Trial Outcomes & Findings for A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis Type 1 Related Plexiform Neurofibromas (NCT NCT00634270)
NCT ID: NCT00634270
Last Updated: 2017-11-17
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
58 participants
Primary outcome timeframe
24 Months Stratum 1
Results posted on
2017-11-17
Participant Flow
Existing and NF1 new patients at Consortium sites and partnering with the Children's Tumor Foundation.
Eligibility for Stratum 1 if evidence of progression and Stratum 2 if not evidence of progression.
Participant milestones
| Measure |
Stratum 1
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
Overall Study
STARTED
|
49
|
13
|
|
Overall Study
COMPLETED
|
46
|
12
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis Type 1 Related Plexiform Neurofibromas
Baseline characteristics by cohort
| Measure |
Stratum 1
n=49 Participants
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
|
Stratum 2
n=13 Participants
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
9 years
n=5 Participants
|
16 years
n=7 Participants
|
10.46 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
35 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reports
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
49 participants
n=5 Participants
|
13 participants
n=7 Participants
|
62 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 Months Stratum 1Population: 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.
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.
Outcome measures
| Measure |
Stratum 1
n=46 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
Time to Disease Progression Based on Volumetric MRI
|
15.4 Months
Interval 14.3 to 23.7
|
—
|
PRIMARY outcome
Timeframe: 48 weeks Stratum 2Population: 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.
Stratum 2 outcome - Response
Outcome measures
| Measure |
Stratum 1
n=12 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
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
|
12 participants
|
—
|
PRIMARY outcome
Timeframe: 24 weeks Stratum 1 / 48 weeks Stratum 2Population: All evaluable participants for Stratum 1 and 2 combined.
Number of participants experiencing adverse events
Outcome measures
| Measure |
Stratum 1
n=49 Participants
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
|
Stratum 2
n=13 Participants
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
Toxicity
|
49 Participants
|
13 Participants
|
PRIMARY outcome
Timeframe: 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 hoursPopulation: 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.
An iterative 2-stage Bayesian method was used for the PK parameter analyses
Outcome measures
| Measure |
Stratum 1
n=44 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
To Characterize the Pharmacokinetic Profile of Sirolimus Administered to This Patient Population (Clearance Liters/Hour (L/h))
|
11.8 Clearance liters/hour (L/h)
Standard Deviation 4.6
|
—
|
PRIMARY outcome
Timeframe: 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 hoursPopulation: 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.
An iterative 2-stage Bayesian method was used for the PK parameter analyses
Outcome measures
| Measure |
Stratum 1
n=44 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
To Characterize the Pharmacokinetic Profile of Sirolimus When Administered to This Patient Population Using Liters/Hour Per Population Median Weight of 70kg (L/h70kg)
|
23.7 L/h/70kg
Standard Deviation 6.7
|
—
|
PRIMARY outcome
Timeframe: 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 hoursPopulation: 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.
An iterative 2-stage Bayesian Method was used for the PK parameter analyses
Outcome measures
| Measure |
Stratum 1
n=44 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
To Characterize the Pharmacokinetic Profile of Sirolimus When Administered to This Patient Population - (Clearance (L/h Per 1.85 m^2)
|
6.4 L/h per 1.85 m^2
Standard Deviation 2.5
|
—
|
PRIMARY outcome
Timeframe: 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 hoursPopulation: 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.
An iterative 2-stage Bayesian Method was used for the PK parameter analyses
Outcome measures
| Measure |
Stratum 1
n=44 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
To Characterize the Pharmacokinetic Profile of Sirolimus When Administered to This Patient Population- Therapeutic Dose (mg/m^2 Per Dose)
|
2.0 Therapeutic Dose mg/m^2 per dose
Standard Deviation 0.7
|
—
|
PRIMARY outcome
Timeframe: 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 hoursPopulation: 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.
An iterative 2-stage Bayesian Method was used for the PK parameter analyses
Outcome measures
| Measure |
Stratum 1
n=44 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
To Characterize the Pharmacokinetic Profile of Sirolimus in When Administered to This Patient Population - Therapeutic Dose (mg/kg Per Dose)
|
0.08 Therapeutic Dose (mg/kg per dose)
Standard Deviation 0.04
|
—
|
PRIMARY outcome
Timeframe: 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 hoursPopulation: 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.
An iterative 2-stage Bayesian method was used for the PK parameter analyses
Outcome measures
| Measure |
Stratum 1
n=44 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
To Characterize the Pharmacokinetic Profile of Sirolimus When Administered to This Patient Population - Therapeutic Dose (mg/kg)^0.75
|
0.14 Therapeutic Dose (mg/kg)^0.75
Standard Deviation 0.05
|
—
|
SECONDARY outcome
Timeframe: 24 weeks Stratum 1 / 48 weeks Stratum 2Population: 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.
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.
Outcome measures
| Measure |
Stratum 1
n=23 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
To Evaluate the Quality of Life During Treatment With Sirolimus by Assessing Preliminary Correlations of Response With Quality-of-life Outcomes
|
2.8 Units on a scale
Standard Deviation 9.59
|
—
|
SECONDARY outcome
Timeframe: 24 weeks Stratum 1 / 48 weeks Stratum 2Population: 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
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 weeks Stratum 1 / 48 weeks Stratum 2Population: Samples were inadequate in quantity to allow for this analysis.
Response by Volumetric MRI.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 weeks Stratum 1 / 48 weeks Stratum 2There were no data collected for this outcome measure.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 weeks Stratum 1 OnlyPopulation: Subjects in Stratum 1.
Trough concentration of sirolimus is reported in nanograms per mL.
