Diffuse Intrinsic Pontine GliomaEarly Phase 1NCT02992015
Gemcitabine in Newly-Diagnosed Diffuse Intrinsic Pontine Glioma
A Early Phase 1 study testing Gemcitabine in people with Diffuse Intrinsic Pontine Glioma, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2016to 6 Mar 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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:
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- 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
- Male 6 to <10 yrs: 1.0 mg/dL
- Female 6 to <10 yrs: 1.0 mg/dL
- Male 10 to <13 yrs : 1.2 mg/dL
- Female 10 to <13 yrs: 1.2 mg/dL
- Male 13 to <16 yrs: 1.5 mg/dL
- Female 13 to <16 yrs: 1.4 mg/dL
- Male 16 to <18 yrs : 1.7 mg/dL
- Female 16 to <18 yrs: 1.4 mg/dL
- The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
- Adequate liver function defined as:
- Total bilirubin <3x ULN for age and SGOT (AST) and SGPT (ALT) <2.5x ULN for age
- Patients must meet one of the following performance scores:
- 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
- Pontine tumor biopsy 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Colorado
Aurora, Colorado, 80045
About this study
Official title: A Clinical Trial Trial of Gemcitabine in Children with Newly-Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)
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
- Being tested
- Gemcitabine
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemzar
Participants receive a one time IV dose of gemcitabine prior to having standard of care surgery.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 2-12 hours post systemic admininstration of gemcitabine.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2016 (estimated)
- Study start23 Sep 2016
- Primary completion28 Feb 2018
- Study completion6 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Intrinsic Pontine GliomaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Colorado
- Responsible party
- Sponsor
- Investigators
- Adam Green, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02992015
- Sponsor's protocol ID
- 15-1621.cc
- Status last verified
- Mar 2025
- First submitted
- 29 Nov 2016
- Last updated
- 7 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial Trial of Gemcitabine in Children with Newly-Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)
- ClinicalTrials.gov ID
- NCT02992015
- Acronym / sponsor ID
- 15-1621.cc
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Children's Hospital Colorado
- Study start
- 23 Sep 2016 (actual)
- Primary completion
- 28 Feb 2018 (actual)
- Study completion
- 6 Mar 2024 (actual)
- First posted
- 14 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine | Experimental | Drug: GemcitabineThe 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. |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (32 listed)
- 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:
- Organ Function Requirements
- The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
- Patients must meet one of the following performance scores:
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineAlso: GemzarParticipants receive a one time IV dose of gemcitabine prior to having standard of care surgery. | Drug | Gemcitabine |
Primary outcome
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Green, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Gemcitabine in people with Diffuse Intrinsic Pontine Glioma, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2025.