Infusion of Panobinostat (MTX110) Into the Fourth Ventricle in Children and Adults with Recurrent Medulloblastoma

NCT04315064 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: HSC-MS-19-0939
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to establish the safety of infusions of panobinostat (MTX110) into the fourth ventricle of the brain or tumor resection cavity in patients with recurrent medulloblastoma and to assess the antitumor activity of simultaneous infusions of panobinostat (MTX110) into the fourth ventricle of the brain or resection cavity in patients with recurrent medulloblastoma based upon MRI scans and lumbar cerebrospinal fluid (CSF) cytology.

Conditions

Medulloblastoma

Keywords

medulloblastoma; Malignant Neoplasms, Brain; MTX110; panobinostat; Antineoplastic

Outcome Measures

Primary Outcomes (1)

• Number of participants with grade 3 through grade 5 new neurological adverse events that are related to study drug

  Anew neurological deficit will be defined as new cranial neuropathy, change in level of consciousness, motor weakness, gait change or cerebellar finding (ataxia, dysmetria, dysdiadochokinesis) and will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0

  4 months post intervention

Secondary Outcomes (2)

• Change in disease progression as measured by an MRI

  prior to first infusion; after last infusion (last infusion is about 6 weeks after the first infusion)

• Change in disease progression as measured by lumbar CSF cytology

  prior to first infusion; after last infusion (last infusion is about 6 weeks after the first infusion)

Study Arms (1)

Treatment with MTX110

EXPERIMENTAL

Drug: Treatment with MTX110

Interventions

Treatment with MTX110 DRUG

Patients will undergo surgery for maximum safe tumor resection with simultaneous placement of a ventricular access device (VAD) into the fourth ventricle or posterior fossa tumor resection cavity.The specific ventricular access device that will be placed is Medtronic Reference number 44102, "Medtronic CSF-Ventricular Reservoir Side Inlet, 18 mm.If a patient already has a ventricular access device in place and additional tumor resection is not required, then that patient can proceed with intraventricular chemotherapy infusions after study enrollment. If the patient has metastatic disease in the brain and/or spine without resectable tumor in the posterior fossa, then only catheter and ventricular access device placement will be performed.Enrolled patients will receive 4 infusions per week of panobinostat (MTX110; 0.25 ml of 300 μM = 26.2 μg), per infusion into the ventricular access device for 6 consecutive weeks for a total of 24 infusions.

Treatment with MTX110

Eligibility Criteria

• Age: 1 Year - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis: Patients with histologically verified medulloblastoma with recurrence or progression involving anywhere in the brain and/or spine.
• Patient must have either measurable or evaluable tumor as assessed by MRI of the brain and total spine
• An implanted catheter in the fourth ventricle or posterior fossa tumor cavity attached to a ventricular access device or agreement to have one placed.
• A minimum of 7 days between last dose of systemic chemotherapy and/or radiation therapy and first infusion of chemotherapy into fourth ventricle
• Life expectancy of at least 12 weeks in the opinion of the principal investigator
• Lansky score of 50 or greater if ≤16 years of age or Karnofsky score of 50 or greater if \> 16 years of age
• Existing neurological deficits must have been stable for a minimum of 1 week prior to study enrollment
• Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy
• Adequate bone marrow function defined by peripheral absolute neutrophil count (ANC) ≥ 500/µL, platelet count ≥ 50,000/µL (transfusion independent), and hemoglobin ≥ 9.0 gm/dL (may receive red blood cells(RBC) transfusions)
• Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.
• Patient with prolonged QT interval on screening EKG will need cardiology consultation prior to enrollment
• Patients with abnormal liver function tests (ALT, Aspartate Aminotransferase(AST),or total bilirubin) will need gastroenterology consultation prior to enrollment

You may not qualify if:

• Enrolled in another treatment protocol
• Has received another investigational or chemotherapy agent or radiation therapy within 7 days prior to intraventricular chemotherapy infusions
• Evidence of untreated infection
• Pregnant or lactating women

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• Midatech Pharma plc: collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Medulloblastoma; Brain Neoplasms

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

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

Study Officials

• David IIan Sandberg, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 19, 2020
• Study Start: April 21, 2020
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)