Diffuse Intrinsic Pontine GliomaPhase 1NCT03086616
CED With Irinotecan Liposome Injection Using Real Time Imaging in Children With Diffuse Intrinsic Pontine Glioma (DIPG) (PNOC 009)
A Phase 1 study testing Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI) in people with Diffuse Intrinsic Pontine Glioma, run by Sabine Mueller, MD, PhD at 1 site in United States.
Trial summary
This is a Phase I and Early Efficacy Study of Convection Enhanced Delivery (CED) of irinotecan liposome injection (nal-IRI) Using Real Time Imaging with Gadolinium in Children with Diffuse Intrinsic Pontine Glioma who have completed focal radiotherapy Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2017to 4 Oct 2021
- Phase
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with newly diagnosed DIPG by MRI; defined as patients with a pontine location and diffuse involvement of at least 2/3 of the pons are eligible without histologic diagnosis. For lesions with typical imaging features, biopsy is neither encouraged nor required for eligibility. Tumors that are biopsied will be eligible if proven to be supportive of the diagnosis of a DIPG. Consensus of diagnosis by the study team must be met.
- Treatment must begin at a minimum of 4 weeks after, but no later than 14 weeks after, the date of the completion of focal radiotherapy.
- Prior Chemotherapy: Patients should be at least 30 days from last chemotherapy dose prior to start of CED infusion, with exception of antibody half-lives. For antibody therapies, at least 3 half-lives of the antibody after last dose of monoclonal antibody should have passed prior to CED infusion. Patients less than 30 days from last chemotherapy dose should be discussed with the study chair(s).
- Prior Radiation: Patients must have completed prior treatment with standard focal radiotherapy as part of initial treatment for DIPG and had their last dose at least 4 weeks prior to and no later than 14 weeks from the first CED treatment. Patients beyond 14 weeks from radiation therapy but with stable disease should be discussed with the study chair.
- Age ≥ 2 years of age. Patients younger than 3 years of age may be enrolled on study at the discretion of the Study Chair(s) if supporting evidence that brainstem lesion represents a brainstem glioma.
- Karnofsky ≥ 50 for patients > 16 years of age and Lansky ≥ 50 for patients 16 years of age and younger. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
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- Life expectancy of greater than 12 weeks measured from the date of completion of radiotherapy.
- Corticosteroids: Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
- Organ Function Requirements
- Adequate Bone Marrow Function Defined as:Peripheral absolute neutrophil count (ANC) ≥1000/mm3 and platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) and normal coagulation defined as normal international normalized ratio (INR) or per institutional guidelines.
- Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 milliliters (mL)/min/1.73 m2 or
- A serum creatinine based on age/gender as follows:
- Age Maximum Serum Creatinine (mg/dL) Male Female 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
- ≥ 16 years 1.7 1.4
- Adequate Liver Function Defined as: Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper limit of normal (ULN) for age and serum glutamate pyruvate transaminase (SGPT) (ALT) less than or equal to 110 U/L. and Serum albumin ≥ 2 g/dL.
- Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.
- The effects of irinotecan liposome injection on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of irinotecan liposome injection administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate
Who cannot join
- Patients who had clinical and/or radiographic (MRI) progression of tumor following external beam radiation therapy.
- Patients with metastatic disease, including leptomeningeal or subarachnoid disseminated disease.
- Patients with tumor morphology or other imaging findings that predict poor coverage of the majority of the tumor including significant tumor volume outside the pons or presence of large cysts within the tumor that would prevent adequate tumor coverage by CED. Patients with concern for adequate tumor coverage based on tumor morphology should be discussed with the study chairs.
- Patients who are receiving any other tumor-directed therapy
- Patients with MRI or clinical evidence of uncontrolled tumor mass effect are excluded; the patients should be discussed with the study chair(s) and study neurosurgeon prior to any planned CED treatment.
- Untreated symptomatic hydrocephalus determined by treating physician.
