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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Everolimus everolimus 10 mg per day |
Drug: everolimus
everolimus per os 10mg per day
|
Outcome Measures
Primary Outcome Measures
- objective response to everolimus after 6 months therapy [duration of study 30 months]
objective response to everolimus after 6 months therapy (complete or partial response per ACTG criteria).
Secondary Outcome Measures
- response according to physician global assessment, lesions size , lesions infiltration [30 months]
response according to physician global assessment, lesions size , lesions infiltration
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Saint Louis | Paris | France | 75010 |
Sponsors and Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
Investigators
- Study Director: Celeste Lebbé, MD, PhD, Institut National de la Santé Et de la Recherche Médicale, France
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- C06-46