Trial Outcomes & Findings for Efficacy and Safety of RAD001 in Treating Plexiform Neurofibromas (PN) Associated With Neurofibromatosis (NF1) (NCT NCT01365468)
NCT ID: NCT01365468
Last Updated: 2016-05-12
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
9 participants
Primary outcome timeframe
Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days)
Results posted on
2016-05-12
Participant Flow
Participant milestones
| Measure |
Stratum 1
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity with documented progressive PN prior to study entry wereenrolled in this stratum. 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.
|
Stratum 2
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity that do not have documented progression of the PN at the time of study entry were enrolled in this stratum. 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.
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
5
|
|
Overall Study
COMPLETED
|
0
|
5
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
| Measure |
Stratum 1
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity with documented progressive PN prior to study entry wereenrolled in this stratum. 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.
|
Stratum 2
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity that do not have documented progression of the PN at the time of study entry were enrolled in this stratum. 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.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Disease progression
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
Baseline Characteristics
Efficacy and Safety of RAD001 in Treating Plexiform Neurofibromas (PN) Associated With Neurofibromatosis (NF1)
Baseline characteristics by cohort
| Measure |
Stratum 1
n=4 Participants
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity with documented progressive PN prior to study entry wereenrolled in this stratum. 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.
|
Stratum 2
n=5 Participants
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity that do not have documented progression of the PN at the time of study entry were enrolled in this stratum. 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.
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
22.7 Years
STANDARD_DEVIATION 14.3 • n=5 Participants
|
16.9 Years
STANDARD_DEVIATION 9.8 • n=7 Participants
|
19.5 Years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days)Population: The Full Analysis Set (FAS) consisted of all enrolled patients.
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.
Outcome measures
| Measure |
Stratum 1
n=4 Participants
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity with documented progressive PN prior to study entry wereenrolled in this stratum. 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.
|
Stratum 2
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity that do not have documented progression of the PN at the time of study entry were enrolled in this stratum. 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.
|
|---|---|---|
|
Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only)
|
NA Days
Median was not achieved because only one progression event occurred.
|
—
|
PRIMARY outcome
Timeframe: Screening, after course #6, then every 6 months and end of treatment(1 course=28days)Population: The Full Analysis Set (FAS) consisted of all enrolled patients.
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.
Outcome measures
| Measure |
Stratum 1
n=5 Participants
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity with documented progressive PN prior to study entry wereenrolled in this stratum. 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.
|
Stratum 2
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity that do not have documented progression of the PN at the time of study entry were enrolled in this stratum. 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.
|
|---|---|---|
|
Number of Patients With Objective Radiographic Responses Based on Volumetric MRI Measurements (In Stratum 2 Only)
Complete Response
|
0 Patients
|
—
|
|
Number of Patients With Objective Radiographic Responses Based on Volumetric MRI Measurements (In Stratum 2 Only)
Partial Response
|
0 Patients
|
—
|
|
Number of Patients With Objective Radiographic Responses Based on Volumetric MRI Measurements (In Stratum 2 Only)
Stable Disease
|
5 Patients
|
—
|
PRIMARY outcome
Timeframe: From the time ICF was signed until 28 days after End of Treatment (up to a maximum of 25 months)Population: The Safety Population consisted of all patients who received at least one dose of study treatment and had at least one post-baseline safety assessment.
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.
Outcome measures
| Measure |
Stratum 1
n=4 Participants
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity with documented progressive PN prior to study entry wereenrolled in this stratum. 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.
|
Stratum 2
n=5 Participants
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity that do not have documented progression of the PN at the time of study entry were enrolled in this stratum. 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.
|
|---|---|---|
|
Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04
At least one Grade 2 AE
|
4 Patients
|
5 Patients
|
|
Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04
At least one Grade 4 AE
|
1 Patients
|
0 Patients
|
|
Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04
At least one Grade 3 AE
|
1 Patients
|
0 Patients
|
|
Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04
At least one Grade 1 AE
|
4 Patients
|
5 Patients
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening, Day 1, after course #3, #6, #12, #18, #24, End of Treatment (1 course = 28 days)Population: Study got terminated because of poor patient's accrual. Enrolled patients were less than planned number of patients required for analysis. Hence, planned analysis was not done.
Clinical response is defined as improvement of function, performance status, or decrease in PN related pain persisting for at least 28 days on treatment.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening, after course #3, #6, #12, #18, #24, End of Treatment (1 course = 28 days)Population: Study got terminated because of poor patient's accrual. Enrolled patients were less than planned number of patients required for analysis. Hence, planned analysis was not done.
The Physician"s Global Assessment of Clinical Condition (PGA) is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the patient"s skin disease as compared to baseline. Responses must be confirmed by at least two assessments separated in time by at least 4 weeks. The grading ranges from 0 to 6; 0 is Completely clear where as 6 is for worse condition. A complete clinical response (CCR) requires a grading of 0 indicating the absence of disease (histological confirmation is not required). Grades 1, 2, and 3 constitute partial response, indicating improvement of at least 50 percent, but less than 100 percent improvement.