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- Patients should not be on enzyme-inducing anticonvulsants or other drugs that might interact with the cytochrome P450 enzyme system. If previously on an enzyme-inducing anti-epileptic drug (EIAED), patients should be off for at least 10 days prior to CED infusion and discussed with the Study Chair.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, topotecan, gadolinium, or lipids.
- 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.
- Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 14 days of registration.
- Patients who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy. Telemedicine visits are acceptable.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94158
About this study
Official title: A Phase I and Early Efficacy Study of Convection Enhanced Delivery of Irinotecan Liposome Injection Using Real Time Imaging With Gadolinium in Children With Diffuse Intrinsic Pontine Glioma
This is a Phase I and Early Efficacy Study of Convection Enhanced Delivery (CED) of irinotecan liposome injection (nal-IRI) Using Real Time Imaging with Gadolinium in Children with Diffuse Intrinsic Pontine Glioma who have completed focal radiotherapy
Read the detailed description
This study will assess the safety and tolerability of repeated administration of nal-IRI co-infused with gadoteridol given by intratumoral CED in children with newly diagnosed DIPG.
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Being tested
- Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)
- Keywords
- DIPG, CED, glioma
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)Drug
Also called Irinotecan Liposome Injection
Nal-IRI will be given directly into the tumor using CED.
| Study group | Role | What they receive |
|---|---|---|
| Newly Diagnosed DIPG | Experimental | Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI): Nal-IRI given directly into the tumor using a method called CED to newly diagnosed DIPG subjects after completion of radiotherapy. CED will be performed every 4-8 weeks. Drug concentration will start at 20mg/ml and escalate up to 40 mg/ml concentration. Receives: Drug: Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Treatment-Related Adverse Events (AE)
Safety of repeated CED of nal-IRI following standard of care focal radiotherapy will be assessed by monitoring for adverse events, scheduled laboratory assessments, vital sign measurements, and physical examinations for subjects who receive the vaccination. The severity of toxicities will be graded according to the NCI CTCAE v4.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to study drug(s). Grade 1 and 2 adverse events will be summarized if related to study therapy. Descriptive statistics will be utilized to display the data on toxicity
Measured: 12 months
Secondary outcomes (1)
Overall Survival (OS) at 12 months (OS12)
Any eligible subject treated on the dose level that will be investigated within the expansion cohort will be considered evaluable for clinical efficacy. Analyses will be performed after all enrolled patients have completed 12 months, or whenever the status of all patients has been established, whichever comes first. The primary analysis will be based on the Kaplan-Meier method. Kaplan-Meier estimates and the associated 95% confidence intervals (CI) will be calculated
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2017
- Study start31 Oct 2017
- Primary completion4 Oct 2021
- Study completion4 Oct 2021
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.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sabine Mueller, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- The V Foundation for Cancer Research, Pacific Pediatric Neuro-Oncology Consortium
- Responsible party
- Sponsor-investigator, Sabine Mueller, MD, PhD, University of California, San Francisco
- Investigators
- Sabine Mueller, MD, PhD, MAS, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03086616
- Sponsor's protocol ID
- 160816
- Other IDs
- NCI-2017-01829
- Status last verified
- Apr 2023
- First submitted
- 16 Mar 2017
- Last updated
- 6 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data after de-identification.
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I and Early Efficacy Study of Convection Enhanced Delivery of Irinotecan Liposome Injection Using Real Time Imaging With Gadolinium in Children With Diffuse Intrinsic Pontine Glioma
- ClinicalTrials.gov ID
- NCT03086616
- Acronym / sponsor ID
- 160816
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Keywords
- DIPG, CED, glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Sabine Mueller, MD, PhDUniversity, hospital or other
- Collaborators
- The V Foundation for Cancer Research, Pacific Pediatric Neuro-Oncology Consortium
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 4 Oct 2021 (actual)
- Study completion
- 4 Oct 2021 (actual)
- First posted
- 22 Mar 2017 (actual)
- 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.
