Study Investigating the Effect of Everolimus Monotherapy in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of everolimus treatment of patients with advanced NSCLC. The rationale for investigating everolimus in advanced NSCLC previously treated with chemotherapy or chemotherapy plus EGFR inhibitors, like gefitinib or erlotinib, is based on following: The medical need for the better therapy for advanced NSCLC and limited efficacy of the currently available therapy in advanced NSCLC. Postulated association of relevant cell-signaling pathways targeted by everolimus with different aspects of oncogenesis, disease progression, and response/resistance to treatment. Effectiveness of everolimus and rapamycin in preclinical models of lung cancer Early reports of clinical responses to monotherapy with mTOR inhibitors in advanced NSCLC. There is evidence that an enhanced PI3K/Akt/mTOR pathway, which is inhibited by everolimus, may be one of the key changes accounting for different aspects of oncogenesis, disease progression, and response/resistance to NSCLC cancer treatment. The use of the mTOR inhibitor everolimus in treatment of advanced NSCLC would be a novel therapeutic approach that proposes to logically manipulate the cell's regulatory pathways to enable control of tumor growth.

Official Title
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Open Label, Non-randomized, Phase 2 Study Investigating the Effect of RAD001 Monotherapy in Patients With Advanced NSCLC Previously Treated With Either Chemotherapy Only or With Chemotherapy and EGFR Inhibitor(s)

Conditions
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Non-small-cell Lung Carcinoma

Intervention / Treatment
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* Drug: RAD001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced (unresectable or metastatic) NSCLC Tissue sample of the metastatic or primary tumor available for pathology evaluation and molecular marker analyses Patients who have received ≤ 2 chemotherapy regimens, one of which must have included cisplatinum or carboplatin, and who have documented evidence of tumor progression (Arm 1) Patients who have received ≤ 2 chemotherapy regimens, one of which must have included cisplatinum or carboplatin as well as a small molecule EGFR inhibitor (as a separate regimen) with documented tumor progression despite at least 4 weeks therapy with either gefitinib or erlotinib (Arm 2) Exclusion Criteria: Concurrent therapy with agents used otherwise as anticancer therapy (for example, methotrexate for rheumatoid arthritis) Any investigational drug, other than EGFR inhibitor (Arm 2), within the preceding 4 weeks Chronic treatment with steroids or another immunosuppressive agent Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: previously treated with chemotherapy only<br>patients previously treated with chemotherapy only (at most 2 prior regimens one of which must have been platinum-based) and no EGFRI | Drug: RAD001<br> <br> * Other names: Everolimus;|
| Experimental: previously treated with chemotherapy + small<br>patients previously treated with chemotherapy (at most 2 prior regimens one of which must have been platinum-based) and with one small molecule EGFRI | Drug: RAD001<br> <br> * Other names: Everolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy based on the evaluation of objective tumor response rate (RR) |  | until progressive disease or unacceptable toxicity. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety of RAD001 monotherapy |  | as long as patients are in the study | 
| To assess additional clinical efficacy of RAD001 |  | as long as patients are in the study | 
| To assess the steady state levels of RAD001 in blood |  | as long as patients are in the study | 
| To investigate potential molecular markers predictive of clinical effect |  | as long as patients are in the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung cancer, non-small cell, everolimus, Non-small cell lung cancer (NSCLC)