CMTTdb

An integrated database for cancer molecular targeted thearpies

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.