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Gemcitabine in Newly-Diagnosed Diffuse Midline Glioma

Primary Purpose

Glial Tumor of Brain, Diffuse Intrinsic Pontine Glioma, Glioma

Status

Withdrawn

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Gemcitabine

Tumor biopsy and blood draw

About this trial

This is an interventional basic science trial for Glial Tumor of Brain focused on measuring Glioma

Eligibility Criteria

3 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The University of Michigan Rogel Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gemcitabine

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT04051047

First Posted

August 7, 2019

Last Updated

November 25, 2019

Sponsor

University of Michigan Rogel Cancer Center

Collaborators

University of Colorado, Denver

1. Study Identification

Unique Protocol Identification Number

NCT04051047

Brief Title

Gemcitabine in Newly-Diagnosed Diffuse Midline Glioma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Withdrawn

Why Stopped

Withdrawn by Principal Investigator

Study Start Date

November 30, 2019 (Anticipated)

Primary Completion Date

December 2021 (Anticipated)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

Collaborators

University of Colorado, Denver

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glial Tumor of Brain, Diffuse Intrinsic Pontine Glioma, Glioma

Keywords

Glioma

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Gemcitabine

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemzar

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Tumor biopsy and blood draw

Intervention Description

As part of standard of care, all participants will undergo tumor biopsy and collection of peripheral blood.

Primary Outcome Measure Information:

Title

Number of participants with detectable intratumoral gemcitabine after systemic treatment with the drug

Description

Time Frame

Day 1

Secondary Outcome Measure Information:

Title

Concentration of gemcitabine in patient tumor sample

Description

Time Frame

Day 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carl Koschmann, M.D.

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Michigan Rogel Cancer Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Gemcitabine in Newly-Diagnosed Diffuse Midline Glioma

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