E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent grade III or IV glioma with FGFR3-TACC3 or FGFR1-TACC1 fusion positive by RT-PCR |
Recurrent grade III or IV glioma with FGFR3-TACC3 or FGFR1-TACC1 fusion positive by RT-PCR |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018336 |
E.1.2 | Term | Glioblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
- To characterize the safety and tolerability 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.
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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.
- To characterize the safety and tolerability 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.
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E.2.2 | Secondary objectives of the trial |
- To characterize the safety, and 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 |
- To characterize the safety, and 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
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ADN and ARN from frozen tumor samples |
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E.3 | Principal inclusion criteria |
" Recurrent grade III or IV glioma with FGFR3-TACC3 or FGFR1-TACC1 fusion positive by RT-PCR
" Recurrence occurring more than three months from the end of the radiotherapy or occurring outside the irradiated volume
" Age 18 years
" WHO 0-2 (KPS>50)
" Adequate biological parameters: blood count, renal function, liver function, calcium, phosphate
" Use of effective means of contraception (men and women) in subjects of child-bearing potential or evidence of post-menopausal status |
" Recurrent grade III or IV glioma with FGFR3-TACC3 or FGFR1-TACC1 fusion positive by RT-PCR
" Recurrence occurring more than three months from the end of the radiotherapy or occurring outside the irradiated volume
" Age 18 years
" WHO 0-2 (KPS>50)
" Adequate biological parameters: blood count, renal function, liver function, calcium, phosphate
" Use of effective means of contraception (men and women) in subjects of child-bearing potential or evidence of post-menopausal status
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E.4 | Principal exclusion criteria |
" Pregnancy or breast-feeding women
" Congestive heart failure, long QT or risk factors for long QT, important abnormalities in rhythm and heart conduction
" History of myocardial infarction, unstable angina, stroke or transient ischemic attack within the last 6 months
" Major surgical procedure (excluding placement of vascular access) within 2 weeks prior to study enrolment
" As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required
" Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD4547
" Previous history of retinal pigmented epithelial detachment RPED, previous laser treatment or intra-ocular injection for macular degeneration previous history of retinal vein occlusion (RVO) and retinal degenerative disease or any relevant other clinically relevant chorioretinal defect
" Any investigational agents or study drugs from a previous clinical study within 30 days before the first dose of study treatment
" Any chemotherapy, anticancer immunotherapy or anticancer agents within 4 weeks (6 weeks for nitrosourea) before the first dose of study treatment,
" Potent inhibitors or inducers of CYP3A4 or 2D6 or substrates of CYP3A4 within the required washout period
" Prior exposure to AZD4547 or any other anti-FGFR drug
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" Pregnancy or breast-feeding women
" Congestive heart failure, long QT or risk factors for long QT, important abnormalities in rhythm and heart conduction
" History of myocardial infarction, unstable angina, stroke or transient ischemic attack within the last 6 months
" Major surgical procedure (excluding placement of vascular access) within 2 weeks prior to study enrolment
" As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required
" Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD4547
" Previous history of retinal pigmented epithelial detachment RPED, previous laser treatment or intra-ocular injection for macular degeneration previous history of retinal vein occlusion (RVO) and retinal degenerative disease or any relevant other clinically relevant chorioretinal defect
" Any investigational agents or study drugs from a previous clinical study within 30 days before the first dose of study treatment
" Any chemotherapy, anticancer immunotherapy or anticancer agents within 4 weeks (6 weeks for nitrosourea) before the first dose of study treatment,
" Potent inhibitors or inducers of CYP3A4 or 2D6 or substrates of CYP3A4 within the required washout period
" Prior exposure to AZD4547 or any other anti-FGFR drug
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome
The 95% confidence interval of the 6-months PFS will be computed. Progression-free survival is defined as the time from inclusion to progression or death due to any cause. Subjects who have not experienced an event at 6 months will be censored.
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Primary outcome
The 95% confidence interval of the 6-months PFS will be computed. Progression-free survival is defined as the time from inclusion to progression or death due to any cause. Subjects who have not experienced an event at 6 months will be censored.
Secondary outcome
- Overall survival and progression-free survivalwill be estimated by the Kaplan-Meier method.
Overall survival will be measured from the date of inclusion to the date of death from any cause. Patients who have not died at the time of the analysis or who are lost to follow-up will be censored at the date of last contact. Progression-free survival is defined as the time from inclusion to progression or death due to any cause. Subjects who have not experienced an event at the time of data cut-off will be censored.
- An estimate of overall response rate and its 95% CI will be calculated.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary outcome
- Overall survival and progression-free survivalwill be estimated by the Kaplan-Meier method.
Overall survival will be measured from the date of inclusion to the date of death from any cause. Patients who have not died at the time of the analysis or who are lost to follow-up will be censored at the date of last contact. Progression-free survival is defined as the time from inclusion to progression or death due to any cause. Subjects who have not experienced an event at the time of data cut-off will be censored.
- An estimate of overall response rate and its 95% CI will be calculated. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |