Diffuse Intrinsic Pontine GliomaPhase 1/2PNOC015NCT03566199
MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma
A Phase 1/2 study testing Panobinostat Nanoparticle Formulation MTX110 and Convection-Enhanced Delivery (CED) in people with Diffuse Intrinsic Pontine Glioma, run by Sabine Mueller, MD, PhD at 1 site in United States.
Trial summary
This phase I/II trial studies the side effects of panobinostat nanoparticle formulation MTX110 (MTX110) in treating participants with newly-diagnosed diffuse intrinsic pontine glioma. Panobinostat nanoparticle formulation MTX110 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Panobinostat Nanoparticle Formulation MTX110 and Convection-Enhanced Delivery (CED)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 22 May 2018to 31 Mar 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with newly diagnosed DIPG by magnetic resonance imaging (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.
- Patients who have completed focal radiotherapy within 14 weeks from time of enrollment are eligible.
- Treatment must begin at a minimum of 4 weeks after, but no later than 14 weeks after, the date of 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 received prior treatment with 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. Standard focal radiation therapy will include 54 to 60 Gy by external beam radiotherapy to the brainstem.
- Age ≥ 2 years of age to 21 years. 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.
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- Karnofsky Performance Score ≥ 50 for patients > 16 years of age and Lansky Performance Score ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are able to mobilize using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- 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.
- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm^3.
- Hemoglobin ≥ 8g/dl.
- Platelet count ≥ 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
- Normal coagulation defined as normal International Normalized Ratio (INR) or per institutional guidelines.
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 milliliters (mL)/minute (min)/1.73 m^2.
- A serum creatinine (mg/dL) based on age/gender as follows:
- Age: 2 to < 6 years; Male: 0.8; Female: 0.8
- Age: 6 to < 10 years; Male: 1; Female: 1
- Age: 10 to < 13 years; Male: 1.2; Female: 1.2
- Age: 13 to < 16 years; Male:1.5; Female: 1.4
- Age ≥ 16 years; Male: 1.7; Female: 1.4
- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age.
- Serum glutamate pyruvate transaminase (SGPT) [alanine aminotransferase (ALT)] ≤ 110 U/L.
- Serum albumin ≥ 2 g/dL.
- Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.
- The effects of MTX110 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 MTX110 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.
- Able to understand, and willing to sign, a written informed consent document.
- Patients who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
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 that predicts poor coverage of the majority of the tumor including bilateral thalamic involvement, or cysts that represent > 50% of cross-sectional areas of the pons. These subjects should be discussed with the study chairs.
- Patients who are receiving any other investigational agents or other tumor-directed therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to MTX110 or gadolinium.
- 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.
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- 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 with MRI or clinical evidence of uncontrolled tumor mass effect are excluded; the assessment of mass effect should be made by the study chairs and study neurosurgeons prior to any planned CED treatment.
- Untreated symptomatic hydrocephalus determined by treating physician.
- Patients with evidence of intra-tumoral hemorrhage > 5 mm maximal diameter. These subjects should be discussed with the study chair.
- Subjects with prolonged corrected QT (QTc) (> 450 msec) will be excluded from the study.
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: An Open Label Single Arm Phase I/II Study of MTX110 Delivered by Convection-enhanced Delivery (CED) in Patients With Diffuse Intrinsic Pontine Glioma (DIPG) Previously Treated With External Beam Radiation Therapy
This phase I/II trial studies the side effects of panobinostat nanoparticle formulation MTX110 (MTX110) in treating participants with newly-diagnosed diffuse intrinsic pontine glioma. Panobinostat nanoparticle formulation MTX110 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety and tolerability of repeated administration of MTX110 co-infused with gadoteridol given by intratumoral convection enhanced delivery in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
SECONDARY OBJECTIVES:
- To determine the clinical efficacy of repeated administration of MTX110 given by intratumoral convection-enhanced delivery (CED) in children with newly diagnosed DIPG in the confines of a phase I and early efficacy study.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Participants receive panobinostat nanoparticle formulation MTX110 intratumorally (IT) by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment participants are followed up at 30 days and then every 2 months.
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Being tested
- Panobinostat Nanoparticle Formulation MTX110, Convection-Enhanced Delivery (CED)
- 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.
Panobinostat Nanoparticle Formulation MTX110Drug
Also called MTX-110, MTX110 (CN)
Given IT
Convection-Enhanced Delivery (CED)Drug
Also called CED
Undergo CED
| Study group | Role | What they receive |
|---|---|---|
| Treatment (MTX110) | Experimental | Participants receive panobinostat nanoparticle formulation MTX110 IT by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Receives: Drug: Panobinostat Nanoparticle Formulation MTX110; Drug: Convection-Enhanced Delivery (CED) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants With Grade 3 or Higher, Treatment-related, Adverse Events
Adverse events and clinically significant laboratory abnormalities which meet Grade 3, 4, or 5 criteria according to Common Terminology Criteria for Adverse Events (CTCAE) classified by investigators and treating physicians as related to study treatment (probable, possible, and definite) will be summarized by maximum intensity/grade. Adverse events will be graded according to CTCAE version 4.0.
