Infusion of Panobinostat (MTX110) Into the Fourth Ventricle in Children and Adults With Recurrent Medulloblastoma
Primary Purpose
Medulloblastoma
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Treatment with MTX110
Sponsored by
About this trial
This is an interventional treatment trial for Medulloblastoma focused on measuring medulloblastoma, Malignant Neoplasms, Brain, MTX110, panobinostat, Antineoplastic
Eligibility Criteria
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
Sites / Locations
- The University of Texas Health Science Center at HoustonRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment with MTX110
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Change in disease progression as measured by an MRI
Change in disease progression as measured by an MRI
Change in disease progression as measured by lumbar CSF cytology
Change in disease progression as measured by lumbar CSF cytology
Full Information
NCT ID
NCT04315064
First Posted
March 17, 2020
Last Updated
June 20, 2023
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Midatech Pharma plc
1. Study Identification
Unique Protocol Identification Number
NCT04315064
Brief Title
Infusion of Panobinostat (MTX110) Into the Fourth Ventricle in Children and Adults With Recurrent Medulloblastoma
Official Title
Infusion of Panobinostat (MTX110) Into the Fourth Ventricle or Tumor Resection Cavity in Children and Adults With Recurrent Medulloblastoma: A Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 21, 2020 (Actual)
Primary Completion Date
December 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Midatech Pharma plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medulloblastoma
Keywords
medulloblastoma, Malignant Neoplasms, Brain, MTX110, panobinostat, Antineoplastic
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment with MTX110
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Treatment with MTX110
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of participants with grade 3 through grade 5 new neurological adverse events that are related to study drug
Description
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
Time Frame
4 months post intervention
Secondary Outcome Measure Information:
Title
Change in disease progression as measured by an MRI
Description
Change in disease progression as measured by an MRI
Time Frame
prior to first infusion; after last infusion (last infusion is about 6 weeks after the first infusion)
Title
Change in disease progression as measured by lumbar CSF cytology
Description
Change in disease progression as measured by lumbar CSF cytology
Time Frame
prior to first infusion; after last infusion (last infusion is about 6 weeks after the first infusion)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David IIan Sandberg, MD
Phone
(713) 500-7370
Email
David.I.Sandberg@uth.tmc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Bangning Yu
Phone
(713) 500-7363
Email
Bangning.Yu@uth.tmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David IIan Sandberg, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Sandberg, MD
Phone
713-500-7370
Email
David.I.Sandberg@uth.tmc.edu
First Name & Middle Initial & Last Name & Degree
Bangning yu
Phone
(713) 500-7363
Email
Bangning.Yu@uth.tmc.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Infusion of Panobinostat (MTX110) Into the Fourth Ventricle in Children and Adults With Recurrent Medulloblastoma
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