Temsirolimus and Irinotecan for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations (TIRASMUS)
The purpose of this study is to investigate the safety and efficacy of temsirolimus as a single drug, and of temsirolimus in combination with irinotecan in chemotherapy resistant patients with KRAS mutated colorectal cancer.
Metastatic Colorectal Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||Phase II Study of Temsirolimus and Irinotecan in Chemotherapy Refractory Patients With KRAS Mutated Metastatic Colorectal Cancer|
- Objective response rates
- Progression free survival
- Overall survival
- Translational Research
|Study Start Date:||March 2009|
|Study Completion Date:||June 2011|
|Primary Completion Date:||January 2011 (Final data collection date for primary outcome measure)|
Active Comparator: Response or stable disease
will receive Temsirolimus
Will receive a combination of Temsirolimus and Irinotecan
|Drug: Irinotecan Drug: Temsirolimus|
Chemotherapy resistance is a major challenge in metastatic colorectal cancer (mCRC), and EGFR inhibitors have been introduced as 3rd line treatment to chemotherapy refractory patients. However, it has recently been established that response to treatment with irinotecan and cetuximab is confined to patients with wtKRAS tumors. Therefore, downstream targets are being proposed as potential inhibitors of the EGFR signalling in tumours with KRAS mutations. mTOR is a central intracellular signalling molecule and a rational approach for potential reversion of chemotherapy resistance in these patients.
Preclinical data suggest that different solid tumors could respond to mTOR inhibitors and report on enhanced antitumor activity in combination with different traditional cytostatic drugs. Furthermore recent preclinical data suggest that mTOR inhibition may induce tumor reduction in colon cancer xenographs. Temsirolimus (CCI-779) has been widely investigated in different clinical settings and is presently registered for treatment of renal cell carcinomas. Furthermore, is has recently shown response in metastatic breast cancer patients, but at present there are no clinical data on efficacy or safety in metastatic colorectal cancer patients.
The present study aims at investigating the safety and efficacy of monotherapy temsirolimus and a combination of temsirolimus and irinotecan in chemotherapy resistant, KRAS mutated colorectal adenocarcinomas.
|Rigshospitalet, Department of Oncology|
|Copenhagen, Denmark, DK-2100|
|Vejle Hospital, Dept. of Oncology|
|Study Chair:||Anders Jakobsen, MD, DMSc||Vejle Hospital|
|Principal Investigator:||Karen-Lise G Spindler, MD, PhD||Vejle Hospital|