Study of Imatinib Mesylate in Neurofibromatosis Type I Patients Aged 2 to 21 With Plexiform Neurofibromas

NCT02177825 | Terminated Phase 2 DMC

• 1 other identifier: PLNEU SJ 01
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial will test the hypothesis that inhibition of c-kit signalling pathways in pediatric patients with Neurofibromatosis Type I(NF-1) and progressing plexiform neurofibroma will result in objective reduction and/or inhibition of plexiform neurofibromas progression. This will be a Phase II study of imatinib mesylate given orally. Patients with stable or responding disease may receive the drug for a period not exceeding one year.

Conditions

Plexiform Neurofibromas

Outcome Measures

Primary Outcomes (1)

• Demonstrate the clinical benefit of imatinib in a pediatric patient population with progressing and metabolically active plexiform NFs

  Time to tumor progression as assessed by volumetric MRI and FDG-PETScan analysis at baseline, after 3, 6, 9, and 12 months on therapy.

  12 months

Secondary Outcomes (1)

• Changes in NF1 biomarkers after treatment with imatinib

  12 months

Other Outcomes (1)

• Evaluate trough plasma levels of imatinib and its active metabolite (NDMIL N-desmethyl imatinib) achieved in this pediatric population

  12 months

Study Arms (1)

Imatinib Mesylate

EXPERIMENTAL

Imatinib Mesylate at 110 mg/m2 up to 440mg/m2 PO per day for twelve months taken in one morning dose (if dose is less than 200 mg/day) or two doses (morning and evening)

Drug: Imatinib Mesylate

Interventions

Imatinib Mesylate DRUG

oral administration

Also known as: Imatinib

Imatinib Mesylate

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age Greater than or equal to 2 years and up to 21 years of age at time of study enrolment
• Diagnosis Patients with NF1 and an inoperable plexiform NFs that has the potential to cause significant morbidity.
• Patients must have measurable disease by magnetic resonance imaging (MRI) and progressive plexiform neurofibroma(s) with or without clinical symptoms.
• Patients must have a recent FDG-PET scan imaging study done in the last 3 months before being offered participation to the study
• Surgery/Residual disease: Patients are only eligible if complete tumor resection is not feasible, or if a patient with a surgical option refuses surgery. Evidence of recurrent or progressive disease is NOT necessary. Patients must be at least 21 days from surgery, if performed, prior to receiving their first dose of study drug
• Performance level Patients must have a Karnofsky of \> 70% or Lansky of \>50% and a life expectancy of \> 6 months.
• Previous use of imatinib is permitted if there was no progressive disease during treatment.
• Prior therapy Patients must be at least 28 days without any treatment before enrolment in this study.
• Patient is free of another primary malignancy except if the other primary malignancy neither currently clinically significant nor requiring active intervention.
• Organ function requirement
• Creatinine \< 1.5 x upper limit of normal (ULN)
• Total bilirubin \< 1.5 x ULN and SGOT and SGPT \< 2.5 x ULN
• ANC \> 1.5 x 109/L and Platelets \> 100 x 109/L
• Reproductive potential Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.

You may not qualify if:

• Patient has received any other investigational agents within 28 days of first day of study drug dosing.
• Patient with rapidly progressing disease may be enrolled before the 28 days period. In these cases, only the study chair can take this decision.
• Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria.
• Female patients who are pregnant or breast-feeding.
• 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 central nervous system (CNS) changes on MRI/CT characteristic of NF1 are allowed, but not known CNS malignancies.
• 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 prior to study entry.
• Patient previously received radiotherapy to greater than or equal to 25% of the bone marrow within 24 months.
• Patient had a major surgery within 2 weeks prior to study entry.
• Patient with any significant history of non-compliance to medical regimens.
• 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.

Sponsors & Collaborators

• St. Justine's Hospital: lead

Study Sites (1)

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

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 Officials

• Sébastien Perreault, MD/FRCPC

  St. Justine's Hospital

  PRINCIPAL INVESTIGATOR

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: Neurologist

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: June 30, 2014
• Study Start: June 1, 2014
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: April 8, 2019

Record last verified: 2019-04

Locations

CA (1)