patients must meet both of the first two conditions, OR the third: * Clinical findings consistent with a presumed new diagnosis of diffuse midline glioma (DMG) in the opinion of the treating neuro-oncologist, AND * Brain magnetic resonance imaging (MRI) findings consistent with a new diagnosis of DMG based on multidisciplinary consensus after review of imaging * OR, recurrent DMG requiring tumor resection or biopsy
• Platelet count >= 100,000/ul (no platelet transfusion for more than 3 days)
• Hemoglobin > 8 g/dl
• Absolute neutrophil count (ANC) >= 1,000/ul
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< upper limit of normal (ULN) for age
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows: maximum serum creatinine (mg/dL) * 3 to < 6 years: 0.8 (male and female) * 6 to < 10 years: 1 (male and female) * 10 to < 13 years: 1.2 (male and female) * 13 to < 16 years: 1.5 (male) 1.4 (female) * 16 to < 18 years: 1.7 (male) 1.4 (female)
• Total bilirubin < 3 x ULN for age
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x ULN for age
• Patients must meet one of the following performance scores: * Eastern Cooperative Oncology Group (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
• DMG biopsy/resection 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 are not eligible
• Patients who have received any tumor-directed therapy prior to biopsy are not eligible; concurrent treatment with corticosteroids is allowed
• Any tumor-specific or clinical features that make surgical intervention unsafe in the opinion of the treating neurosurgeon
• Patients with personal or family history of bleeding disorders are not eligible
• 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 are not eligible

PRIMARY OBJECTIVES:

I. To measure the concentration of gemcitabine hydrochloride (gemcitabine) and its metabolites in patient biopsy-derived diffuse midline glioma tissue after pre-biopsy treatment and to compare these concentrations to historical control levels achieved in adult glioblastoma (GBM) tissue and to know in vitro inhibitory drug concentrations for diffuse midline gliomas, cell lines (previously classified as diffuse intrinsic pontine glioma (DIPG).

OUTLINE:

Within 4 hours of standard of care surgery, patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes.

After completion of study treatment, patients are followed up for 30 days.

Lead Organization
Children's Hospital Colorado

Principal Investigator
Adam L. Green

Primary ID 15-1621
Secondary IDs NCI-2017-01650
Clinicaltrials.gov ID NCT02992015