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

Non-small-cell Lung Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00124280
• Other study ID #: CRAD001C2235
• Status: Completed
• Phase: Phase 2
• First received: July 26, 2005
• Last updated: November 16, 2016
• Start date: July 2005

Study information

• Verified date: November 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small-cell Lung Carcinoma

Intervention

Drug:
• RAD001

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center, Department of Thoracic /Head and Neck Medical Oncology	Houston	Texas
United States	Nevada Cancer Institute	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 wi — View 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.0b013e3181b — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical efficacy based on the evaluation of objective tumor response rate (RR)		until progressive disease or unacceptable toxicity.	No
Secondary	To assess safety of RAD001 monotherapy		as long as patients are in the study	Yes
Secondary	To assess additional clinical efficacy of RAD001		as long as patients are in the study	Yes
Secondary	To assess the steady state levels of RAD001 in blood		as long as patients are in the study	Yes
Secondary	To investigate potential molecular markers predictive of clinical effect		as long as patients are in the study	Yes

External Links

•   Results for CRAD001C2235 from the Novartis Clinical Trials Website