Medulloblastoma
Conditions
Keywords
medulloblastoma,, relapsed,, pediatric,, children,, adults,, Hh pathway inhibitor,, LDE225
Brief summary
This Phase II study evaluated the safety and efficacy of LDE225 in adult and pediatric patients with Hh-pathway activated, relapsed MB.
Detailed description
This study was a single-arm study of the efficacy and safety of oral sonidegib in patients with Hh-pathway activated relapsed medulloblastoma. It was initially designed as a randomized, controlled, open-label phase III study of adults and children with Hh-pathway activated MB whose disease had failed standard of care therapy, including radiation therapy (RT). The original study consisted of a randomized controlled part and a non-randomized uncontrolled part. Approximately 69 patients were to be randomized in a 2:1 ratio to receive sonidegib oral suspension or the active control, temozolomide (TMZ) capsules. Randomization was to be stratified according to age, \<18 years versus ≥ 18 years. Approximately 40 patients were to receive sonidegib in the non-randomized uncontrolled part of the study. Following the enrollment of 11 patients, the study was amended to become a phase II single-arm study with only sonidegib, and the target enrollment was changed to 20 patients. Prior to the study amendment, TMZ participants whose disease progressed while on TMZ were permitted to crossover to sonidegib. After the amendment, participants receiving TMZ were crossed over to sonidegib.
Interventions
DRUGLDE225
Sonidegib for oral suspension was supplied in amber glass bottles. Sonidegib oral suspension was combined with the supplied reconstitution vehicle to a final concentration of 50 mg/mL.
DRUGTMZ
Temozolomide capsules were obtained locally by the Investigator
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically confirmed diagnosis of MB, who have experienced relapse or progression after standard-of-care therapy including radiotherapy. Patients currently receiving steroids must have been on a stable (or decreasing) dose for at least 5 days before initiating study therapy. * Only patients with a test result, using the 5-gene Hh signature assay, indicating Hhpathway activated MB are eligible for this study. All available tumor material obtained at any time during the course of the patient's disease should be submitted for these analyses * At least one measurable lesion defined as lesion(s) that can be accurately measured in at least two dimensions and is ≥ 10 mm in each dimension by Gadolinium (Gd)-MRI, irrespective of slice thickness/reconstruction interval, for CNS lesions and CT or MRI (with or without contrast) for non-CNS lesions. All patients with CNS lesions must have a brain MRI with and without gadolinium and a spine MRI with gadolinium within 2 weeks prior to first dose of study treatment. * Performance Status corresponding to ECOG score of 0, 1, or 2: 1. Karnofsky performance status score ≥ 50 for patients \>16 years of age 2. Lansky performance status score ≥ 50 for patients ≤ 16 years of age * Adequate bone marrow function as defined as: 1. Peripheral absolute neutrophil count (ANC) ≥ 1.5 x 109/L 2. Platelet count ≥ 80 x 109/L 3. Hemoglobin (Hgb) ≥ 9 g/dL * Serum CK ≤1.5 ULN
Exclusion criteria
* Prior treatment with a Smoothened inhibitor Systemic anticancer treatment within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies). * Focal radiation therapy within 4 weeks before first dose of study treatment, or full spinal radiotherapy within 3 months before first dose of study treatment. * Patients who have neuromuscular disorders that are associated with elevated CK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). * Patients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 or are metabolized by CYP2B6 and CYP2C9, that have narrow therapeutic indices that cannot be discontinued at least 2 weeks before first dose of study treatment and for the duration of the study * Patients receiving unstable or increasing doses of corticosteroids. If patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms, dose must have been stabilized (or decreasing) for at least 5 days before first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 | ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). Assessments after crossover were not included for TMZ participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 | PFS was defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause. PFS was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. |
| Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 | ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). ORR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. Assessments after crossover were not included for TMZ patients. |
| Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 | PFS was defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). TMZ participants without event prior to crossover were censored. |
| Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 | OS was defined as the time from date of randomization to date of death due to any cause. All deaths are considered, including deaths occurred after crossover for TMZ participants. |
| Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49 and 53 | Blood samples were collected for assessment. The children's group was analyzed up until week 25 only. |
| Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 | DoR was defined as the time from the first documented onset of confirmed PR or CR to the date of PD/relapse or death due to medulloblastoma. DoR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. TMZ participants without an event prior to crossover were censored. |
Countries
Australia, Brazil, Canada, France, Germany, Italy, Netherlands, Russia, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Pre-assignment details
Analyses were performed by treatment and by age group.