Measured: Up to 12 Months
Secondary outcomes (1)
Overall Survival Rate (OS) at 12 Months
Overall survival is defined as the percentage of participants alive from time of diagnosis up to 12 months.
Measured: Up to 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2018
- Study start22 May 2018
- Primary completion31 Mar 2021
- Study completion31 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sabine Mueller, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Midatech Pharma US Inc., Pacific Pediatric Neuro-Oncology Consortium
- Responsible party
- Sponsor-investigator, Sabine Mueller, MD, PhD, University of California, San Francisco
- Investigators
- Sabine Mueller, M.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03566199
- Sponsor's protocol ID
- 170817
- Other IDs
- NCI-2018-01085, PNOC015
- Acronym
- PNOC015
- Status last verified
- Feb 2022
- First submitted
- 12 Jun 2018
- Last updated
- 25 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Single Arm Phase I/II Study of MTX110 Delivered by Convection-enhanced Delivery (CED) in Patients With Diffuse Intrinsic Pontine Glioma (DIPG) Previously Treated With External Beam Radiation Therapy
- ClinicalTrials.gov ID
- NCT03566199
- Acronym / sponsor ID
- PNOC015 / 170817
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Sabine Mueller, MD, PhDUniversity, hospital or other
- Collaborators
- Midatech Pharma US Inc., Pacific Pediatric Neuro-Oncology Consortium
- Study start
- 22 May 2018 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 25 Jun 2018 (actual)
- Results
- Posted 25 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial studies the side effects of panobinostat nanoparticle formulation MTX110 (MTX110) in treating participants with newly-diagnosed diffuse intrinsic pontine glioma. Panobinostat nanoparticle formulation MTX110 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the safety and tolerability of repeated administration of MTX110 co-infused with gadoteridol given by intratumoral convection enhanced delivery in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
SECONDARY OBJECTIVES:
- To determine the clinical efficacy of repeated administration of MTX110 given by intratumoral convection-enhanced delivery (CED) in children with newly diagnosed DIPG in the confines of a phase I and early efficacy study.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Participants receive panobinostat nanoparticle formulation MTX110 intratumorally (IT) by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment participants are followed up at 30 days and then every 2 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (MTX110) | Experimental | Drug: Panobinostat Nanoparticle Formulation MTX110, Drug: Convection-Enhanced Delivery (CED)Participants receive panobinostat nanoparticle formulation MTX110 IT by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (27 listed)
- Patients with newly diagnosed DIPG by magnetic resonance imaging (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.
- Patients who have completed focal radiotherapy within 14 weeks from time of enrollment are eligible.
- Treatment must begin at a minimum of 4 weeks after, but no later than 14 weeks after, the date of 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 received prior treatment with 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. Standard focal radiation therapy will include 54 to 60 Gy by external beam radiotherapy to the brainstem.
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 that predicts poor coverage of the majority of the tumor including bilateral thalamic involvement, or cysts that represent > 50% of cross-sectional areas of the pons. These subjects should be discussed with the study chairs.
- Patients who are receiving any other investigational agents or other tumor-directed therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to MTX110 or gadolinium.
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 |
|---|---|---|
| Panobinostat Nanoparticle Formulation MTX110Also: MTX-110, MTX110 (CN)Given IT | Drug | Treatment (MTX110) |
| Convection-Enhanced Delivery (CED)Also: CEDUndergo CED | Drug | Treatment (MTX110) |
Primary outcome
Proportion of Participants With Grade 3 or Higher, Treatment-related, Adverse Events
Time frame: Up to 12 Months
Adverse events and clinically significant laboratory abnormalities which meet Grade 3, 4, or 5 criteria according to Common Terminology Criteria for Adverse Events (CTCAE) classified by investigators and treating physicians as related to study treatment (probable, possible, and definite) will be summarized by maximum intensity/grade. Adverse events will be graded according to CTCAE version 4.0.
1 secondary outcome
Overall Survival Rate (OS) at 12 Months
Time frame: Up to 12 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Sabine Mueller, M.D. principal investigator
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 1/2 study testing Panobinostat Nanoparticle Formulation MTX110 and Convection-Enhanced Delivery (CED) 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 27 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 25 Feb 2022. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Proportion of Participants With Grade 3 or Higher, Treatment-related, Adverse Events (time frame: Up to 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 25 Feb 2022.