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

Medulloblastoma Clinical Trial

Official title:

Infusion of Panobinostat (MTX110) Into the Fourth Ventricle or Tumor Resection Cavity in Children and Adults With Recurrent Medulloblastoma: A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04315064
• Other study ID #: HSC-MS-19-0939
• Status: Recruiting
• Phase: Early Phase 1
• Start date: April 21, 2020
• Est. completion date: December 30, 2025

Study information

• Verified date: May 2024
• Source: The University of Texas Health Science Center, Houston
• Contact: David IIan Sandberg, MD
• Phone: (713) 500-7370
• Email: David.I.Sandberg[@]uth.tmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Medulloblastoma

Intervention

Drug:
• Treatment with MTX110
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.

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at Houston	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	Midatech Pharma plc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in disease progression as measured by an MRI	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)
Secondary	Change in disease progression as measured by lumbar CSF cytology	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)