Clinical trial NCT00998166
Conditions: Non-Small Cell Lung Cancer
Keywords: NSCLC
Sponsor: Columbia University
Start date: 2009-06-01; Completion date: 2011-10-01
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
In the past, patients with advanced lung cancer who were inoperable underwent chemotherapy with one or more chemotherapeutic agents. More recently, novel new agents targeting specific enzymes or pathways responsible for cell division have been developed and clinicians have begun to utilize various combinations of these drugs with standard chemotherapeutic agents for the treatment of NSCLC. Some of these approaches have demonstrated a small but significant increase in survival among patients with advanced disease. Because a recently completed Phase 3 study of bevacizumab + Taxol/Carboplatin in first line NSCLC therapy demonstrated a 23% improvement in median survival, it would be appealing to see if a regimen of bevacizumab/ cisplatin/Alimta would also demonstrate a similar, or perhaps better, response rate.

Detailed description:
The majority of patients with NSCLC present with inoperable locally advanced or metastatic disease for which no curative therapy is available. For these patients, platinum based doublet combination regimens have become standard of care due to increased survival rates over platinum therapy alone.

In order to try to improve on the overall survival, clinicians have attempted to add a third cytotoxic agent to their standard regimen(s). Although this approach demonstrated an improved objective response, no additional benefit was noted in overall survival.

Recent development and approval of new targeted chemotherapies during the past 10 years has prompted clinical trials to test the efficacy of newly FDA approved agents such as gefitinib, erlotinib, and bevacizumab in advanced NSCLC.

Although gefitinib and erlotinib have both demonstrated clinical activity in refractory NSCLC, neither agent improved clinical outcome when added to standard 1st line platinum based chemotherapy. In contrast, a recently completed randomized Phase 3 trial investigating the addition of bevacizumab to 1st line paclitaxel plus carboplatin chemotherapy reported a 23% improvement in the median overall survival for the paclitaxel/carboplatin plus bevacizumab treatment arm (12.5m vs. 10.2m; p=0.007). It is therefore appealing to study a cisplatin combination with bevacizumab to determine if there is any additive benefit. Pemetrexed is an ideal agent to use in combination with cisplatin since it is well tolerated and efficacy is comparable to other cisplatin combinations. Patients will receive a maximum of 6 cycles. Those who complete 1 cycle will be evaluated for toxicity; more than 1 cycle, response.

Arms: arm 1: Chemotherapy infusion on Day 1 of a 3-week cycle
Interventions: intervention 1: Pemetrexed intervention 2: Cisplatin intervention 3: Bevacizumab
Intervention descriptions: intervention 1: 1. Pre-hydration for 1-1/2 hours at 250 ml/hour
2. Pemetrexed 500 mg/m2 IV over 10 minutes
3. Return to hydration for 30 minutes at 250 ml/hour intervention 2: 4\. Cisplatin 75mg/m2 IV over 60-120 minutes intervention 3: 5\. Bevacizumab 15mg/kg IV over 90 minutes

Protocol documents: