A Phase II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation of Oral mTOR-inhibitor Everolimus (RAD001) 10 mg Daily in Patients Suffering From Classic or Endemic Kaposi's Sarcoma
A Phase II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation of Oral mTOR-inhibitor Everolimus (RAD001) 10 mg Daily in Patients Suffering From Classic or Endemic Kaposi's Sarcoma
Classic Kaposi's sarcoma (CKS) is an angioproliferation associated with human herpes virus 8 (HHV8), which sometimes requires systemic treatment. Rapamycin and everolimus are mTOR inhibitors. The PI3K-AKT-mTOR pathway is activated in CKS.The aim of this study is to evaluate the rate of clinical response and tolerance to everolimus 10mg/d in CKS. Patients suffering from CKS will be enrolled in a multicenter two-stage phase II trial. At inclusion, all patients will have at least 10 lesions or more than one limb or 3% of body surface affected, in the absence of symptomatic visceral CKS. The primary endpoint is objective response to everolimus after 6 months therapy (complete or partial response per ACTG criteria). The trial is planned using Simon's minimax two-stage design to demonstrate a response rate of 50% as compared to 20% with type I error rate 2.5% and power of 90%. Accordingly, 11 patients will to be enrolled in the first stage and provided at least 3 patients responded, 15 patients will be accrued in a second stage.
The primary endpoint is objective response to everolimus after 6 months therapy (complete or partial response per ACTG criteria).
Secondary endpoints are response according to physician global assessment, lesions size , lesions infiltration, lymphedema, tolerance, pharmacodynamic (pathologic, angiogenic and lymphangiogenic biomarkers, HHV8 viral load sequential evaluation in the lesions, pharmacokinetic evaluation.
Inclusion Criteria:
Histologic confirmed classic or endemic KS (non transplant non HIV patients) > 18 Years old at least 10 lesions or more than one limb or 3% of body surface affected, in the absence of symptomatic visceral KS Presence of at least 4 targets lesions > 5mm At least 4 weeks wash out from any KS specific therapy ECOG < 2
Exclusion Criteria:
immunosupressive regimen patients HIV positive creatinine clearance <40ml/mn,AST ALT>3N, neutropénia<1500, thrombopenia<150000, anemia<8g/dL