| General information |
| Database: | DB00796 |
| Objective: | Everolimus is a novel inhibitor of the mammalian target of rapamycin pathway, which is aberrantly activated in nonsmall cell lung cancer (non small cell lung cancer). The authors conducted a phase 1 and pharmacokinetic study of everolimus and docetaxel for recurrent non small cell lung cancer. |
| Authors: | Ramalingam SS, et al |
| Title: | Phase 1 and pharmacokinetic study of everolimus, a mammalian target of rapamycin inhibitor, in combination with docetaxel for recurrent/refractory nonsmall cell lung cancer. |
| Journal: | Cancer. |
| Year: | 2010 |
| PMID: | 20564143 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I and pharmacokinetic study |
| Key Patients Feature: | Patients with advanced stage non small cell lung cancer and progression after prior platinumbased chemotherapy were eligible. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Sequential cohorts were treated with escalating doses of docetaxel (Day 1) and everolimus (orally daily, Days 119) every 3 weeks. Pharmacokinetic sampling of everolimus and docetaxel was done in Cycle 1. |
| Primary End Point: | determination of the recommendedphase 2 doses of the combination. |
| Secondary End Point: | NA |
| Patients Number: | 24 |
| Trial Results |
| DLT_MTD: | DLT was defined as the occurrence of one or more of the following events during cycle 1 of therapy: grade 3/4 neutropenia associated with fever; grade 4 neutropenia lasting > 7 days; grade 4 thrombocytopenia; grade more than and equal to 3 nonhematological toxicity; or a toxicityrelated delay of > 2 weeks to initiate cycle 2. An 'up and down¡¯ dose escalation scheme, with cohorts of 3 patients, was utilized. The first cohort was treated at dose level 1. If 1 of the 3 patients in a cohort experienced DLT, 3 more patients were added at the same level. If 0 of 3 initial patients or 1 of 6 patients in an expanded cohort experienced DLT, the dose for the next cohort was escalated by one level. Escalation stopped, and deescalation by 1 dose level began as soon as 2 patients at a dose level experienced DLT. If only 3 patients had been treated at the previous dose level, up to 3 additional patients were to be entered at that dose level. Dose deescalation continued until less than and equal to 1/6 patients at a dose level experienced DLT, and that level was defined as the recommendedphase II dose.The doselimiting toxicities (DLTs) were fever with grade 3/4 neutropenia, grade 3 fatigue, and grade 3 mucositis. |
| 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): | NA |
| Conclusions: | The recommended phase 2 doses of docetaxel and everolimus for combination therapy are 60 mg/m2 and 5 mg orally daily, respectively. Promising anticancer activity has been noted. |