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

Phase 2
Completed
Conditions
Non-small-cell Lung Carcinoma
Interventions
Registration Number
NCT00124280
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
85
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
previously treated with chemotherapy onlyRAD001patients previously treated with chemotherapy only (at most 2 prior regimens one of which must have been platinum-based) and no EGFRI
previously treated with chemotherapy + smallRAD001patients previously treated with chemotherapy (at most 2 prior regimens one of which must have been platinum-based) and with one small molecule EGFRI
Primary Outcome Measures
NameTimeMethod
Clinical efficacy based on the evaluation of objective tumor response rate (RR)until progressive disease or unacceptable toxicity.
Secondary Outcome Measures
NameTimeMethod
To investigate potential molecular markers predictive of clinical effectas long as patients are in the study
To assess additional clinical efficacy of RAD001as long as patients are in the study
To assess the steady state levels of RAD001 in bloodas long as patients are in the study
To assess safety of RAD001 monotherapyas long as patients are in the study

Trial Locations

Locations (2)

Nevada Cancer Institute

🇺🇸

Las Vegas, Nevada, United States

MD Anderson Cancer Center, Department of Thoracic /Head and Neck Medical Oncology

🇺🇸

Houston, Texas, United States

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