Trial Information

A Phase I Study of the mTOR Inhibitor Temsirolimus Plus Capecitabine in Patients With Advanced Malignancies

This is a Phase I study designed to assess the safety and clinical activity of temsirolimus
in combination with capecitabine in patients with advanced malignancies. Because the
toxicities of capecitabine are well established, and based on a previous clinical trial of
temsirolimus and continuous infusion 5-fluorouracil, an alternating dose escalation plan
will be employed.

The first stage of the study will be performed to identify the maximally tolerated dose of
the combination, when capecitabine is given on a every 2 week schedule. The starting dose of
temsirolimus will be 15-mg IV on day 1 and 8 plus capecitabine 1000 mg/m2 by mouth twice a
day on days 1-7 of a 14 day schedule. Patients will be enrolled in a standard 3+3 dose
escalating fashion to a maximum dose of temsirolimus of 25-mg and a maximum dose of
capecitabine of 1750 mg/m2 twice a day.

If the maximally tolerated dose is determined for the every 2 week schedule, then in the
second stage of the study a similar dose escalation plan will be employed for an every 3
week schedule.