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Trial record 64 of 161 for:    Genetic | "neurofibromatosis type 2" OR "neurofibromatosis"

A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis Type 1 Related Plexiform Neurofibromas (Protocol 102)

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ClinicalTrials.gov Identifier: NCT00634270
Recruitment Status : Completed
First Posted : March 13, 2008
Results First Posted : February 14, 2017
Last Update Posted : November 17, 2017
Sponsor:
Collaborators:
Boston Children’s Hospital
Children's Hospital of Philadelphia
Children's Research Institute
Children's Hospital Medical Center, Cincinnati
National Cancer Institute (NCI)
University of Chicago
University of Utah
Washington University School of Medicine
Information provided by (Responsible Party):
Bruce Korf, MD, University of Alabama at Birmingham

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neurofibromatosis Type 1
Intervention Drug: Sirolimus
Enrollment 58

Recruitment Details Existing and NF1 new patients at Consortium sites and partnering with the Children's Tumor Foundation.
Pre-assignment Details Eligibility for Stratum 1 if evidence of progression and Stratum 2 if not evidence of progression.
Arm/Group Title Stratum 1 Stratum 2
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Design

  • Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.
  • Disease status will be evaluated using volumetric MRI analysis at regular intervals.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
Period Title: Overall Study
Started 49 [1] 13
Completed 46 12
Not Completed 3 1
[1]
February 12, 2008
Arm/Group Title Stratum 1 Stratum 2 Total
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Design

  • Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.
  • Disease status will be evaluated using volumetric MRI analysis at regular intervals.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression Total of all reporting groups
Overall Number of Baseline Participants 49 13 62
Hide Baseline Analysis Population Description
Of the 49 patients enrolled in Stratum 1; 46 were evaluable. Of the 13 enrolled in Stratum 2; 12 were evaluable. This information is also listed in the Analysis Population Descriptions and Additional Description.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 49 participants 13 participants 62 participants
9
(3 to 45)
16
(3 to 35)
10.46
(3 to 45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 13 participants 62 participants
Female
24
  49.0%
8
  61.5%
32
  51.6%
Male
25
  51.0%
5
  38.5%
30
  48.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 49 participants 13 participants 62 participants
American Indian or Alaskan Native 0 0 0
Asian 3 1 4
Native Hawaiian or Pacific Islander 0 0 0
Black or African American 6 2 8
White 35 10 45
Unknown or Not Reports 5 0 5
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 49 participants 13 participants 62 participants
49 13 62
1.Primary Outcome
Title Time to Disease Progression Based on Volumetric MRI
Hide Description Median time to progression in Stratum 1 as defined as an increase of at least 20% of the volume of the primary lesion. Note: Since Stratum 2 looked at response rate only, median time to progression was not reviewed for this outcome.
Time Frame 24 Months Stratum 1
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Hide Analysis Population Description
All evaluable participants. Note: In Stratum 2 the value was not assessed as "time to progression" therefore the appropriate response would be N/A. Stratum 2 was reported as response rate only.
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description:

Design

  • Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.
  • Disease status will be evaluated using volumetric MRI analysis at regular intervals.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
Overall Number of Participants Analyzed 46 0
Median (95% Confidence Interval)
Unit of Measure: Months
15.4
(14.3 to 23.7)
2.Primary Outcome
Title 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 Trial Entry
Hide Description Stratum 2 outcome - Response
Time Frame 48 weeks Stratum 2
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Hide Analysis Population Description
Identify the index plexiform neurofibroma(s) for 3-D MRI evaluation based on prior imaging studies. The criteria for response was <20% increase in volume using RECIST v1.0. Response for 48 weeks was only assessed for Stratum 2.
Arm/Group Title Stratum 2
Hide Arm/Group Description:
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: participants
12
3.Primary Outcome
Title Toxicity
Hide Description Number of participants experiencing adverse events
Time Frame 24 weeks Stratum 1 / 48 weeks Stratum 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable participants for Stratum 1 and 2 combined.
Arm/Group Title Stratum 1 Stratum 2
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Patients ≥ 3 years old with progressive plexiform neurofibroma(s) with the potential to cause significant morbidity.
Patients ≥ 3 years old and plexiform neurofibroma(s) without documented radiographic progression at trial entry. The endpoint will be radiographic response.
Overall Number of Participants Analyzed 49 13
Measure Type: Number
Unit of Measure: Participants
49 13
4.Primary Outcome
Title To Characterize the Pharmacokinetic Profile of Sirolimus Administered to This Patient Population (Clearance Liters/Hour (L/h))
Hide Description An iterative 2-stage Bayesian method was used for the PK parameter analyses
Time Frame Pre-dose; Day 1 at 0.5 hours, 1.0 hours, 2.0 hours, 3.0 hours, 4.0 hours, 6.0 hours, 8.0 hours, and 10.0 to 12.0 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pediatric Patients (3 through 18) with Neurofibromatosis Type 1 - Clearance liters/hour (L/h). Stratum 2 did not meet the 6 month response criteria; therefore, was not analyzed for pharmacokinetic profiles.
Arm/Group Title Stratum 1
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Design

• Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: Clearance liters/hour (L/h)
11.8  (4.6)
5.Primary Outcome
Title To Characterize the Pharmacokinetic Profile of Sirolimus When Administered to This Patient Population Using Liters/Hour Per Population Median Weight of 70kg (L/h70kg)
Hide Description An iterative 2-stage Bayesian method was used for the PK parameter analyses
Time Frame Pre-dose; Day 1 at 0.5 hours, 1.0 hours, 2.0 hours, 3.0 hours, 4.0 hours, 6.0 hours, 8.0 hours, and 10.0 to 12.0 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Stratum 1 used allometrically scaled clearance (clearance scaled to a 70kg individual). Stratum 2 did not meet the 6 month response criteria; therefore, was not analyzed for pharmacokinetic profiles.
Arm/Group Title Stratum 1
Hide Arm/Group Description:

Design

• Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing. Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: L/h/70kg
23.7  (6.7)
6.Primary Outcome
Title To Characterize the Pharmacokinetic Profile of Sirolimus When Administered to This Patient Population - (Clearance (L/h Per 1.85 m^2)
Hide Description An iterative 2-stage Bayesian Method was used for the PK parameter analyses
Time Frame Pre-dose; Day 1 at 0.5 hours, 1.0 hours, 2.0 hours, 3.0 hours, 4.0 hours, 6.0 hours, 8.0 hours, and 10.0 to 12.0 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Stratum 1, Neurofibromatosis Type 1 Patients Clearance (L/h per 1.85 m^2). Stratum 2 did not meet the 6 month response criteria; therefore, was not analyzed for pharmacokinetic profiles.
Arm/Group Title Stratum 1
Hide Arm/Group Description:

Design

• Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause significant morbidity treated with sirolimus. The second stratum will evaluate objective radiographic response to sirolimus in children and adults with NF1 and inoperable plexiform neurofibromas with the potential to cause significant morbidity that do not have documented progression of the PN at time of trial entry.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: L/h per 1.85 m^2
6.4  (2.5)
7.Primary Outcome
Title To Characterize the Pharmacokinetic Profile of Sirolimus When Administered to This Patient Population- Therapeutic Dose (mg/m^2 Per Dose)
Hide Description An iterative 2-stage Bayesian Method was used for the PK parameter analyses
Time Frame Pre-dose; Day 1 at 0.5 hours, 1.0 hours, 2.0 hours, 3.0 hours, 4.0 hours, 6.0 hours, 8.0 hours, and 10.0 to 12.0 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Stratum 1, Neurofibromatosis Type 1 patients - Therapeutic Dose (mg/m^2 per dose). Stratum 2 did not meet the 6 month response criteria; therefore, was not analyzed for pharmacokinetic profiles.
Arm/Group Title Stratum 1
Hide Arm/Group Description:

Design

• Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause significant morbidity treated with sirolimus. The second stratum will evaluate objective radiographic response to sirolimus in children and adults with NF1 and inoperable plexiform neurofibromas with the potential to cause significant morbidity that do not have documented progression of the PN at time of trial entry.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: Therapeutic Dose mg/m^2 per dose
2.0  (0.7)
8.Primary Outcome
Title To Characterize the Pharmacokinetic Profile of Sirolimus in When Administered to This Patient Population - Therapeutic Dose (mg/kg Per Dose)
Hide Description An iterative 2-stage Bayesian Method was used for the PK parameter analyses
Time Frame Pre-dose; Day 1 at 0.5 hours, 1.0 hours, 2.0 hours, 3.0 hours, 4.0 hours, 6.0 hours, 8.0 hours, and 10.0 to 12.0 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Stratum 1, Neurofibromatosis Type 1 patients (Ages 3 to 18) Therapeutic Dose (mg/kg per dose). Stratum 2 did not meet the 6 month response criteria; therefore, was not analyzed for pharmacokinetic profiles.
Arm/Group Title Stratum 1
Hide Arm/Group Description:

