| General information |
| Database: | DB00888 |
| Objective: | To establish the safety, tolerability, and pharmacokinetic parameters of CCI779, a selective inhibitor of the mammalian target of rapamycin, in patients with advanced cancer. |
| Authors: | Raymond E, et al |
| Title: | Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI779, a novel mTOR inhibitor, in patients with cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2004 |
| PMID: | 15136596 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | temsirolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I pharmacokinetic study |
| Key Patients Feature: | histologically confirmed diagnosis of solid tumor refractory to standard therapy or for whom no standard therapy existed; age more than and equal to 18 years; life expectancy more than and equal to 3 months; |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | CCI779 given as a weekly 30 minutes intravenous (I.V.) infusion. |
| Primary End Point: | safety, tolerability, and pharmacokinetic parameters |
| Secondary End Point: | NA |
| Patients Number: | 24 |
| Trial Results |
| DLT_MTD: | DLT was defined as more than and equal to grade 3 nonhematological toxicity (excluding alopecia, untreated nausea and vomiting, and/or serum triglycerides if < 1, 500 mg/dL and recovered within 1 week), grade 4 thrombocytopenia, grade 4 neutropenia lasting > 5 days, grade 4 febrile neutropenia requiring hospitalization, or treatment delay of > 2 weeks as a result of unresolved toxicity.The MTD was defined as the dose level at which more than and equal to 33% of the patients would experience doselimiting toxicity (DLT). |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent drugrelated adverse events were dermatologic toxicities and mucositis/stomatitis (18 of 24 patients; |
| Conclusions: | CCI779 displayed no immunosuppressive effects with manageable and reversible adverse events at doses up to 220 mg/m(2), the highest dose tested. Based on our results, weekly doses of 25, 75, and 250 mg CCI779 not based on classical definitions of maximumtolerated dose are being tested inphase II trials in patients with breast and renal cancer. |