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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00124280

Collaborator

(none)

Enrollment

Locations

Arms

42.5

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small-cell Lung Carcinoma	Drug: RAD001	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

85 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: previously treated with chemotherapy only patients previously treated with chemotherapy only (at most 2 prior regimens one of which must have been platinum-based) and no EGFRI	Drug: RAD001 Other Names: Everolimus
Experimental: previously treated with chemotherapy + small 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 Other Names: Everolimus

Arm

Intervention/Treatment

Experimental: previously treated with chemotherapy only

patients previously treated with chemotherapy only (at most 2 prior regimens one of which must have been platinum-based) and no EGFRI

Drug: RAD001

Other Names:

Everolimus

Experimental: previously treated with chemotherapy + small

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

Other Names:

Everolimus

Outcome Measures

Primary Outcome Measures

Clinical efficacy based on the evaluation of objective tumor response rate (RR) [until progressive disease or unacceptable toxicity.]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
2	MD Anderson Cancer Center, Department of Thoracic /Head and Neck Medical Oncology	Houston	Texas	United States	77030