| General information |
| Database: | DB00575 |
| Objective: | Ridaforolimus is an inhibitor of mammalian target of rapamycin, an integral component of the phosphatidyl 3kinase/AKT signaling pathway, with early evidence of activity in sarcomas. This multicenter, openlabel, singlearm, phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas. |
| Authors: | Chawla SP, et al |
| Title: | Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas. |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22067397 |
| Trial Design |
| Clinical Trial Id: | NCT00112372 |
| Agent: | ridaforolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | soft tissue sarcomas |
| Cancer Subtype: | soft tissue or bone sarcoma (excluding GIST) |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multicenter, openlabel, singlearm, fixeddose, phase II study |
| Key Patients Feature: | Patients 15 years of age with diagnoses of metastatic or unresectablesoft tissue or bone sarcoma (excluding GIST) and at least one measurabletumor were eligible. Four independent cohorts of patients were planned:primary bone sarcomas, leiomyosarcomas, liposarcomas, and other soft tissuesarcomas. Patients were required to have an Eastern Cooperative OncologyGroup (ECOG) performance status 1, minimum life expectancy of 3months, adequate renal and hepatic function, adequate bone marrow function(absolute neutrophil count 1.5 109/L and platelet count 100 109/L), serum cholesterol less than 350 mg/dL, and serum triglyceride less than 400mg/dL and to provide written informed consent. |
| Biomarker: | Upstream of mTOR: PTEN, pAKT, FKBP12, IGF1R;Downstream of mTOR: pS6, 4EBP1, Eif4e, p27kip1. |
| Biomark Analysis: | Archival tumor protein markers analyzed were not correlated with CBR. |
| Control Group Info: | single arm |
| Treatment Info: | pts received ridaforolimus 12.5 mg administered as a 30minute intravenous infusion once daily for 5 days every 2 weeks. |
| Primary End Point: | clinical benefit response (CBR) rate (complete response or partial response [PR] or stable disease more than and equal to 16 weeks) |
| Secondary End Point: | Safety, progression free survival (PFS), overall survival (OS), time to progression, and duration of response |
| Patients Number: | 212 |
| Trial Results |
| DLT_MTD: | Related adverse events were generally mild or moderate andconsisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue. |
| Objective Response Rate: | response rate was1.9%, with four patients achieving confirmed PR (two with osteosarcoma, one with spindle cellsarcoma, and one with malignant fibrous histiocytoma). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 15.3 weeks |
| Median OS A vs. C: | 40 weeks. |
| Adverse Event(agent arm): | Related adverse events were generally mild or moderate and consisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue. |
| Conclusions: | Singleagent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics. Aphase III trial based on these data will further define ridaforolimus activity in sarcomas. |