MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma

NCT03566199 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 170817NCI-2018-01085PNOC015
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diffuse Intrinsic Pontine Glioma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 12 Months

Secondary Outcomes (1)

• Overall Survival Rate (OS) at 12 Months

  Up to 12 Months

Study Arms (1)

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.

Drug: Panobinostat Nanoparticle Formulation MTX110; Drug: Convection-Enhanced Delivery (CED)

Interventions

Panobinostat Nanoparticle Formulation MTX110 DRUG

Given IT

Also known as: MTX-110, MTX110 (CN)

Treatment (MTX110)

Convection-Enhanced Delivery (CED) DRUG

Undergo CED

Also known as: CED

Treatment (MTX110)

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sabine Mueller, MD, PhD: lead
• Midatech Pharma US Inc.: collaborator
• Pacific Pediatric Neuro-Oncology Consortium: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Phase 2 expansion cohort was not activated at behest of pharmaceutical supplier.

Results Point of Contact

• Title: Dr. Sabine Mueller, MD, PhD.
• Organization: University of California, San Francisco

Sabine.Mueller@ucsf.edu

(415) 502-7301

Study Officials

• Sabine Mueller, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Neurology

Study Record Dates

• First Submitted: June 12, 2018
• First Posted: June 25, 2018
• Study Start: May 22, 2018
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: February 25, 2022
• Results First Posted: February 25, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)