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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00124280
First received: July 26, 2005
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

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 Intervention Phase
Non-small-cell Lung Carcinoma
Drug: RAD001
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Clinical efficacy based on the evaluation of objective tumor response rate (RR) [ Time Frame: until progressive disease or unacceptable toxicity. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess safety of RAD001 monotherapy [ Time Frame: as long as patients are in the study ] [ Designated as safety issue: Yes ]
  • To assess additional clinical efficacy of RAD001 [ Time Frame: as long as patients are in the study ] [ Designated as safety issue: Yes ]
  • To assess the steady state levels of RAD001 in blood [ Time Frame: as long as patients are in the study ] [ Designated as safety issue: Yes ]
  • To investigate potential molecular markers predictive of clinical effect [ Time Frame: as long as patients are in the study ] [ Designated as safety issue: Yes ]

Enrollment: 85
Study Start Date: July 2005
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Everolimus

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00124280

Locations
United States, Nevada
Nevada Cancer Institute
Las Vegas, Nevada, United States, 89135
United States, Texas
MD Anderson Cancer Center, Department of Thoracic /Head and Neck Medical Oncology
Houston, Texas, United States, 77030
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceutcals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00124280     History of Changes
Other Study ID Numbers: CRAD001C2235
Study First Received: July 26, 2005
Last Updated: November 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Lung cancer
non-small cell
everolimus
Non-small cell lung cancer (NSCLC)

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 01, 2014