Design

• Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause significant morbidity treated with sirolimus. The second stratum will evaluate objective radiographic response to sirolimus in children and adults with NF1 and inoperable plexiform neurofibromas with the potential to cause significant morbidity that do not have documented progression of the PN at time of trial entry.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: Therapeutic Dose (mg/kg per dose)
0.08  (0.04)
9.Primary Outcome
Title To Characterize the Pharmacokinetic Profile of Sirolimus When Administered to This Patient Population - Therapeutic Dose (mg/kg)^0.75
Hide Description An iterative 2-stage Bayesian method was used for the PK parameter analyses
Time Frame Pre-dose; Day 1 at 0.5 hours, 1.0 hours, 2.0 hours, 3.0 hours, 4.0 hours, 6.0 hours, 8.0 hours, and 10.0 to 12.0 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Stratum 1, Neurofibromatosis Type 1 patients (ages 3 to 18) - Therapeutic Dose (mg/kg)^0.75. Stratum 2 did not meet the 6 month response criteria; therefore, was not analyzed for pharmacokinetic profiles.
Arm/Group Title Stratum 1
Hide Arm/Group Description:

Design

• Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause significant morbidity treated with sirolimus. The second stratum will evaluate objective radiographic response to sirolimus in children and adults with NF1 and inoperable plexiform neurofibromas with the potential to cause significant morbidity that do not have documented progression of the PN at time of trial entry.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: Therapeutic Dose (mg/kg)^0.75
0.14  (0.05)
10.Secondary Outcome
Title To Evaluate the Quality of Life During Treatment With Sirolimus by Assessing Preliminary Correlations of Response With Quality-of-life Outcomes
Hide Description Self-reported, age-appropriate PedsQL Scale. Assessments included: Inventory for physical function, emotional function, social function and school function - number system 0-4 was used with 4 being the worse maximum threshold); inventory for chronic illness used a 5-point likert scale - 5 being the worst maximum threshold; Skindex-Teen used a scale of 0 to 100 - the higher the number the more frequent the experience; Pain intensity was measured using a line with a happy and sad face - marks toward the sad face indicated more intense pain; and, the McGill Pain Questionnaire - higher values indicating worse pain of a scale from 0-3. All assessments were combined for an overall PedsQL score by rating each item 0-4, then reverse transforming each to a 0 - 100 scale. The total scores were calculated by averaging the item scores, with higher scores being better.
Time Frame 24 weeks Stratum 1 / 48 weeks Stratum 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Stratum 1 patients with Neurofibromatosis Type 1; all ages - Change from Baseline to Course 3. Stratum 2 did not meet the requirements for response at the 6 month time point. Therefore, Stratum 2 was not analyzed for this aim.
Arm/Group Title Stratum 1
Hide Arm/Group Description:

Design

• Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing. Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: Units on a scale
2.8  (9.59)
11.Secondary Outcome
Title To Assess the Value of Three-dimensional MRI (3-D MRI) in the Evaluation of Plexiform Neurofibromas and Paraspinal Neurofibromas, and to Compare 3-D MRI to Conventional Two-dimensional MRI (2-D MRI) and One Dimensional MRI (1-D MRI) Data Analysis
Hide Description The study provided central review of all MRIs using a three-dimensional volumetric protocol. As the STOPN protocol began, research had already demonstrated the superiority of this approach to 1-D or 2-D analyses, so these were not used in the STOPN study.
Time Frame 24 weeks Stratum 1 / 48 weeks Stratum 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The data for this outcome wasn't collected because prior to the study, it was determined that MRI (3-D MRI) was already superior, so the MRI was not performed on any of the participants
Arm/Group Title Stratum 1 Stratum 2
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Patients ≥ 3 years old with progressive plexiform neurofibroma(s) with the potential to cause significant morbidity.
Patients ≥ 3 years old and plexiform neurofibroma(s) without documented radiographic progression at trial entry. The endpoint will be radiographic response.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title To Asses Preliminary Correlations of Radiographic Response With Changes in Pharmacodynamics Parameters Including p70s6 Kinase Activity in Peripheral Blood Mononuclear Cells.
Hide Description Response by Volumetric MRI.
Time Frame 24 weeks Stratum 1 / 48 weeks Stratum 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Samples were inadequate in quantity to allow for this analysis.
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description:

Design

  • Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.
  • Disease status will be evaluated using volumetric MRI analysis at regular intervals.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title To Evaluate the Effect of Sirolimus on Clinical Response by Reduction in Pain, or Improvement in Function or Performance Scale.
Hide Description There were no data collected for this outcome measure.
Time Frame 24 weeks Stratum 1 / 48 weeks Stratum 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description:

