Phase I/II study of S 49076, a multi-target inhibitor of c-MET, AXL, FGFR in combination with bevacizumab in patients with recurrent glioblastoma multiforme
| ISRCTN | ISRCTN11619481 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11619481 |
| EudraCT/CTIS number | 2013-003079-37 |
| Secondary identifying numbers | CL1-49076-002 |
- Submission date
- 05/12/2014
- Registration date
- 13/02/2015
- Last edited
- 23/03/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Not provided at time of registration and not expected to be available in the future
Contact information
Mrs Valérie Fautrier
Public
Public
50 rue Carnot
Suresnes
92284
France
Study information
| Study design | International multicenter open-label dose-finding and non-comparative efficacy study with one-way cross-over |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Dose-finding study followed by a randomised efficacy study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Phase I/II study of S 49076, a multi-target inhibitor of c-MET, AXL, FGFR in combination with bevacizumab in patients with recurrent glioblastoma multiforme |
| Study acronym | N/A |
| Study hypothesis | To evaluate the safety and efficacy of S 49076 in combination with bevacizumab in patients with recurrent glioblastoma multiforme (GBM). This is a phase I, dose-finding study of S 49076 in combination with bevacizumab followed by a randomised efficacy phase II study. |
| Ethics approval(s) | Ethics approval was obtained before recruitment of the first participants |
| Condition | Glioblastoma multiforme |
| Intervention | Capsules containing 100 mg of S 49076 (oral use). The dose will be gradually escalated, following an algorithm-based 3+3 design, from level 1 at 400 mg/day to the MTD, with the possibility to de-escalate. A panel of four doses of S49076 (300, 400, 500 and 600 mg) could be tested. Solution for infusion of bevacizumab; each ml of concentrate contains 25 mg of bevacizumab. Bevacizumab will be administered on day 1 and 15 of each cycle, 28-days/cycle. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | S49076 |
| Primary outcome measure | Phase I: 1. Dose Limiting Toxicity and recommended phase II dose in combination of bevacisumab, at end of phase I part 2. Safety profile: 2.1. Adverse Events at each visit 2.2. Coagulation: within 7 days prior to the first test drug administration, D1 of each cycle and Withdrawal Visit (WV) 2.3. Physical and clinical neurological examination, vital signs, haematology, biochemistry and urinalysis: within 7 days prior to the first test drug administration, D1 and D15 of each cycle and WV 2.4. ECG parameters: within 7 days prior to the first test drug administration, D1, D2 and D15 of cycle 1, after D1 and D15 of each cycle and WV 2.5. LVEF assessment: at inclusion, on D28 every 2 cycles from cycle 1 and WV Phase II: 1. Progression-free survival rate according to RANO (Response Assessment in Neuro-Oncology) criteria: at 6 months (PFS-6) |
| Secondary outcome measures | Phase I: 1. Pharmacokinetic evaluation at D1, D2, D15 and D28 of cycle 1 and D1 of cycle 2 2. Pharmacodynamic evaluation at D1 of each cycle 3. Tumour response evaluation at within 14 days prior to the first test drug administration, D28 at each cycle and WV Phase II: 1. ORR, CBR, OS, progression-free survival, response duration, duration of clinical benefit: within 14 days prior to the first test drug administration, D28 at each cycle and WV 2. Safety tolerance profile of the combination: 2.1. AE: at each visit 2.2. Physical and clinical neurological examinations, vital signs, ECG, Haematology, Biochemistry and Urinalysis: within 7 days prior to the first test drug administration, D1 and D15 of each visit and WV 2.3. Activity profile in subgroup with c-Met amplification or mutation: within 14 days prior to the first test drug administration, D28 at each cycle and WV 2.4. Quality of life: within 14 days prior to the first test drug administration, D28 at each cycle and WV |
| Overall study start date | 10/03/2014 |
| Overall study end date | 03/11/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 115 |
| Participant inclusion criteria | 1. Male or female patient aged > or = 18 years old 2. Histologically confirmed diagnosis of glioblastoma multiforme (WHO grade IV). Patients will be eligible if original histology was low-grade glioma and a subsequent diagnosis of glioblastoma was made 3. Unequivocal evidence of first progression/recurrence after standard treatment with combined chemo-irradiation (including a possible combination of temozolomide with an investigational agent) performed by MRI within 2 weeks before the first test drug administration 4. No more than one prior line of treatment 5. Patients must have measurable tumour disease as defined by RANO 6. Ability to swallow oral capsules |
| Participant exclusion criteria | 1. Pregnant or breastfeeding women 2. Involvement in another therapeutic interventional trial at the same time or within 3 weeks prior to the first day of test drug administration 3. Major surgery (including craniotomy) within 4 weeks prior to the first day of test drug administration or minor surgical procedures (e.g., core biopsy or fine needle aspiration) within 14 days 4. Chemotherapy within 4 weeks (6 weeks for nitroso-ureas) prior to the first day of test drug administration 5. Radiotherapy within 3 months prior to the diagnosis of progression 6. Prior treatment with bevacizumab or other VEGF-receptor targeted agent 7. Prior treatment with a PI3K inhibitor, HGF or Met pathways for phase II part 8. Prior treatment with carmustine wafer 9. Impaired cardiac function |
| Recruitment start date | 03/10/2014 |
| Recruitment end date | 04/06/2016 |
Locations
Countries of recruitment
- France
- Switzerland
Study participating centres
AP-HP Pitié-Salpêtrière
47-83 Boulevard de l'Hôpital
Paris
75013
France
Paris
75013
France
University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois)
Rue du Bugnon 46
Lausanne
1011
Switzerland
Lausanne
1011
Switzerland
Sponsor information
Institut de Recherches Internationales Servier (France)
Industry
Industry
50 rue Carnot
Suresnes
92284
France
| Website | http://www.servier.com/ |
|---|---|
"ROR" |
https://ror.org/034e7c066 |
Funders
Funder type
Industry
ADIR
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Summary results and lay summary are published on www.clinicaltrials.servier.com. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from www.clinicaltrials.servier.com if a Marketing Authorisation has been granted after 1st January 2014. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| Basic results | No | No |
Editorial Notes
23/03/2018: A link to the basic results was added and the publication and dissemination plan was updated.
06/04/2017: The overall trial end date was changed from 30/06/2017 to 03/11/2016.
09/08/2016: The recruitment end date was changed from 13/11/2016 to 04/06/2016.
