Gemcitabine in Newly-Diagnosed Diffuse Intrinsic Pontine Glioma

NCT02992015 | Completed Early Phase 1 DMC

• 1 other identifier: 15-1621.cc
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Diffuse Intrinsic Pontine Glioma (DIPG) is an aggressive childhood brain tumor that, despite many past clinical trials, has never been shown to respond to chemotherapy. Radiation therapy (RT) is effective in extending life but is not curative; median overall survival is 11 months. It is still unclear why the hundreds of clinical trials involving chemotherapy of DIPG have failed to demonstrate any activity against the tumor. Given that many agents tried in clinical trials cross the blood brain barrier (BBB), it is possible that there are factors specific to DIPG and its location that prevent adequate drug penetration. Gemcitabine has been selected for this study because there is strong evidence of DIPG cell line inhibition in vitro and good BBB penetration. Furthermore, pediatric dosing and toxicity has been established in prior studies of children with relapsed solid tumors and leukemia. The primary aim of this study is to determine the presence of gemcitabine in childhood DIPG tissue after systemic treatment with the drug. The secondary aim is to quantify the intratumoral gemcitabine concentration after systemic treatment. Participants in this study will be given a one time IV dose of gemcitabine prior to having standard of care surgery. During surgery biopsies will be obtained for clinical and research purposes along with a blood sample. Because patients will be undergoing this biopsy as part of their standard of care therapy here at Children's Hospital Colorado, this is an optimal time to obtain a tumor biopsy for this study. The biopsy will serve to see if the study drug is penetrating the tumor. Patients will then enter a follow-up period for 30 days post surgery.

Conditions

Diffuse Intrinsic Pontine Glioma

Outcome Measures

Primary Outcomes (1)

• PK testing levels of gemcitabine, its metabolite difluorodeoxyuridine (dFdU), and gemcitabine necleotides in peripheral blood and DIPG tissue

  The investigators will use liquid chromatography/tandem mass spectrometry (LC-MS/MS). An API 4000 instrument will be used, which has an approximate sensitivity of 0.1 ng/mg. Given the dimensions of the biopsy needle used, 10 mm length and 0.75 mm diameter, the investigators expect that each core will have an approximate volume of 4.5 mm2, which translates to a likely mass of 4.5 mg. Given that approximately 10 mg of tumor tissue has been necessary for quantification of gemcitabine and its matabolites in past studies, multiple cores of the six available for quantification from neighboring regions of the tumor may be combined; whenever possible. However, more than one separate measurement of concentrations will be done for each patient to determine any variation in concentrations across the tumor. An internal control measurement for gemcitabine will be determined using a variant gemcitabine compound enriched with 13C (Carbon 13).

  2-12 hours post systemic admininstration of gemcitabine.

Study Arms (1)

Gemcitabine

EXPERIMENTAL

The entire therapy on this study is one dose of gemcitabine. No intrapatient dose modifications are necessary. Gemcitabine will be given at 2100 mg/m2 IV over 30 minutes within 4 hours of planned surgical procedure.

Drug: Gemcitabine

Interventions

Gemcitabine DRUG

Participants receive a one time IV dose of gemcitabine prior to having standard of care surgery.

Also known as: Gemzar

Gemcitabine

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Children's Hospital Colorado: collaborator

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Adam Green, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 14, 2016
• Study Start: September 23, 2016
• Primary Completion: February 28, 2018
• Study Completion: March 6, 2024
• Last Updated: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)