Clinical trial NCT00124280: Study Investigating the Effect of Everolimus Monotherapy in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small-cell Lung Carcinoma
Keywords: Lung cancer
non-small cell
everolimus
Non-small cell lung cancer (NSCLC)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-07-27
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Clinical efficacy based on the evaluation of objective tumor response rate (RR)
timeFrame: until progressive disease or unacceptable toxicity.
Secondary outcomes:
measure: To assess safety of RAD001 monotherapy
timeFrame: as long as patients are in the study
measure: To assess additional clinical efficacy of RAD001
timeFrame: as long as patients are in the study
measure: To assess the steady state levels of RAD001 in blood
timeFrame: as long as patients are in the study
measure: To investigate potential molecular markers predictive of clinical effect
timeFrame: as long as patients are in the study
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Houston
country: United States
facility: MD Anderson Cancer Center, Department of Thoracic /Head and Neck Medical Oncology
state: Texas
Study officials:
affiliation: Novartis Pharmaceutcals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: White DA, Schwartz LH, Dimitrijevic S, Scala LD, Hayes W, Gross SH. Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001). J Thorac Oncol. 2009 Nov;4(11):1357-63. doi: 10.1097/JTO.0b013e3181ba20b1.
citation: Soria JC, Shepherd FA, Douillard JY, Wolf J, Giaccone G, Crino L, Cappuzzo F, Sharma S, Gross SH, Dimitrijevic S, Di Scala L, Gardner H, Nogova L, Papadimitrakopoulou V. Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors. Ann Oncol. 2009 Oct;20(10):1674-81. doi: 10.1093/annonc/mdp060. Epub 2009 Jun 23.