Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Temsirolimus and pemetrexed for recurrent or refractory NSCLC
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 12
Healthy volunteers: no

Brief summary:
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination of temsirolimus and pemetrexed, as well as the response rate. The starting dose (Dose Level 1) and schedule of pemetrexed will be 500 mg/m\^2 given every 3 weeks and the starting dose (Dose Level 1) for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level.

Detailed description:
* To determine the maximum tolerated dose (MTD) of temsirolimus that could be administered weekly in combination with pemetrexed.
* To determine the dose-limiting toxicity (DLT) of temsirolimus and pemetrexed as well as other toxicities of this combination therapy.
* To describe the response rate of the combination in patients with relapsed/refractory non-small cell lung cancer (NSCLC).
* To describe phospho-Akt and phospho-S6 levels in circulating mononuclear cells before and after treatment.
* To determine the response rates in patients with NSCLC when treated with temsirolimus and pemetrexed.
* To evaluate progression-free survival in patients with NSCLC when treated with temsirolimus and pemetrexed.
* To determine the one-year survival rates in patients with NSCLC when treated with temsirolimus and pemetrexed.
* To describe phospho-Akt and phospho-S6 levels in circulating mononuclear cells before and after treatment.

Arms:
arm 1: -Dose Level 1

* Pemetrexed 500mg/m\^2 intravenous (IV) on Day 1 of each 21 day cycle
* Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle arm 2: * Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle
* Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle arm 3: * Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study.
* Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle
* Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle

Interventions: intervention 1: Pemetrexed intervention 2: Temsirolimus
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document: