Investigation of gemcitabine combined with temsirolimus, in patients with inoperable or metastatic pancreatic cancer. A phase I-II study by the Hellenic Cooperative Oncology Group with biomarker evaluation (HE3/07)

Phase I: In the phase I, 2-30 patients will be accrued. A minimum of 2 patients will be treated at the first dose levels. As per protocol design there is no -1 level and therefore, if two DLTs occur at the first two patients, trial has to be closed prematurely. Each dose level will include at least 3 subjects. Patients will receive treatment consisting of temsirolimus [up to 25 milligrams (mg) weekly] followed by infusion of gemcitabine. The starting doses of temsirolimus and gemcitabine will be 15mg [30 min intravenous (iv) infusion] and 800 mg/m2 [30 min intravenous (iv) infusion] respectively. Three subjects will be included in each dose level. If no subject experiences Dose Limiting Toxicity (DLT), the study moves to the higher dose level. Level 1 Gemcitabine: 800mg/m2 Days 1, 15 four week cycle, Temsirolimus 15 mg Weekly Level 2 Gemcitabine: 800mg/m2 Days 1, 15 four week cycle, Temsirolimus: 20mg Weekly Level 3 Gemcitabine: 800mg/m2 Days 1, 15 four week cycle, Temsirolimus 25mg Weekly Level 4 Gemcitabine: 1000mg/ m2 Days 1, 15 four week cycle, Temsirolimus: 20mg Weekly Level 5 Gemcitabine: 1000mg/ m2 Days 1, 15 four week cycle, Temsirolimus: 25mg Weekly If only 1 of the 3 subjects experiences DLT or other unacceptable toxicity, the number of subjects in the cohort will be increased to 6. If 2 or more of the 6 subjects experience DLT, no further dose escalation (level increase) will take place. This will be considered the Maximum Tolerated Dose (MTD) of the combination. Once the MTD is achieved and is/or exceeds the 20mg/800mg/m2 dose level, the 3 (or 6) subjects enrolled at this dose level can continue on the clinical study Phase II: All patients will start therapy with the determined proposed dose (previous dose level of the MTD) of temsirolimus and gemcitabine. Both drugs are administered on Days 1 and 15 of each 4 week cycle. Temsirolimus is also administered alone on day 8 and day 22. Treatment will be administered for 7 cycles.