Participants by arm
| Arm | Count |
|---|---|
| Sonidegib (LDE225) Children 500 mg/m2 orally | 2 |
| Sonidegib (LDE225) Adults 600 mg orally | 16 |
| Temozolomide (TMZ) 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. | 4 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Period | Adverse Event | 0 | 1 | 0 |
| Treatment Period | Death | 0 | 0 | 1 |
| Treatment Period | Progressive disease | 0 | 1 | 0 |
| Treatment Period | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) | Total |
|---|---|---|---|---|
| Age, Continuous | 8.5 Years FULL_RANGE 6.36 | 37.0 Years FULL_RANGE 8.17 | 35.5 Years FULL_RANGE 3.16 | 35.0 Years FULL_RANGE 10.73 |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 11 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 16 / 16 | 18 / 18 | 4 / 4 |
| serious Total, serious adverse events | 2 / 2 | 9 / 16 | 11 / 18 | 1 / 4 |
Outcome results
Primary
Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). Assessments after crossover were not included for TMZ participants.
Time frame: from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Population: The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sonidegib (LDE225) Children | Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 0.0 Percentage of participants |
| Sonidegib (LDE225) Adults | Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 18.8 Percentage of participants |
| Temozolomide (TMZ) | Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 0.0 Percentage of participants |
Secondary
Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
DoR was defined as the time from the first documented onset of confirmed PR or CR to the date of PD/relapse or death due to medulloblastoma. DoR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. TMZ participants without an event prior to crossover were censored.
Time frame: from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Population: The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sonidegib (LDE225) Children | Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | NA months |
| Sonidegib (LDE225) Adults | Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 8.5 months |
| Temozolomide (TMZ) | Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | NA months |
Secondary
Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
OS was defined as the time from date of randomization to date of death due to any cause. All deaths are considered, including deaths occurred after crossover for TMZ participants.
Time frame: from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Population: The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sonidegib (LDE225) Children | Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | NA months |
| Sonidegib (LDE225) Adults | Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 9.5 months |
| Temozolomide (TMZ) | Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | NA months |
Secondary
Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). ORR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. Assessments after crossover were not included for TMZ patients.
Time frame: from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Population: The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sonidegib (LDE225) Children | Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 0.0 Percentage of participants |
| Sonidegib (LDE225) Adults | Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 25.0 Percentage of participants |
| Temozolomide (TMZ) | Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 0.0 Percentage of participants |
Secondary
PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
PFS was defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause. PFS was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma.
Time frame: from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Population: The FAS was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sonidegib (LDE225) Children | PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | NA months |
| Sonidegib (LDE225) Adults | PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 3.3 months |
| Temozolomide (TMZ) | PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 2.9 months |
Secondary
Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225)
Blood samples were collected for assessment. The children's group was analyzed up until week 25 only.
Time frame: Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49 and 53
Population: The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 1 (n=2,11) | 0.00 ng/mL | Standard Deviation 0 |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 3 (n=2,10) | 2890 ng/mL | Standard Deviation 1240 |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 5 (n=2,8) | 4930 ng/mL | Standard Deviation 1380 |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 7 (n=1,8) | 2810 ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 9 (n=1,8) | 4670 ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 13 (n=1,4) | 3680 ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 17 (n=1,6) | 3060 ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 21 (n=1,5) | 3770 ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 25 (n=1,4) | 1890 ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 29 (n=NA,4) | NA ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 33 (n=NA,4) | NA ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 37 (n=NA,3) | NA ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 41 (n=NA,4) | NA ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 45 (n=NA,2) | NA ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 49 (n=NA,2) | NA ng/mL | — |
| Sonidegib (LDE225) Children | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 53 (n=NA,2) | NA ng/mL | — |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 53 (n=NA,2) | 2080 ng/mL | Standard Deviation 764 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 1 (n=2,11) | 0.00 ng/mL | Standard Deviation 0 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 25 (n=1,4) | 2050 ng/mL | Standard Deviation 625 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 3 (n=2,10) | 761 ng/mL | Standard Deviation 519 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 41 (n=NA,4) | 2370 ng/mL | Standard Deviation 916 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 5 (n=2,8) | 1090 ng/mL | Standard Deviation 700 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 29 (n=NA,4) | 2050 ng/mL | Standard Deviation 906 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 7 (n=1,8) | 1450 ng/mL | Standard Deviation 842 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 49 (n=NA,2) | 2330 ng/mL | Standard Deviation 990 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 9 (n=1,8) | 1530 ng/mL | Standard Deviation 682 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 33 (n=NA,4) | 2180 ng/mL | Standard Deviation 512 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 13 (n=1,4) | 2330 ng/mL | Standard Deviation 1100 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 45 (n=NA,2) | 2890 ng/mL | Standard Deviation 290 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 17 (n=1,6) | 1880 ng/mL | Standard Deviation 730 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 37 (n=NA,3) | 2850 ng/mL | Standard Deviation 306 |
| Sonidegib (LDE225) Adults | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) | Week 21 (n=1,5) | 2270 ng/mL | Standard Deviation 915 |
Secondary
Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
PFS was defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). TMZ participants without event prior to crossover were censored.
Time frame: from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Population: The FAS was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sonidegib (LDE225) Children | Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 1.6 months |
| Sonidegib (LDE225) Adults | Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 3.3 months |
| Temozolomide (TMZ) | Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 | 2.9 months |