Study of Imatinib in Children With Neurofibromatosis and Airway Tumors

Phase 2 Study of Imatinib in Children With Neurofibromatosis and Airway Tumors

The purpose of this study is to look at a subset of plexiform neurofibromas and determine if the airway tumors are more sensitive to imatinib therapy. Funding Source - FDA OOPD

Study Overview

• Status: Withdrawn
• Conditions: Neurofibroma, Plexiform
• Intervention / Treatment: Drug: Imatinib Mesylate

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children - Indiana University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged: > 6 months and < 12 years of age.
2. Diagnosis of neurofibromatosis type 1 (NF1).
3. Presence of symptomatic airway plexiform neurofibromas ; defined by abnormal sleep study or pulmonary function testing.
4. Patients must have measurable (> 1.5 cm in two dimensions or able to assess a minimum of 3 slices) disease by magnetic resonance imaging (MRI).
5. Patients must have a Karnofsky of > 70% or Lansky of > 50% and a life expectancy of > 2 months.

6. Adequate end organ function, defined as the following:

   total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL, creatinine < 1.5 x ULN, ANC > 1.5 x 109/L, platelets > 100 x 109/L.

7. Patients must be able to swallow whole pills or crushed pills in a soft food such as pudding or apple sauce; or have other GI access such as a G-tube.
8. Written, voluntary informed consent/assent.

Exclusion Criteria:

1. Patient has received any other investigational agents within 14 days of first day of study drug dosing.
2. Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
3. Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
4. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
5. Patient has a known brain metastasis. Non-specific CNS changes on MRI/CT characteristic of NF1 are allowed, but not known CNS malignancies requiring therapeutic intervention.
6. Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
7. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
8. Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to study entry.
9. Patient previously received radiotherapy to > 25 % of the bone marrow
10. Patient had a major surgery within 2 weeks prior to study entry.
11. Patient/parent with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
12. Patients who have or anticipate receiving permanent (or semi-permanent) metallic structures attached to their body. (e.g., braces on teeth, body piercings), which their physicians believe will interfere with the MRI.
13. Patient has an unstable airway requiring more urgent intervention or deemed unable to travel due to unstable airway by referring MD.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Imatinib Mesylate Arm; Imatinib Mesylate, given daily orally, 55 mg PO BID, if tolerated for 2 weeks increase to 110 mg/m2 BID, and further increase to 165 and final dosage to 220 mg/m2 bid if tolerated. Can continue for 12 months.	Drug: Imatinib Mesylate; Imatinib given orally as dose escalation treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Functional Airway Response	Sleep study or pulmonary function test	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiologic response of tumor	Volumetric MRI measurements	12 months
Quality of Life Assessment	Quality of Life Questionnaire	12 months
Cytokine Biomarker	Immunoassay	12 months
Inflammatory Cell Biomarker	Flow cytometry	12 months

Collaborators and Investigators

• Sponsor: Indiana University

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2018
• Primary Completion (ACTUAL): September 1, 2020
• Study Completion (ANTICIPATED): September 1, 2021

Study Registration Dates

• First Submitted: September 11, 2018
• First Submitted That Met QC Criteria: September 26, 2018
• First Posted (ACTUAL): September 28, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibroma, Plexiform; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: 1505569560; 1R01FD004830-01A2 (FDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No