This is a Phase I and Early Efficacy Study of Convection Enhanced Delivery (CED) of irinotecan liposome injection (nal-IRI) Using Real Time Imaging with Gadolinium in Children with Diffuse Intrinsic Pontine Glioma who have completed focal radiotherapy
Detailed description
This study will assess the safety and tolerability of repeated administration of nal-IRI co-infused with gadoteridol given by intratumoral CED in children with newly diagnosed DIPG.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Newly Diagnosed DIPG | Experimental | Drug: Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI): Nal-IRI given directly into the tumor using a method called CED to newly diagnosed DIPG subjects after completion of radiotherapy. CED will be performed every 4-8 weeks. Drug concentration will start at 20mg/ml and escalate up to 40 mg/ml concentration. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Patients with newly diagnosed DIPG by MRI; defined as patients with a pontine location and diffuse involvement of at least 2/3 of the pons are eligible without histologic diagnosis. For lesions with typical imaging features, biopsy is neither encouraged nor required for eligibility. Tumors that are biopsied will be eligible if proven to be supportive of the diagnosis of a DIPG. Consensus of diagnosis by the study team must be met.
- Treatment must begin at a minimum of 4 weeks after, but no later than 14 weeks after, the date of the completion of focal radiotherapy.
- Prior Chemotherapy: Patients should be at least 30 days from last chemotherapy dose prior to start of CED infusion, with exception of antibody half-lives. For antibody therapies, at least 3 half-lives of the antibody after last dose of monoclonal antibody should have passed prior to CED infusion. Patients less than 30 days from last chemotherapy dose should be discussed with the study chair(s).
- Prior Radiation: Patients must have completed prior treatment with standard focal radiotherapy as part of initial treatment for DIPG and had their last dose at least 4 weeks prior to and no later than 14 weeks from the first CED treatment. Patients beyond 14 weeks from radiation therapy but with stable disease should be discussed with the study chair.
- Age ≥ 2 years of age. Patients younger than 3 years of age may be enrolled on study at the discretion of the Study Chair(s) if supporting evidence that brainstem lesion represents a brainstem glioma.
Key exclusion criteria (11 listed)
- Patients who had clinical and/or radiographic (MRI) progression of tumor following external beam radiation therapy.
- Patients with metastatic disease, including leptomeningeal or subarachnoid disseminated disease.
- Patients with tumor morphology or other imaging findings that predict poor coverage of the majority of the tumor including significant tumor volume outside the pons or presence of large cysts within the tumor that would prevent adequate tumor coverage by CED. Patients with concern for adequate tumor coverage based on tumor morphology should be discussed with the study chairs.
- Patients who are receiving any other tumor-directed therapy
- Patients with MRI or clinical evidence of uncontrolled tumor mass effect are excluded; the patients should be discussed with the study chair(s) and study neurosurgeon prior to any planned CED treatment.
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 |
|---|---|---|
| Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)Also: Irinotecan Liposome InjectionNal-IRI will be given directly into the tumor using CED. | Drug | Newly Diagnosed DIPG |
Primary outcome
Number of Participants Experiencing Treatment-Related Adverse Events (AE)
Time frame: 12 months
Safety of repeated CED of nal-IRI following standard of care focal radiotherapy will be assessed by monitoring for adverse events, scheduled laboratory assessments, vital sign measurements, and physical examinations for subjects who receive the vaccination. The severity of toxicities will be graded according to the NCI CTCAE v4.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to study drug(s). Grade 1 and 2 adverse events will be summarized if related to study therapy. Descriptive statistics will be utilized to display the data on toxicity
1 secondary outcome
Overall Survival (OS) at 12 months (OS12)
Time frame: 12 months
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 6 Apr 2023.
- Individual participant dataSharing planned: Yes. Individual participant data after de-identification.
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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.
Sabine Mueller, MD, PhD, MAS study chair
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI) in people with Diffuse Intrinsic Pontine Glioma, run by Sabine Mueller, MD, PhD 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 19 inclusion and 11 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 6 Apr 2023. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Number of Participants Experiencing Treatment-Related Adverse Events (AE) (time frame: 12 months). 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 6 Apr 2023.