Ignite Creation Date:
2025-12-25 @ 3:02 AM
Ignite Modification Date:
2026-01-08 @ 10:08 PM
Study NCT ID:
NCT02824133
Status:
COMPLETED
Last Update Posted:
2019-05-29
First Post:
2015-12-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Treatment With AZD4547 for Recurrent Malignant Glioma Expressing FGFR-TACC Gene Fusion"
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Study Overview
Official Title:
A Phase I/II, Open-Label, Multicentre Study to Assess The Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of AZD4547 in Patients With Relapsed/Refractory Glioma Positive for an FGFR Fusion
Status:
COMPLETED
Status Verified Date:
2019-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TARGET
Brief Summary:
The investigators will look for the presence of the fusion gene in all patients operated on for glioma. This search will be limited to all gliomas that show no IDH1 mutation, the latter being sought in both routine and anomalies never co-existing.
The hypothesis is that the rate of progression-free survival in grade IV gliomas and III without IDH1 mutation, with the usual chemotherapy, only 15% at 6 months (ie, 85% of patients relapse before 6 months of treatment), must be with this new treatment 35% (primary endpoint).
The main objective is the evaluation of disease-free survival at 6 months.
The hypothesis is that the rate of progression-free survival in grade IV gliomas and III without IDH1 mutation, with the usual chemotherapy, only 15% at 6 months (ie, 85% of patients relapse before 6 months of treatment), must be with this new treatment 35% (primary endpoint).
The main objective is the evaluation of disease-free survival at 6 months.
Detailed Description:
3% of GBM and IDHwt gliomas have a highly oncogenic FGFR-TACC gene fusion that confers high sensitivity to FGFR inhibitors to tumor cells, in vitro and in vivo. Preclinical data shows that expression of FGFR-TACC fusions confers sensitivity to FGFR inhibitors (including AZD4547) to GBM models.AZD4547 (AstraZeneca) is a potent and selective inhibitor of FGFR-1, 2 and 3 receptor tyrosine kinases. Preclinical data have shown some CNS penetration. Some of the important adverse events are hyperphosphatemia, and ocular complications. The primary objective and assessment criterion is to assess the efficacy of AZD4547 by measuring the rate of Progression Free Survival at 6 months (PFS6) in recurrent malignant glioma patients with FGFR-TACC fusion.Secondary objectives and assessment criteria are: - To characterize the safety, tolerability and PK of AZD4547 in glioma patients
* To further assess the anti-tumor activity of AZD4547 for patients with recurrent glioma with FGFR-TACC fusion based on Overall Response Rate for patients with a measurable residue.
* To further assess the anti-tumor activity of AZD4547 for patients with recurrent glioma with FGFR-TACC fusion based on the duration of PFS
* To further assess the anti-tumor activity of AZD4547 for patients with recurrent glioma with a FGFR-TACC fusion based on Overall Survival AZD4547 Exploratory objectives - To elucidate the mechanism of response and resistance (primary and secondary) by exploratory biomarker analysis Experimental design: This is a phase II study in patients diagnosed with a FGFR3-TACC3 or FGFR1-TACC1 fusion positive glioma presenting with a recurrence of the disease after chemotherapy and radiotherapy. RNA will be systematically screened for the presence of FGFR-TACC in each of the 11 participating centers, and IHC for FGFR3 hyperexpression. The investigators also encourage a wide use of FGFR3 IHC in non participating centers in order to identify additional potential candidates who can be referred to one of the 11 centers for assessment of FGFR-TACC expression by RNA analysis..
Patients will receive AZD4547 at a dose of 80mg bd on a continuous schedule, until disease progression. With the following hypothesis: P0: PFS6=15%, P1: PFS6=35%, with alpha=5% and power=80%, an initial cohort of 12 patients will be treated. If objective anti-tumor effects are observed, the cohort will be expanded to include a total number of 38 subjects. Grade II gliomas are also eligible but they will constitute an extra small cohort.
* To further assess the anti-tumor activity of AZD4547 for patients with recurrent glioma with FGFR-TACC fusion based on Overall Response Rate for patients with a measurable residue.
* To further assess the anti-tumor activity of AZD4547 for patients with recurrent glioma with FGFR-TACC fusion based on the duration of PFS
* To further assess the anti-tumor activity of AZD4547 for patients with recurrent glioma with a FGFR-TACC fusion based on Overall Survival AZD4547 Exploratory objectives - To elucidate the mechanism of response and resistance (primary and secondary) by exploratory biomarker analysis Experimental design: This is a phase II study in patients diagnosed with a FGFR3-TACC3 or FGFR1-TACC1 fusion positive glioma presenting with a recurrence of the disease after chemotherapy and radiotherapy. RNA will be systematically screened for the presence of FGFR-TACC in each of the 11 participating centers, and IHC for FGFR3 hyperexpression. The investigators also encourage a wide use of FGFR3 IHC in non participating centers in order to identify additional potential candidates who can be referred to one of the 11 centers for assessment of FGFR-TACC expression by RNA analysis..
Patients will receive AZD4547 at a dose of 80mg bd on a continuous schedule, until disease progression. With the following hypothesis: P0: PFS6=15%, P1: PFS6=35%, with alpha=5% and power=80%, an initial cohort of 12 patients will be treated. If objective anti-tumor effects are observed, the cohort will be expanded to include a total number of 38 subjects. Grade II gliomas are also eligible but they will constitute an extra small cohort.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2014-005428-81 | EUDRACT_NUMBER | None | View |