Condition category
Cancer
Date applied
05/12/2014
Date assigned
13/02/2015
Last edited
09/08/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration and not expected to be available in the future

Trial website

Contact information

Type

Public

Primary contact

Mrs Valérie Fautrier

ORCID ID

Contact details

50 rue Carnot
suresnes
92284
France

Additional identifiers

EudraCT number

2013-003079-37

ClinicalTrials.gov number

Protocol/serial number

CL1-49076-002

Study information

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

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

Ethics approval was obtained before recruitment of the first participants

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

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Phase

Phase I/II

Drug names

S49076

Primary outcome measures

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 trial start date

10/03/2014

Overall trial end date

30/06/2017

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

115

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

Trial participating centre

AP-HP Pitié-Salpêtrière
47-83 Boulevard de l'Hôpital
Paris
75013
France

Trial participating centre

University Hospital of Lausanne (Centre Hospitalier Universitaire Vaudois)
Rue du Bugnon 46
Lausanne
1011
Switzerland

Sponsor information

Organisation

Institut de Recherches Internationales Servier (France)

Sponsor details

50 rue Carnot
Suresnes
92284
France

Sponsor type

Industry

Website

http://www.servier.com/

Funders

Funder type

Industry

Funder name

ADIR

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We will comply with regulatory requirement

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

09/08/2016: the recruitment end date was changed from 13/11/2016 to 04/06/2016.