Gemcitabine in Newly-Diagnosed Diffuse Midline Glioma

An Early Phase 1 Trial of Gemcitabine in Newly-Diagnosed Diffuse Midline Glioma

The primary aim of this study is to determine the presence of gemcitabine in childhood diffuse midline gliomas (DMG) (previously classified as diffuse intrinsic pontine glioma [DIPG]) after systemic treatment with the drug.

Study Overview

• Status: Withdrawn
• Conditions: Glioma; Diffuse Intrinsic Pontine Glioma; Glial Tumor of Brain
• Intervention / Treatment: Drug: Gemcitabine; Procedure: Tumor biopsy and blood draw

Detailed Description

Participants in this study will be given a one-time, intravenous (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. Cerebrospinal Fluid (CSF) is optional and will only be obtained if clinically indicated. This will be determined by the investigators and the provider performing the procedure.

Because patients will be undergoing a biopsy/resection as part of their standard-of-care therapy, 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.

This trial is in conjunction with a University of Colorado trial started in 2016, "Gemcitabine in Children With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma" (NCT02992015).

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • The University of Michigan Rogel Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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 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
• Adequate bone marrow, liver, renal and metabolic function (per protocol)
• Adequate coagulation defined as Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ upper limit of normal (ULN ) for age

• Patients must meet one of the following performance scores:

  • ECOG performance status scores of 0, 1, or 2; 8
  • 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 due to teratogenic effects seen in animal/human studies
• 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.
• Patients with known hypersensitivity to gemcitabine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine; Gemcitabine will be given at 2100 mg/m2 IV over 30 minutes within 4 hours of planned surgical procedure. The surgical procedure is standard of care.	Drug: Gemcitabine; Participants receive a one time IV dose of gemcitabine prior to having standard of care surgery.; Other Names: Gemzar; Procedure: Tumor biopsy and blood draw; As part of standard of care, all participants will undergo tumor biopsy and collection of peripheral blood.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with detectable intratumoral gemcitabine after systemic treatment with the drug	Gemcitabine will be considered to be detectable in a participant's tumor sample if gemcitabine or one of its metabolites (difluorodeoxyuridine [dFdU] or gemcitabine triphosphate [dFdCTP]) is detected at a measurable level in any of the participant's tumor samples. Undetectable gemcitabine will be defined as gemcitabine, dFdU, and dFdCTP levels below the detectable limits for all of an individual participant's samples, in the setting of detectable gemcitabine, dFdU, or dFdCTP in the plasma and/or cerebrospinal fluid (CSF) for that patient, and the pathologic review showing viable tumor tissue.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of gemcitabine in patient tumor sample	Gemcitabine, dFdU and dFdCTP will be quantified in the available tumor sample(s), in plasma, and in CSF (if available). For this pilot trial, gemcitabine PK results will be analyzed descriptively, and this trial is not designed for statistical analysis.	Day 1

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: University of Colorado, Denver
• Investigators: Principal Investigator: Carl Koschmann, M.D., University of Michigan

Study record dates

Study Major Dates

• Study Start (Anticipated): November 30, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 7, 2019
• First Posted (Actual): August 9, 2019

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 25, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Glioma
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Stem Neoplasms; Infratentorial Neoplasms; Glioma; Diffuse Intrinsic Pontine Glioma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: UMCC 2018.159; HUM00135182 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No