Clinical trial NCT00654420
Conditions: Carcinoma, Non-small-cell Lung
Sponsor: Merck Sharp & Dohme LLC
Start date: 2008-03-19; Completion date: 2012-02-13
Enrollment: 95 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase I/IIa study to evaluate safety and efficacy of dalotuzumab (MK-0646) in combination with erlotinib in participants with recurrent Non-Small Cell Lung Cancer (NSCLC). The Phase I part of this study will determine the highest tolerated dose of dalotuzumab to be given in combination with erlotinib. The primary hypothesis for the Phase I part of the study is that administration of erlotinib in combination with dalotuzumab in participants with recurrent NSCLC is generally well-tolerated as evidenced by accumulated safety data from this trial. The Phase II part of this study will investigate how well dalotuzumab works in conjunction with erlotinib at treating recurrent NSCLC. The primary hypothesis for the Phase II part of this study is that administration of erlotinib in combination with dalotuzumab in participants with recurrent NSCLC results in improvement in Progression Free Survival (PFS) compared to participants treated with erlotinib alone. PFS is defined as the time from randomization until either the emergence of radiographic evidence of disease progression (as documented by an independent core laboratory) or death due to any cause, whichever occurs first.

Detailed description:
Dalotuzumab is a humanized monoclonal antibody (mAb) that targets the Insulin-like Growth Factor Receptor (IGF-1R). Dalotuzumab may act through:

* Inhibition of IGF-1-mediated cell signaling to cause reductions in tumor growth and spread
* Antibody dependent cell-mediated cytotoxicity

In preclinical studies, dalotuzumab improved the activity of an anti-Epidermal Growth Factor Receptor (EGFR) mAb and the activity of Erlotinib, a small molecule inhibitor of EGFR

Trial Duration of Treatment: Participants will continue on the study for as long as their disease is not progressing and they do not have unmanageable side effects from the treatment.

Arms: arm 1: During the Phase I part of the study, participants receive dalotuzumab intravenously (IV) at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who do not have disease progression and are satisfactorily tolerating study drug can continue to receive study drug. arm 2: During the Phase I part of the study, participants receive dalotuzumab intravenously (IV) at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who do not have disease progression and are satisfactorily tolerating study drug can continue to receive study drug. arm 3: During the Phase II part of the study, participants are randomized to receive dalotuzumab intravenously (IV) at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects. arm 4: During the Phase II part of the study, participants are randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Interventions: intervention 1: Dalotuzumab intervention 2: Erlotinib
Intervention descriptions: intervention 1: Dalotuzumab 20 mg/mL in sterile solution. Intravenous (IV) infusion over 60 minutes at 5 mg/kg, administered weekly at dosage according to treatment group. intervention 2: Open-label erlotinib administrated orally (tablets) by mouth (PO) at 150 mg daily.

Protocol documents: