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

NCT00124280 | Completed Phase 2

• 1 other identifier: CRAD001C2235
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-small-cell Lung Carcinoma

Keywords

Lung cancer; non-small cell; everolimus; Non-small cell lung cancer (NSCLC)

Outcome Measures

Primary Outcomes (1)

• Clinical efficacy based on the evaluation of objective tumor response rate (RR)

  until progressive disease or unacceptable toxicity.

Secondary Outcomes (4)

• 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

Study Arms (2)

previously treated with chemotherapy only

EXPERIMENTAL

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

Drug: RAD001

previously treated with chemotherapy + small

EXPERIMENTAL

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

Interventions

RAD001 DRUG

Also known as: Everolimus

previously treated with chemotherapy + small; previously treated with chemotherapy only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Nevada Cancer Institute

Las Vegas, Nevada, 89135, United States

Location

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

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 19745764 RESULT

• 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.

  PMID: 19549709 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceutcals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2005
• First Posted: July 27, 2005
• Study Start: July 1, 2005
• Primary Completion: October 1, 2007
• Last Updated: November 18, 2016

Record last verified: 2016-11

Locations

US (2)