Outcome measures
Outcome data not reported
Adverse Events
Stratum 1
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Stratum 2
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Stratum 1
n=4 participants at risk
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity with documented progressive PN prior to study entry wereenrolled in this stratum. 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.
|
Stratum 2
n=5 participants at risk
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity that do not have documented progression of the PN at the time of study entry were enrolled in this stratum. 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.
|
|---|---|---|
|
Immune system disorders
Hypersensitivity
|
25.0%
1/4
|
0.00%
0/5
|
Other adverse events
| Measure |
Stratum 1
n=4 participants at risk
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity with documented progressive PN prior to study entry wereenrolled in this stratum. 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.
|
Stratum 2
n=5 participants at risk
Adults and children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) with the potential to cause significant morbidity that do not have documented progression of the PN at the time of study entry were enrolled in this stratum. 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.
|
|---|---|---|
|
Ear and labyrinth disorders
Ear pain
|
50.0%
2/4
|
0.00%
0/5
|
|
Ear and labyrinth disorders
External ear inflammation
|
0.00%
0/4
|
20.0%
1/5
|
|
Eye disorders
Ocular hyperaemia
|
25.0%
1/4
|
0.00%
0/5
|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4
|
40.0%
2/5
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
2/4
|
0.00%
0/5
|
|
Gastrointestinal disorders
Dysphagia
|
50.0%
2/4
|
0.00%
0/5
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/4
|
20.0%
1/5
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/4
|
20.0%
1/5
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4
|
0.00%
0/5
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/4
|
20.0%
1/5
|
|
Gastrointestinal disorders
Toothache
|
25.0%
1/4
|
20.0%
1/5
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4
|
20.0%
1/5
|
|
General disorders
Asthenia
|
0.00%
0/4
|
20.0%
1/5
|
|
General disorders
Chest pain
|
25.0%
1/4
|
0.00%
0/5
|
|
General disorders
Discomfort
|
25.0%
1/4
|
0.00%
0/5
|
|
General disorders
Fatigue
|
50.0%
2/4
|
40.0%
2/5
|
|
General disorders
Influenza like illness
|
75.0%
3/4
|
20.0%
1/5
|
|
General disorders
Mucosal inflammation
|
50.0%
2/4
|
40.0%
2/5
|
|
General disorders
Oedema peripheral
|
25.0%
1/4
|
0.00%
0/5
|
|
General disorders
Pain
|
25.0%
1/4
|
20.0%
1/5
|
|
General disorders
Peripheral swelling
|
25.0%
1/4
|
0.00%
0/5
|
|
Infections and infestations
Eye infection
|
0.00%
0/4
|
20.0%
1/5
|
|
Infections and infestations
Pneumonia
|
0.00%
0/4
|
20.0%
1/5
|
|
Infections and infestations
Skin infection
|
0.00%
0/4
|
20.0%
1/5
|
|
Injury, poisoning and procedural complications
Tendonitis
|
25.0%
1/4
|
0.00%
0/5
|
|
Investigations
Blood cholesterol increased
|
25.0%
1/4
|
40.0%
2/5
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/4
|
20.0%
1/5
|
|
Investigations
Blood triglycerides increased
|
25.0%
1/4
|
20.0%
1/5
|
|
Investigations
Drug level increased
|
25.0%
1/4
|
0.00%
0/5
|
|
Investigations
Eosinophil count increased
|
0.00%
0/4
|
20.0%
1/5
|
|
Investigations
Low density lipoprotein increased
|
25.0%
1/4
|
0.00%
0/5
|
|
Investigations
Lymphocyte count decreased
|
25.0%
1/4
|
0.00%
0/5
|
|
Investigations
Platelet count decreased
|
25.0%
1/4
|
20.0%
1/5
|
|
Metabolism and nutrition disorders
Decreased appetite
|
25.0%
1/4
|
20.0%
1/5
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
25.0%
1/4
|
20.0%
1/5
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
25.0%
1/4
|
0.00%
0/5
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
50.0%
2/4
|
0.00%
0/5
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroma
|
25.0%
1/4
|
0.00%
0/5
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4
|
20.0%
1/5
|
|
Nervous system disorders
Headache
|
75.0%
3/4
|
80.0%
4/5
|
|
Nervous system disorders
Paraesthesia
|
25.0%
1/4
|
0.00%
0/5
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/4
|
20.0%
1/5
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/4
|
20.0%
1/5
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/4
|
20.0%
1/5
|
|
Psychiatric disorders
Tic
|
25.0%
1/4
|
0.00%
0/5
|
|
Reproductive system and breast disorders
Breast mass
|
25.0%
1/4
|
0.00%
0/5
|
|
Reproductive system and breast disorders
Metrorrhagia
|
25.0%
1/4
|
0.00%
0/5
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
25.0%
1/4
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/4
|
20.0%
1/5
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
25.0%
1/4
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
25.0%
1/4
|
40.0%
2/5
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
|
25.0%
1/4
|
0.00%
0/5
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/4
|
20.0%
1/5
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/4
|
20.0%
1/5
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
2/4
|
0.00%
0/5
|
|
Surgical and medical procedures
Cytoreductive surgery
|
0.00%
0/4
|
20.0%
1/5
|
|
Surgical and medical procedures
Tooth extraction
|
0.00%
0/4
|
20.0%
1/5
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER