Plexiform Neurofibroma Associated With Neurofibromatosis Type 1Phase 2NCT01365468
Efficacy and Safety of RAD001 in Treating Plexiform Neurofibromas (PN) Associated With Neurofibromatosis (NF1)
A Phase 2 study testing Everolimus (RAD001) in people with Plexiform Neurofibroma Associated With Neurofibromatosis Type 1, run by Novartis Pharmaceuticals at 2 sites in Israel.
Trial summary
This study was to evaluate the antitumor activity and safety of RAD001 in patients with Plexiform neurofibromas (PN) associated with Neurofibromatosis Type 1 (NF1). The aim of the study was to : 1. determine whether RAD001, administrated orally daily on a continuous dosing schedule might: 1. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Plexiform Neurofibroma Associated With Neurofibromatosis Type 1
- What is being tested?
- Everolimus (RAD001)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesIsrael
- Study dates
- Apr 2012to Apr 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinically definite diagnosis of NF1 according to the NIH consensus conference criteria.
- Patients must have PN that have the potential to cause significant morbidity, such as lesions that could compromise the airway or the great vessels, lesions that could cause nerve compression, lesions that could result in major deformity or significant cosmetic problems
- Measurable disease: patient must have at least one measurable PN amenable to volumetric MRI analysis.
Who cannot join
- Chronic treatment with systemic steroids or another immunosuppressive agent.
- Evidence of an active optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiation therapy.
- Clinical evidence of significantly impaired lung function
- Pregnancy or breast feeding.
- Prior therapy with mTOR inhibitors (e.g.sirolimus, temsirolimus, everolimus).
- No contraindications for MRI assessments
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
Novartis Investigative Site
Tel Aviv, 6423906
Novartis Investigative Site
Tel HaShomer, 52621
About this study
Official title: A Phase II Study of RAD001 in the Treatment of Patients With Plexiform Neurofibromas (PN) Associated With Neurofibromatosis Type 1 (NF1)
This study was to evaluate the antitumor activity and safety of RAD001 in patients with Plexiform neurofibromas (PN) associated with Neurofibromatosis Type 1 (NF1).
The aim of the study was to :
- determine whether RAD001, administrated orally daily on a continuous dosing schedule might:
- Increases time to disease progression (TTP) based on volumetric MRI measurements in children and adults with NF1 in inoperable documented progressive PN (stratum 1).
- Results in objective radiographic responses based on volumetric MRI measurements in children and adults with NF1 and inoperable PN in the absence of documented radiographic progression at the trail entry (stratum
- To evaluate the tolerability and toxicity of chronic RAD001 administration in this patient population as assessed by the NCI Common Toxicity Criteria, version 4.0.
Read the detailed description
Approximately 20 patients were to be enrolled to receive everolimus in an open label manner. A total of 9 patients were enrolled to either Stratum 1 or Stratum 2.
The study was open for enrollment up to 2 years. Because the target enrollment was not achieved in this period, study was terminated with less patient than planned.
- Being tested
- Everolimus (RAD001)
- Keywords
- RAD001,, Everolimus,, Plexiform Neurofibroma,, Neurofibromatosis Type 1
- Medical subject headings
- Neurofibroma, Plexiform, Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus (RAD001)Drug
oral daily dosing of tablet starting with 2.5 mg
| Study group | Role | What they receive |
|---|---|---|
| Everolimus (RAD001) | Experimental | enrolled patients received everolimus (RAD001) in an open label manner. Recommended starting dose of everolimus depend on body surface area, starting from 2.5 mg once daily to 7.5 mg once daily. Receives: Drug: Everolimus (RAD001) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only)
This endpoint was planned to be analyzed for only Stratum 1 patients. Progression of disease defined as a ≥ 20% increase in the volume (by volumetric MRI) of at least one of the index plexiform neurofibromas (PN) compared to the pretreatment volume measured prior to the start of the current treatment phase.
Measured: Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days)
Number of Patients With Objective Radiographic Responses Based on Volumetric MRI Measurements (In Stratum 2 Only)
Response was assessed at the time that a follow up volumetric MRI scan is performed (after course 6 and then every 6 months and at the end of treatment).
- Complete response (CR): complete resolution of all measurable or palpable PN for ≥ 28days and no appearance of new lesions.
- Partial response (PR): A ≥ 20% reduction in the sum of the volume of all index PN lesions for ≥ 28days.
- Stable disease (SD): A < 20% increase and < 20% decrease in the sum of the volume of all index PN lesions for ≥ 28days.
Measured: Screening, after course #6, then every 6 months and end of treatment(1 course=28days)
Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04
Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0. If CTCAE grading does not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to grades 1 - 4 respectively, were used. CTCAE grade 5 (death) was not used in this study.
Measured: From the time ICF was signed until 28 days after End of Treatment (up to a maximum of 25 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2011 (estimated)
- Study startApr 2012
- Primary completionApr 2015
- Study completionApr 2015
Why it stopped: Poor patients' accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Plexiform Neurofibroma Associated With Neurofibromatosis Type 1Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01365468
- Sponsor's protocol ID
- CRAD001MIL04T
- Status last verified
- May 2016
- First submitted
- 27 May 2011
- Last updated
- 12 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of RAD001 in the Treatment of Patients With Plexiform Neurofibromas (PN) Associated With Neurofibromatosis Type 1 (NF1)
- ClinicalTrials.gov ID
- NCT01365468
- Acronym / sponsor ID
- CRAD001MIL04T
- Keywords
- RAD001,, Everolimus,, Plexiform Neurofibroma,, Neurofibromatosis Type 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor patients' accrual
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2012
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 3 Jun 2011 (estimated)
- Results
- Posted 12 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was to evaluate the antitumor activity and safety of RAD001 in patients with Plexiform neurofibromas (PN) associated with Neurofibromatosis Type 1 (NF1).
The aim of the study was to :
- determine whether RAD001, administrated orally daily on a continuous dosing schedule might:
- Increases time to disease progression (TTP) based on volumetric MRI measurements in children and adults with NF1 in inoperable documented progressive PN (stratum 1).
- Results in objective radiographic responses based on volumetric MRI measurements in children and adults with NF1 and inoperable PN in the absence of documented radiographic progression at the trail entry (stratum
- To evaluate the tolerability and toxicity of chronic RAD001 administration in this patient population as assessed by the NCI Common Toxicity Criteria, version 4.0.
Detailed description
Approximately 20 patients were to be enrolled to receive everolimus in an open label manner. A total of 9 patients were enrolled to either Stratum 1 or Stratum 2.
The study was open for enrollment up to 2 years. Because the target enrollment was not achieved in this period, study was terminated with less patient than planned.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus (RAD001) | Experimental | Drug: Everolimus (RAD001)enrolled patients received everolimus (RAD001) in an open label manner. Recommended starting dose of everolimus depend on body surface area, starting from 2.5 mg once daily to 7.5 mg once daily. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Clinically definite diagnosis of NF1 according to the NIH consensus conference criteria.
- Patients must have PN that have the potential to cause significant morbidity, such as lesions that could compromise the airway or the great vessels, lesions that could cause nerve compression, lesions that could result in major deformity or significant cosmetic problems
- Measurable disease: patient must have at least one measurable PN amenable to volumetric MRI analysis.
Key exclusion criteria (7 listed)
- Chronic treatment with systemic steroids or another immunosuppressive agent.
- Evidence of an active optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiation therapy.
- Clinical evidence of significantly impaired lung function
- Pregnancy or breast feeding.
- Prior therapy with mTOR inhibitors (e.g.sirolimus, temsirolimus, everolimus).
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 |
|---|---|---|
| Everolimus (RAD001)oral daily dosing of tablet starting with 2.5 mg | Drug | Everolimus (RAD001) |
Primary outcome
Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only)
Time frame: Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days)
This endpoint was planned to be analyzed for only Stratum 1 patients. Progression of disease defined as a ≥ 20% increase in the volume (by volumetric MRI) of at least one of the index plexiform neurofibromas (PN) compared to the pretreatment volume measured prior to the start of the current treatment phase.
Number of Patients With Objective Radiographic Responses Based on Volumetric MRI Measurements (In Stratum 2 Only)
Time frame: Screening, after course #6, then every 6 months and end of treatment(1 course=28days)
Response was assessed at the time that a follow up volumetric MRI scan is performed (after course 6 and then every 6 months and at the end of treatment). * Complete response (CR): complete resolution of all measurable or palpable PN for ≥ 28days and no appearance of new lesions. * Partial response (PR): A ≥ 20% reduction in the sum of the volume of all index PN lesions for ≥ 28days. * Stable disease (SD): A < 20% increase and < 20% decrease in the sum of the volume of all index PN lesions for ≥ 28days.
Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04
Time frame: From the time ICF was signed until 28 days after End of Treatment (up to a maximum of 25 months)
Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0. If CTCAE grading does not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to grades 1 - 4 respectively, were used. CTCAE grade 5 (death) was not used in this study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus (RAD001) in people with Plexiform Neurofibroma Associated With Neurofibromatosis Type 1, run by Novartis Pharmaceuticals at 2 sites in Israel.
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 3 inclusion and 7 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 12 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. 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?
Yes. Results are posted in the registry (first posted 12 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only) (time frame: Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days)). The study lists 3 primary outcomes in all. 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 12 May 2016.