| General information |
| Database: | DB00075 |
| Objective: | Preclinical studies have demonstrated that the inhibition of the PI3K/Akt/mTOR pathway restores gefitinib sensitivity in resistant cancer cell lines. a phase 1 study was conducted of the combination of everolimus, an mTOR inhibitor, and gefitinib to determine a daily dose of everolimus with gefitinib in patients with advanced non small cell lung cancer (non small cell lung cancer). |
| Authors: | Milton DT, et al |
| Title: | Phase 1 trial of everolimus and gefitinib in patients with advanced non small cell lung cancer. |
| Journal: | cancer |
| Year: | 2007 |
| PMID: | 17577220 |
| 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: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | everolimus+ gefitinib |
| Study Type: | Phase I |
| Key Patients Feature: | progressive disease despite prior treatment with at least 1 chemotherapy regimen |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | hypothesis is that concurrent signal transduction inhibition within this pathway with gefitinib and everolimus would result in additive or synergistic antitumor activity in patients with advanced non small cell lung cancer |
| Treatment Info: | Oral everolimus and gefitinib were both administered daily to patients with progressive non small cell lung cancer. patients were enrolled in 3patient cohorts at everolimus dose levels of 5 and 10 mg daily. All patients received gefitinib 250 mg daily. |
| Primary End Point: | MDT, DLT and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 10 |
| Trial Results |
| DLT_MTD: | 5 mg when administered daily with gefitinib 250 mg. |
| 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: | For further study, everolimus at a dose of 5 mg daily in combination with daily gefitinib 250 mg is recommended. The 2 radiographic responses identified are encouraging. Aphase 2 trial in patients with non small cell lung cancer is under way. |