Study of Imatinib in Children With Neurofibromatosis and Airway Tumors

NCT03688568 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 15055695601R01FD004830-01A2
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Neurofibroma, Plexiform

Outcome Measures

Primary Outcomes (1)

• Quantitative Functional Airway Response

  Sleep study or pulmonary function test

  12 months

Secondary Outcomes (4)

• Radiologic response of tumor

  12 months

• Quality of Life Assessment

  12 months

• Cytokine Biomarker

  12 months

• Inflammatory Cell Biomarker

  12 months

Study Arms (1)

Imatinib Mesylate Arm

EXPERIMENTAL

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

Interventions

Imatinib Mesylate DRUG

Imatinib given orally as dose escalation treatment.

Imatinib Mesylate Arm

Eligibility Criteria

• Age: 6 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients aged: \> 6 months and \< 12 years of age.
• Diagnosis of neurofibromatosis type 1 (NF1).
• Presence of symptomatic airway plexiform neurofibromas ; defined by abnormal sleep study or pulmonary function testing.
• 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).
• Patients must have a Karnofsky of \> 70% or Lansky of \> 50% and a life expectancy of \> 2 months.
• 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.
• 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.
• Written, voluntary informed consent/assent.

You may not qualify if:

• Patient has received any other investigational agents within 14 days of first day of study drug dosing.
• 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.
• 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)
• Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
• 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.
• Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to study entry.
• Patient previously received radiotherapy to \> 25 % of the bone marrow
• Patient had a major surgery within 2 weeks prior to study entry.
• Patient/parent with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
• 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.
• Patient has an unstable airway requiring more urgent intervention or deemed unable to travel due to unstable airway by referring MD.

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Riley Hospital for Children - Indiana University

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Neurofibroma, Plexiform

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 28, 2018
• Study Start: September 1, 2018
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2021
• Last Updated: February 12, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)