A Translational, Pharmacodynamic and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer

This phase IB clinical trial studied the pharmacodynamic changes induced by everolimus in patients with previously untreated, resectable non small cell lung cancer. Using a combination of in vivo and ex vivo assessments with FDG PET, immunohistochemistry and genomic assays, evidence of mTOR pathway perturbation was assessed in patients treated with everolimus, an allosteric mTOR inhibitor. Untreated patients served as controls for comparison. Key results from this work include a dose-dependent biologic effect of everolimus, signal of activity in RAS mutant tumors as well as near complete metabolic and pathologic response in a case of sarcomatoid lung cancer. These findings represent novel translational insights that can guide future development of mTOR inhibitors in lung cancer and other tumor types. Additionally, metabolic response and anatomic tumor shrinkage observed in a significant proportion of patients following a short of duration of therapy with everolimus suggests potential clinical utility of this agent in carefully-selected lung cancer patients.]]>
Inclusion Criteria: Patients were eligible if newly diagnosed with non-small cell lung cancer (NSCLC) of all histologies and deemed to be surgically resectable Stage I-IIIA disease. Other eligibility requirements included age ≥ 18 years, ECOG performance status of 0-2, adequate bone marrow function (WBC ≥3,000 cells/mm3, ANC ≥1,500 cell/mm3, platelets ≥100,000 cells/mm3), renal function (creatinine <1.5 X ULN), hepatic function (bilirubin ≤1.5 X ULN, SGOT/SGPT ≤2.5 X ULN, alkaline phosphatase ≤5 X ULN). Exclusion Criteria: Specific exclusion factors included inability to swallow pills, known hypersensitivity to everolimus or any of its excipients; pregnancy or breast-feeding; major intercurrent medical, psychiatric or social impairment that would limit compliance with study requirements and chronic treatment with systemic steroids or other immunosuppressive agent.]]>
The study was activated in 2007First patient was enrolled on 3/21/2007Last patient was enrolled on 2/22/2013There is currently no patient on active treatment]]>