Glioma treated with AZD4547

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2014-005428-81-FR
• Date of registration: 19/01/2016
• Prospective Registration: No
• Primary sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
• Public title: Glioma treated with AZD4547
• Scientific title: A Phase I/II, Open-Label, Multicentre Study to Assess The Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of AZD4547 in Patients with glioma positive for an FGFR fusion Relapsed/Refractory -TARGET study - TARGET
• Date of first enrolment: 06/07/2015
• Target sample size: 38
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005428-81
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: open label; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Italy, United Kingdom

Contacts

• Name: DRCD Hôpital Saint Louis
• Affiliation: Assistance Publique Hôpitaux de Paris

• Name: DRCD Hôpital Saint Louis
• Affiliation: Assistance Publique Hôpitaux de Paris

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Recurrent grade III or IV glioma with FGFR3-TACC3 or FGFR1-TACC1 fusion positive by RT-PCR
MedDRA version: 18.1 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: AZD4547
Pharmaceutical Form: Coated tablet
INN or Proposed INN: AZD4547
Current Sponsor code: AZD4547
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: - 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

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.

Timepoint(s) of evaluation of this end point: 6 months

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: 6 months

Secondary ID(s)

P140402

Source(s) of Monetary Support

ASTRA ZENECA

Ethics review

Status: Approved
Approval date:
Contact: