Plexiform NeurofibromasPhase 2NCT02177825
Study of Imatinib Mesylate in Neurofibromatosis Type I Patients Aged 2 to 21 With Plexiform Neurofibromas
A Phase 2 study testing Imatinib Mesylate in people with Plexiform Neurofibromas, run by St. Justine's Hospital at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Plexiform Neurofibromas
- What is being tested?
- Imatinib Mesylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2014to 1 Mar 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of Imatinib Mesylate in Neurofibromatosis Type I Patients Aged 2 to 21 With Plexiform Neurofibromas
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.
Read the detailed description
Clinical objectives
- Demonstrate the clinical benefit of imatinib in a pediatric patient population with progressing and metabolically active plexiform neurofibromas (NF)
- Demonstrate the need or not to pursue treatment for more than a year in responders to imatinib
Biological studies objectives
- Identify biological markers of plexiform neurofibroma progression and response to treatment
- Identify biological markers of mast cell responses to imatinib, given that mast cells are required for tumorigenesis and are a target for imatinib
Imaging studies objectives
Using 18-Fluorodeoxyglucose-positron Emission Tomography (FDG PET/CT):
- Identify imaging characteristics of progressing plexiform neurofibromas
- Assess the role of F18-FDG PET/CT in comparison with CT/MRI to evaluate response to imatinib ¸
Pharmacological study
- Evaluate trough plasma levels of imatinib and its active metabolite (NDMIL N-desmethyl imatinib) achieved in this pediatric population
- Identify potential correlation between imatinib (and NDMI) trough levels achieved and clinical response
- Conditions
- Plexiform Neurofibromas
- Being tested
- Imatinib Mesylate
- Medical subject headings
- Neurofibroma, Plexiform
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib MesylateDrug
Also called Imatinib
oral administration
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Imatinib Mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (1)
Changes in NF1 biomarkers after treatment with imatinib
Patients on imatinib will have blood samples and urine taken at baseline and every 3 months until treatment completion or until disease progression. Mastocyte activation biomarkers will be monitored and evaluated as potential disease state indicators.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2014 (estimated)
- Study startJun 2014
- Primary completion1 Mar 2019
- Study completion1 Mar 2019
Why it stopped: Slow accrual 5 patients out of 25 expected. Primary objectives could not be met without recruiting more patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plexiform NeurofibromasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Justine's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Perreault, St. Justine's Hospital
- Investigators
- Sébastien Perreault, MD/FRCPC, Principal investigator, St. Justine's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02177825
- Sponsor's protocol ID
- PLNEU SJ 01
- Status last verified
- Apr 2019
- First submitted
- 25 Jun 2014
- Last updated
- 8 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Imatinib Mesylate in Neurofibromatosis Type I Patients Aged 2 to 21 With Plexiform Neurofibromas
- ClinicalTrials.gov ID
- NCT02177825
- Acronym / sponsor ID
- PLNEU SJ 01
- Conditions
- Plexiform Neurofibromas
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual 5 patients out of 25 expected. Primary objectives could not be met without recruiting more patients.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- St. Justine's HospitalUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- 1 Mar 2019 (actual)
- Study completion
- 1 Mar 2019 (actual)
- First posted
- 30 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Clinical objectives
- Demonstrate the clinical benefit of imatinib in a pediatric patient population with progressing and metabolically active plexiform neurofibromas (NF)
- Demonstrate the need or not to pursue treatment for more than a year in responders to imatinib
Biological studies objectives
- Identify biological markers of plexiform neurofibroma progression and response to treatment
- Identify biological markers of mast cell responses to imatinib, given that mast cells are required for tumorigenesis and are a target for imatinib
Imaging studies objectives
Using 18-Fluorodeoxyglucose-positron Emission Tomography (FDG PET/CT):
- Identify imaging characteristics of progressing plexiform neurofibromas
- Assess the role of F18-FDG PET/CT in comparison with CT/MRI to evaluate response to imatinib ¸
Pharmacological study
- Evaluate trough plasma levels of imatinib and its active metabolite (NDMIL N-desmethyl imatinib) achieved in this pediatric population
- Identify potential correlation between imatinib (and NDMI) trough levels achieved and clinical response
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib Mesylate | Experimental | Drug: Imatinib MesylateImatinib 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) |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- 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.
- 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.
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imatinib MesylateAlso: Imatiniboral administration | Drug | Imatinib Mesylate |
Primary outcome
Demonstrate the clinical benefit of imatinib in a pediatric patient population with progressing and metabolically active plexiform NFs
Time frame: 12 months
Time to tumor progression as assessed by volumetric MRI and FDG-PETScan analysis at baseline, after 3, 6, 9, and 12 months on therapy.
1 secondary outcome
Changes in NF1 biomarkers after treatment with imatinib
Time frame: 12 months
Results and safety
The study was stopped early (reason given: Slow accrual 5 patients out of 25 expected. Primary objectives could not be met without recruiting more patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sébastien Perreault, MD/FRCPC principal investigator
St. Justine's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib Mesylate in people with Plexiform Neurofibromas, run by St. Justine's Hospital at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow accrual 5 patients out of 25 expected. Primary objectives could not be met without recruiting more patients.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Demonstrate the clinical benefit of imatinib in a pediatric patient population with progressing and metabolically active plexiform NFs (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2019.