Phase I Study of the Combination of Axitinib (AX) Plus Everolimus (EV) in Patients With Malignant Advanced Solid Tumors
Phase I study of the combination of axitinib (AX) plus everolimus (EV) in patients with
malignant advanced solid tumors.
- To determine the recommended dose for phase II study of the combination of AX + EV
- To determine the safety profile and predictive factors for toxicity, pharmacokinetics
(PK), and efficacy in adult solid tumors.
- To assess functional vascular imaging (FVI) as surrogate marker of activity, biomarkers
predictive of activity and preliminary efficacy data in metastatic RCC, untreated with
Phase I, multicentre, open-label, non-randomized, sequential algorithm based dose-finding
(3+3), clinical study in successive cohorts of patients.
Patients will take both drugs orally, every day, without planned rest period (AX bid and EV
once a day). By convention one cycle is 28 days. At the first cycle patients will take one
week of AX single agent before starting EV. Patients will be treated at increasing dose
levels (DLs) in successive cohorts of 3-6 patients according to the number of patients with
dose limiting toxicities (DLT) until the maximum tolerated dose (MTD; i.e. the DL at which
<= 1/6 patient experiences a DLT during the first cycle). All decision concerning
qualification for DLT, dose escalation, study termination, inclusion of additional patients,
will be taken by a Trial Monitoring Committee..
The MTD will not be higher than the recommended dose of each single agent. Six additional
patients will be entered at the MTD to confirm the feasibility of the dose and preliminarily
assess the efficacy of the combination in patients with RCC untreated with antiangiogenics.
Three levels of dose will be explored.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients with DLT (dose limiting toxicity) during the first cycle (first 28 days of the combination of both study compounds), per dose level explored
A DLT will be one of the following adverse events, with a possible relationship to the study medications Febrile, related bleeding or any grade 4 neutropenia or thrombocytopenia, grade 3 non-hematological toxicity, unless adequately treated with usual symptomatic therapy grade 4 non-hematological toxicity study treatment interruption > 2 weeks, inability to deliver at least 80% of the intended doses of axitinib and/or everolimus between day 8 and 35 due to toxicity.
during cycle 1
University Hospital, Bordeaux
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)