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
Overview
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Institut National de la Santé Et de la Recherche Médicale, France
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- objective response to everolimus after 6 months therapy
Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Everolimus
everolimus 10 mg per day
Intervention: everolimus (Drug)
Outcomes
Primary Outcomes
objective response to everolimus after 6 months therapy
Time Frame: duration of study 30 months
objective response to everolimus after 6 months therapy (complete or partial response per ACTG criteria).
Secondary Outcomes
- response according to physician global assessment, lesions size , lesions infiltration(30 months)