Design

  • Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.
  • Disease status will be evaluated using volumetric MRI analysis at regular intervals.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title To Evaluate Pharmacogenetic Polymorphisms of Cytochrome P450 3A4 & 3A5 Alleles and P-glycoprotein/MDR for Their Influence on the Metabolism of Sirolimus in This Patient Population.
Hide Description Trough concentration of sirolimus is reported in nanograms per mL.
Time Frame 24 weeks Stratum 1 Only
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects in Stratum 1.
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description:

Design

  • Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.
  • Disease status will be evaluated using volumetric MRI analysis at regular intervals.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
Overall Number of Participants Analyzed 37 0
Mean (Standard Deviation)
Unit of Measure: ng/mL
9.37  (2.48)
15.Secondary Outcome
Title To Evaluate the Role of Apolipoprotein E Genotypes as Predictors for Development of Hyperlipidemia During Therapy With Sirolimus.
Hide Description Number of patients who experienced hyperlipidemia is being reported.
Time Frame 24 weeks Stratum 1 / 48 weeks Stratum 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description:

Design

  • Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing.
  • Disease status will be evaluated using volumetric MRI analysis at regular intervals.

Sirolimus, Rapamycin: This phase II study will evaluate children and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with sirolimus. It is divided in two strata. The first stratum will evaluate time to progression (TTP) in children and adults with NF1 and progressive plexiform neurofibromas with the potential to cause sign

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
Overall Number of Participants Analyzed 46 12
Measure Type: Number
Unit of Measure: participants
1 0
Time Frame 4 years
Adverse Event Reporting Description Stratum 1
 
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity with evidence of progression.

Sirolimus oral solution will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment course) with pharmacokinetically-guided dosing. Disease status will be evaluated using volumetric MRI analysis at regular intervals.

Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
All-Cause Mortality
Stratum 1 Stratum 2
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Stratum 1 Stratum 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/46 (43.48%)      4/12 (33.33%)    
Cardiac disorders     
Left Ventricular Systolic Dysfuntion (Grade1) with Admission (Grade 2) * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Gastrointestinal disorders     
Vomiting/Anorexia  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Vomiting  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
AST  1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Diarrhea  1 [2]  0/46 (0.00%)  0 1/12 (8.33%)  1
ALT  1 [2]  0/46 (0.00%)  0 1/12 (8.33%)  1
General disorders     
Pain  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Pain - ABD and Leg * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Infections and infestations     
Infection - Viral  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Fever due to infection - Viral  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Infection with Normal ANC (Pneumonia)  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Infection - UTI (Normal ANC)  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Influenza Virus Type B  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Investigations     
ALT, AST & GGP * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Nervous system disorders     
Headache * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Motor Neuropathy - Paraplegia  1 [3]  1/46 (2.17%)  1 0/12 (0.00%)  0
Hydrocephalus * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Altered Mental State  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Renal and urinary disorders     
Hydroureteronephrosis  1 [4]  0/46 (0.00%)  0 1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders     
ARDS  1 [3]  1/46 (2.17%)  1 0/12 (0.00%)  0
Strep Pneumonia  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Surgical and medical procedures     
Local Complication - Device/Prosthesis (Eye) * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
NF1 Related Planned Surgery * 1 [5]  1/46 (2.17%)  1 0/12 (0.00%)  0
Surgery - Injury to the Musculoskeletal (Lower Extremity) * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Grade 2
[2]
Grade 3
[3]
Grade 4
[4]
Resulting in Increased Creatinine - Grade 3
[5]
Left Distal Femur and Left Proximal Tibid Epiphysiodesis (Unrelated to drug) Grade 3
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Stratum 1 Stratum 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/46 (17.39%)      3/12 (25.00%)    
Ear and labyrinth disorders     
Ear Pain * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Gastrointestinal disorders     
Vomiting  1 [1]  4/46 (8.70%)  4 0/12 (0.00%)  0
Pain - Stomach  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Stomatitis/Mucositis  1 [3]  1/46 (2.17%)  1 0/12 (0.00%)  0
Mucositis  1 [1]  8/46 (17.39%)  8 2/12 (16.67%)  2
Mucositis  1 [2]  2/46 (4.35%)  2 0/12 (0.00%)  0
Constipation  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Mouth Sores  1 [1]  4/46 (8.70%)  4 2/12 (16.67%)  2
Pain -- Adominal  1 [1]  3/46 (6.52%)  3 3/12 (25.00%)  3
Diarrhea  1 [1]  2/46 (4.35%)  2 0/12 (0.00%)  0
Nausea  1 [1]  4/46 (8.70%)  4 1/12 (8.33%)  1
Pain - Throat * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Nausea and Vomiting  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Mouth Sore - Upper Inner Left Corner  1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Heartburn  1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Nausea  1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
General disorders     
Fatigue * 1 [1]  3/46 (6.52%)  3 0/12 (0.00%)  0
Fever * 1 [1]  4/46 (8.70%)  4 1/12 (8.33%)  1
Pain - Leg * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Edema - Knee Swelling * 1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Pain - Knee * 1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Immune system disorders     
Allergic Reaction - Bactrim  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Infections and infestations     
Infection with Normal ANC - Lung  1 [4]  1/46 (2.17%)  1 0/12 (0.00%)  0
Infection -Derm/Skin  1 [5]  1/46 (2.17%)  1 0/12 (0.00%)  0
Infection w/ Normal ANC  1 [1]  2/46 (4.35%)  2 0/12 (0.00%)  0
Infection w/ Normal ANC: Otitis Media  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Pneumonitis * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Infection - Upper Airway NOS  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Otitis - Middle Ear  1 [1]  2/46 (4.35%)  2 0/12 (0.00%)  0
Infection - Ear  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Infection - fever of unknown temperature / Cold  1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Infection - Thrush w/OK ANC  1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Investigations     
Low ANC * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Low WBC * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Low Leukocytes * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Neutropenia * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Neutropoenia * 1 [1]  4/46 (8.70%)  4 0/12 (0.00%)  0
Lymphopenia * 1 [1]  4/46 (8.70%)  4 0/12 (0.00%)  0
Weight Loss * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
ALT * 1 [2]  1/46 (2.17%)  1 1/12 (8.33%)  1
AST * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
GGT * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
WBC * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Lukopenia * 1 [1]  1/46 (2.17%)  1 1/12 (8.33%)  1
Neutropenia * 1 [2]  2/46 (4.35%)  2 0/12 (0.00%)  0
Alanine Aminotransferase Increased * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Leukocytes * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Neutrophils * 1 [1]  5/46 (10.87%)  5 1/12 (8.33%)  1
Neutrophils * 1 [2]  2/46 (4.35%)  2 0/12 (0.00%)  0
Neutrophils/Granulocytes (ANC/AGC) * 1 [1]  4/46 (8.70%)  4 0/12 (0.00%)  0
Neutrophils/Granulocytes Low * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Febrile Neutropenia  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
AST * 1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Low Hemoglobin Delaying Start of Cycle * 1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Metabolism and nutrition disorders     
Anorexia  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Hypercholesteremia  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Decreased Appetite * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Triglycerides - Serum High  1 [1]  2/46 (4.35%)  2 0/12 (0.00%) 
LDL Cholesterol 235MG/DL * 1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Total Cholesterol * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Pain - Back * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Nervous system disorders     
Headache * 1 [1]  2/46 (4.35%)  2 1/12 (8.33%)  1
Hydrocephalus  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Face Tenderness/Swollen/Headaches/Aches * 1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Psychiatric disorders     
Mood Alteration * 1 [1]  2/46 (4.35%)  2 0/12 (0.00%)  0
Mood Alteration - Depression  1 [2]  1/46 (2.17%)  1 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
ARDS (Secondary to RSV)  1 [6]  1/46 (2.17%)  1 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders     
Hirsutism several locations * 1 [7]  1/46 (2.17%)  1 0/12 (0.00%)  0
New Neurofibroma * 1 [8]  1/46 (2.17%)  1 0/12 (0.00%)  0
Rash * 1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
Vascular disorders     
Hypertension  1 [1]  1/46 (2.17%)  1 0/12 (0.00%)  0
High Blood Pressure * 1 [1]  0/46 (0.00%)  0 1/12 (8.33%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Grade 2
[2]
Grade 3
[3]
Grade 1
[4]
Pneumo Grade 3
[5]
Cellulitis Grade 2
[6]
Grade 4
[7]
Legs, Trunk, Back and Face Grade 2
[8]
NF on Back - Grade 2
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Bruce Korf, MD, PhD
Organization: The Univ of Alabama at Birmingham
Phone: 205.934.5140
EMail: kcole@uab.edu
Responsible Party: Bruce Korf, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00634270     History of Changes
Other Study ID Numbers: F071019012
DOD: W81XWH-05-615. ( Other Identifier: Department of Defense )
UAB: 251558. ( Other Identifier: UAB Link Number )
First Submitted: February 20, 2008
First Posted: March 13, 2008
Results First Submitted: July 3, 2015
Results First Posted: February 14, 2017
Last Update Posted: November 17, 2017