Recurrent Glioblastoma or Other Glioma Subtypes
Conditions
Keywords
BGJ398,, recurrent glioblastoma', recurrent GBM,, FGFR,
Brief summary
This is an open-label non-randomized, multicenter, phase II study of BGJ398 administered to adult patients with histologically confirmed GBM and/or other glioma subtypes with FGFR1-TACC1, FGFR3-TACC3 fusion and/or activating mutation in FGFR1, 2 or 3.
Detailed description
Patients were enrolled in two groups. Group 1 enrolled patients who are not candidates for surgery. Group 2 was planned to enroll patients who are surgical candidates. Patients from both groups were evaluated for tumor response and progression by MRI every 8 weeks until disease progression or discontinuation from study using RANO criteria.
Interventions
DRUGBGJ398
Capsule for oral use.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with histologically confirmed GBM and/or other glioma subtypes at the time of diagnosis or prior relapse. 2. Written documentation of local or central laboratory determination of amplification or translocation to FGFR1-TACC1, FGFR3-TACC-3 fusion and/or activating mutation in FGFR1, FGFR2,or FGFR3 3. RANO defined tumor progression by MRI in comparison to a prior scan 4. Patients must have received prior external beam radiotherapy and temozolomide.
Exclusion criteria
1. History of another primary malignancy 2. Prior or current treatment with a FGFR inhibitor 3. Neurological symptoms related to underlying disease requiring increasing doses of corticosteroids 4. Patients must not be taking Enzyme Inducing Anti-Epileptic Drug (EIAED). If previously on an EIAED, the patient must be off of it for at least two weeks prior to study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 6 months | To assess the anti-tumor activity of BGJ398 for patients with GBM and/or other glioma subtypes that harbor FGFR1-TACC1, FGFR3-TACC3 fusion and/or activating mutation in FGFR1, 2 or 3 based on PFS6 (PFS rate at 6 months as defined by RANO criteria as assessed by the investigator) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 5 years | To further assess the anti-tumor activity of BGJ398 for patients with GBM with an amplification, translocation, or activating mutation in FGFR1,2,3 or 4, based on Objective Response Rate (ORR - patients with measurable disease - as defined by RANO criteria as assessed by the investigator |
| Overall Survival | 5 years | To further assess the anti-tumor activity of BGJ398 for patients with GBM and/or other glioma subtypes that harbor FGFR1-TACC1, FGFR3-TACC3 fusion and/or activating mutation in FGFR1, 2 and 3 based on Overall Survival |
| Safety and Tolerability | 5 years | Safety: type, frequency, and severity of AEs and SAEs; Tolerability: dose interruptions, reductions and dose intensity, and evaluations of laboratory values |
Countries
Australia, Belgium, Netherlands, Spain, Switzerland, United States
Participant flow
Recruitment details
All 26 patients included were enrolled in the non-Surgical group, and were treated with BGJ398 125 mg once daily in 28-day cycles, on a 3 weeks on/1 week off schedule (dosing days 1 to 21 of every 28-day cycle). No patients were enrolled in the surgical group.
Pre-assignment details
Patients were planned to be enrolled in two groups: Group 1 (non-surgical group) targeted patients with response assessment in neuro-oncology (RANO) defined tumor progression not eligible for surgical resection. Group 2 (surgical group) targeted patients with recurrent disease eligible for cytoreductive surgery.
Participants by arm
| Arm | Count |
|---|---|
| BGJ398X 125 mg BGJ398 non surgical | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 23 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | BGJ398X |
|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 13.59 |
| Race/Ethnicity, Customized caucasian | 26 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 26 |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 9 / 26 |
Outcome results
Primary
Progression Free Survival
To assess the anti-tumor activity of BGJ398 for patients with GBM and/or other glioma subtypes that harbor FGFR1-TACC1, FGFR3-TACC3 fusion and/or activating mutation in FGFR1, 2 or 3 based on PFS6 (PFS rate at 6 months as defined by RANO criteria as assessed by the investigator)
Time frame: 6 months
Population: full analysis set, patients censored
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BGJ398X | Progression Free Survival | 1.7 months |
Secondary
Overall Response Rate
To further assess the anti-tumor activity of BGJ398 for patients with GBM with an amplification, translocation, or activating mutation in FGFR1,2,3 or 4, based on Objective Response Rate (ORR - patients with measurable disease - as defined by RANO criteria as assessed by the investigator
Time frame: 5 years
Population: full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGJ398X | Overall Response Rate | partial response | 2 Participants |
| BGJ398X | Overall Response Rate | stable disease | 7 Participants |
| BGJ398X | Overall Response Rate | progressive disease | 13 Participants |
| BGJ398X | Overall Response Rate | unknown | 3 Participants |
| BGJ398X | Overall Response Rate | missing | 1 Participants |
Secondary
Overall Survival
To further assess the anti-tumor activity of BGJ398 for patients with GBM and/or other glioma subtypes that harbor FGFR1-TACC1, FGFR3-TACC3 fusion and/or activating mutation in FGFR1, 2 and 3 based on Overall Survival
Time frame: 5 years
Population: full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BGJ398X | Overall Survival | 6.74 months |
Secondary
Safety and Tolerability
Safety: type, frequency, and severity of AEs and SAEs; Tolerability: dose interruptions, reductions and dose intensity, and evaluations of laboratory values
Time frame: 5 years
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGJ398X | Safety and Tolerability | participants with dose interruptions | 13 Participants |
| BGJ398X | Safety and Tolerability | participants with dose reductions | 4 Participants |