Outcome measures
| Measure |
Stratum 1
n=37 Participants
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
|
Stratum 2
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
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.
|
9.37 ng/mL
Standard Deviation 2.48
|
—
|
SECONDARY outcome
Timeframe: 24 weeks Stratum 1 / 48 weeks Stratum 2Number of patients who experienced hyperlipidemia is being reported.
Outcome measures
| Measure |
Stratum 1
n=46 Participants
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
|
Stratum 2
n=12 Participants
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
To Evaluate the Role of Apolipoprotein E Genotypes as Predictors for Development of Hyperlipidemia During Therapy With Sirolimus.
|
1 participants
|
0 participants
|
Adverse Events
Stratum 1
Serious events: 20 serious events
Other events: 8 other events
Deaths: 0 deaths
Stratum 2
Serious events: 4 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Stratum 1
n=46 participants at risk
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.
|
Stratum 2
n=12 participants at risk
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
Gastrointestinal disorders
Vomiting/Anorexia
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Nervous system disorders
Headache
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection - Viral
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
ALT, AST & GGP
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Fever due to infection - Viral
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Surgical and medical procedures
Local Complication - Device/Prosthesis (Eye)
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection with Normal ANC (Pneumonia)
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Cardiac disorders
Left Ventricular Systolic Dysfuntion (Grade1) with Admission (Grade 2)
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
General disorders
Pain
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Nervous system disorders
Motor Neuropathy - Paraplegia
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection - UTI (Normal ANC)
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Respiratory, thoracic and mediastinal disorders
ARDS
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Surgical and medical procedures
NF1 Related Planned Surgery
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Surgical and medical procedures
Surgery - Injury to the Musculoskeletal (Lower Extremity)
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Nervous system disorders
Hydrocephalus
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Nervous system disorders
Altered Mental State
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Respiratory, thoracic and mediastinal disorders
Strep Pneumonia
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Influenza Virus Type B
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
General disorders
Pain - ABD and Leg
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
AST
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
ALT
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Renal and urinary disorders
Hydroureteronephrosis
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
Other adverse events
| Measure |
Stratum 1
n=46 participants at risk
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.
|
Stratum 2
n=12 participants at risk
Non-randomized, single arm interventional strata for inoperable Plexiform Neurofibromas with potential to cause significant morbidity WITHOUT evidence of progression
|
|---|---|---|
|
Nervous system disorders
Headache
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Vomiting
|
8.7%
4/46 • Number of events 4 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Low ANC
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Low WBC
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Pain - Stomach
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Low Leukocytes
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Stomatitis/Mucositis
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Neutropenia
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Neutropoenia
|
8.7%
4/46 • Number of events 4 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Mucositis
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Lymphopenia
|
8.7%
4/46 • Number of events 4 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Ear and labyrinth disorders
Ear Pain
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Constipation
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Mouth Sores
|
8.7%
4/46 • Number of events 4 • 4 years
Stratum 1
|
16.7%
2/12 • Number of events 2 • 4 years
Stratum 1
|
|
Investigations
Weight Loss
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Metabolism and nutrition disorders
Anorexia
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Pain -- Adominal
|
6.5%
3/46 • Number of events 3 • 4 years
Stratum 1
|
25.0%
3/12 • Number of events 3 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Diarrhea
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Metabolism and nutrition disorders
Hypercholesteremia
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
General disorders
Fatigue
|
6.5%
3/46 • Number of events 3 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
General disorders
Fever
|
8.7%
4/46 • Number of events 4 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Psychiatric disorders
Mood Alteration
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
ALT
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Investigations
AST
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Investigations
GGT
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
WBC
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Lukopenia
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Immune system disorders
Allergic Reaction - Bactrim
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Skin and subcutaneous tissue disorders
Hirsutism several locations
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Skin and subcutaneous tissue disorders
New Neurofibroma
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Alanine Aminotransferase Increased
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection with Normal ANC - Lung
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Psychiatric disorders
Mood Alteration - Depression
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection -Derm/Skin
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection w/ Normal ANC
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection w/ Normal ANC: Otitis Media
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Leukocytes
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Neutrophils
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Pain - Throat
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Pneumonitis
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Respiratory, thoracic and mediastinal disorders
ARDS (Secondary to RSV)
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Metabolism and nutrition disorders
Triglycerides - Serum High
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Vascular disorders
Hypertension
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Metabolism and nutrition disorders
LDL Cholesterol 235MG/DL
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Metabolism and nutrition disorders
Total Cholesterol
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Musculoskeletal and connective tissue disorders
Pain - Back
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Neutrophils/Granulocytes (ANC/AGC)
|
8.7%
4/46 • Number of events 4 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection - Upper Airway NOS
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Neutrophils/Granulocytes Low
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Nausea and Vomiting
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Nervous system disorders
Hydrocephalus
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Otitis - Middle Ear
|
4.3%
2/46 • Number of events 2 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
General disorders
Pain - Leg
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Investigations
Febrile Neutropenia
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Infections and infestations
Infection - Ear
|
2.2%
1/46 • Number of events 1 • 4 years
Stratum 1
|
0.00%
0/12 • 4 years
Stratum 1
|
|
Nervous system disorders
Face Tenderness/Swollen/Headaches/Aches
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Infections and infestations
Infection - fever of unknown temperature / Cold
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Vascular disorders
High Blood Pressure
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Mouth Sore - Upper Inner Left Corner
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Gastrointestinal disorders
Heartburn
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
General disorders
Edema - Knee Swelling
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
General disorders
Pain - Knee
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Investigations
Low Hemoglobin Delaying Start of Cycle
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
|
Infections and infestations
Infection - Thrush w/OK ANC
|
0.00%
0/46 • 4 years
Stratum 1
|
8.3%
1/12 • Number of events 1 • 4 years
Stratum 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place