Glioblastoma multiforme Cancer
Conditions
Interventions
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-escal
each ml of concentrate contains 25 mg of bevacizumab. Bevacizumab will be administered on day 1 and 15 of each cycle, 28-days/cycle.
Sponsors
Institut de Recherches Internationales Servier (France)
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
France, Switzerland
Contacts
Public ContactValérie Fautrier
Outcome results
None listed