Entry Detail
General information | |
Database: | DB00076 |
Objective: | Preclinical data demonstrates synergistic activity of combined EGFR and mTOR inhibition. they undertook a phase I trial of temsirolimus(T) and EKB569(EGFR TKI, E) to determine the safety and tolerability |
Authors: | Bryce AH, et al |
Title: | Phase I study of temsirolimus in combination with EKB569 in patients with advanced solid tumors. |
Journal: | Invest New Drugs. |
Year: | 2012 |
PMID: | 21881915 |
Trial Design | |
Clinical Trial Id: | NA |
Agent: | EKB569 |
Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
Cancer Type: | advanced solid tumors |
Cancer Subtype: | advanced solid tumors |
Therapy Type: | com |
Therapeutic Combination Type: | 1 |
Therapeutic Combination Content: | temsirolimus+EKB569 |
Study Type: | Phase I |
Key Patients Feature: | Patients over 18 years of age with histologic proof of cancer that was unresectable.Nearly all were Caucasian (41 patients, 93%), with 2 African American and 1 Asian |
Biomarker: | NA |
Biomark Analysis: | NA |
Control Group Info: | single arm |
Treatment Info: | patients were treated on a 28 day cycle.In the original dose escalation cohort (Cohort A1), EKB569 was given orally on a daily basis on days 1-28, and temsirolimus was given orally on days 1-7 and 15-21 with the dose escalations of both drugs as part of the schema. The intermittent oral dosing schedule for the temsirolimus was modeled on previousphase I data with a significant reduction of the starting dose |
Primary End Point: | MTD, PK and toxicity |
Secondary End Point: | NA |
Patients Number: | 48 |
Trial Results | |
DLT_MTD: | MDT: E, 35 mg daily and T, 30 mg on days 13 and 1517 using a 28day cycle |
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): | nausea, diarrhea, fatigue, anorexia, stomatitis, rash, anemia, neutropenia, thrombocytopenia, and hypertriglyceridemia;The most frequent grade 3/4 toxicities were diarrhea, dehydration, and nausea and vomitin |
Conclusions: | This combination of agents is associated with tolerable toxicities at doses that induced responses. PK studies revealed no interaction bettheyen the drugs. Further investigations of this targeting strategy may be attractive in renal cell carcinoma, non small cell lung cancer, alveolar sarcoma, and carcinoid tumor. |