Study of Temsirolimus, Erlotinib and Cisplatin in Solid Tumors

Triple Negative Breast Cancer Clinical Trial

Official title: Phase I Study of Combined Temsirolimus, Erlotinib and Cisplatin in Advanced Solid Tumors

Status Completed

Clinical Trial Summary

This is a Phase I research study designed to determine the maximum tolerated dose (MTD) of cisplatin, temsirolimus, and erlotinib in combination for treatment in triple negative breast cancer (TNBC) patients.

Clinical Trial Description

The stratification of breast cancer patients for treatment targeting either the estrogen receptor (ER) or human epidermal growth factor receptor 2 (HER2) receptor based upon the measurement of ER/progesterone receptor (PR) and HER2 in tumor tissue has changed the treatment of breast cancer. However, the success of this stratification has resulted in the recognition that no effective rational treatment exists for patients that lack these receptors. The term "triple negative breast cancer" (TNBC) has been used to define a class of unresponsive patients, which is based upon their lack of the hormone receptors for estrogen and progesterone and the HER2 oncogene. TNBC represents a form of breast cancer for which no targeted therapy is known.

Thus, identifying and understanding the signaling pathways and receptors that contribute to triple negative tumor growth is of high priority in order to develop therapies analogous to the ones that have already been developed for HER2 and ER.

Available data from Phase I trials have demonstrated that mTOR inhibitors and EGFR inhibitors have been safely given together at doses shown to inhibit their respective targets and Phase II studies are ongoing in advanced renal cell, pancreatic, glioma, and breast (not specifically TNBC) cancers.

The rationale for adding cisplatin to erlotinib and an mTOR inhibitor are many. Cisplatin is a known active cytotoxic against breast cancer. It has non overlapping toxicity with erlotinib and TORC1 mTOR inhibitors and patients are unlikely to have been previously treated with cisplatin. Therefore, as a cytotoxic DNA damaging agent, cisplatin could trigger cell death in a cell whose survival pathways are effectively inhibited by mTOR inhibition and erlotinib. ;

Related Conditions & MeSH terms

• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

• NCT number: NCT00998036
• Study type: Interventional
• Source: Columbia University
• Status: Completed
• Phase: Phase 1
• Start date: September 2009
• Completion date: October 2012