Gemcitabine in Newly-Diagnosed Diffuse Intrinsic Pontine Glioma
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|ClinicalTrials.gov Identifier: NCT02992015|
Recruitment Status : Suspended (Patient Safety Review by DSMC)
First Posted : December 14, 2016
Last Update Posted : July 19, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Intrinsic Pontine Glioma||Drug: Gemcitabine||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||A Clinical Trial Trial of Gemcitabine in Children With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)|
|Actual Study Start Date :||September 2016|
|Estimated Primary Completion Date :||September 2018|
|Estimated Study Completion Date :||December 2018|
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.
Participants receive a one time IV dose of gemcitabine prior to having standard of care surgery.
Other Name: Gemzar
- PK testing levels of gemcitabine, its metabolite difluorodeoxyuridine (dFdU), and gemcitabine necleotides in peripheral blood and DIPG tissue [ Time Frame: 2-12 hours post systemic admininstration of gemcitabine. ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02992015
|United States, Colorado|
|Children's Hospital Colorado|
|Aurora, Colorado, United States, 80045|
|Principal Investigator:||Adam Green, MD||University of Colorado, Denver|