Sorafenib/Erlotinib Versus Erlotinib Alone in Previously Treated Advanced Non-Small-Cell Lung Cancer (NSCLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00600015
Recruitment Status : Completed
First Posted : January 24, 2008
Results First Posted : September 21, 2012
Last Update Posted : September 21, 2012
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
This trial will investigate the use of the newer targeted agents erlotinib and sorafenib in patients with stage IIIB or stage IV NSCLC who have received 1-2 prior chemotherapy regimens. Patients will be randomized to receive erlotinib (150 mg/day) and sorafenib (400 mg twice daily), or erlotinib (150 mg/day) and a placebo.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Erlotinib + Sorafenib Drug: Erlotinib + Placebo Phase 2

Detailed Description:
The rationale of this study is to combine two distinct kinase inhibitors to evaluate synergistic inhibition of angiogenesis and epidermal growth factor receptor (EGFR) signaling. Erlotinib is a oral tyrosine kinase inhibitor that targets EGFR. Sorafenib is a oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor beta, Raf-1, Flt-3, and C-kit. These agents also do not exhibit overlapping adverse event profiles which provided additional support for studying this combination therapy.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 166 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind Placebo-Controlled Phase II Trial of Sorafenib and Erlotinib or Erlotinib Alone in Previously Treated Advanced Non-Small Cell Lung Cancer
Study Start Date : February 2008
Actual Primary Completion Date : February 2009
Actual Study Completion Date : February 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Combination Therapy
Erlotinib + Sorafenib
Drug: Erlotinib + Sorafenib
Patients who are randomized to Cohort A will take sorafenib 400 mg (2 x 200-mg tablets) orally twice a day, and erlotinib 150 mg orally once a day.
Other Names:
  • Tarceva
  • Nexavar
Placebo Comparator: Placebo
Erlotinib + Placebo
Drug: Erlotinib + Placebo
Patients who are randomized to Cohort B will take erlotinib 150 mg orally once a day and placebo orally twice a day.
Other Name: Tarceva

Primary Outcome Measures :
  1. Overall Objective Response Rate (ORR) [ Time Frame: 18 months ]
  2. Progression Free Survival (PFS) [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: 18 months ]
  2. Duration of Response [ Time Frame: 18 months ]
  3. 6-month PFS [ Time Frame: 6 months ]
  4. Overall Survival (OS) [ Time Frame: 18 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed locally advanced or metastatic NSCLC (unresectable stage IIIB or stage IV). Eligible histologies include adenocarcinoma and squamous cell carcinoma. Patients with recurrent disease after treatment for localized NSCLC are also eligible. Cytologic specimens obtained by brushings, washings, or needle aspiration are acceptable.
  • At least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques, or as >= 10 mm with spiral computerized tomography (CT) scan according to the Response Evaluation Criteria in Solid Tumors (RECIST).
  • Failure of at least one, and no more than two prior cytotoxic chemotherapy regimens for advanced disease (either due to progressive disease or toxicity).
  • Recovery from any toxic effects of prior therapy to <= grade 1.
  • Completion of radiation therapy at least 28 days prior to the start of study treatment (not including palliative local radiation). Previously irradiated lesions in the advanced setting cannot be included as target lesions unless clear tumor progression has been observed since the end of radiation.
  • An ECOG performance status of 0-2.
  • Absolute neutrophil count (ANC) >= 1,500, platelets >= 75,000.
  • Hemoglobin >= 9 g/dL (within 7 days prior to study treatment).
  • International normalized ratio (INR) <= 1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution
  • Serum creatinine <= 1.5 x institutional upper limit of normal (ULN) within 7 days prior to study treatment.
  • Transaminases <= 3 x institutional ULN
  • Agreement of female patients of childbearing potential and male patients who have partners of childbearing potential to use an effective form of contraception to prevent pregnancy during treatment, and for a minimum of 90 days thereafter.
  • Patients who have treated brain metastases >= 4 weeks out (with surgery and/or radiation therapy) and no evidence of CNS progression.

Exclusion Criteria:

  • Past or current history of neoplasm (other than the entry diagnosis), with the exception of treated non-melanoma skin cancer or carcinoma in-situ of the cervix, or other cancers cured by local therapy alone, and a disease-free survival (DFS) >= 3 years.
  • Patients who have mixed tumors with small-cell elements are ineligible.
  • Pregnancy or lactation.
  • Prior treatment with EGFR TKIs or VEGFR TKIs for NSCLC. [NOTE: prior cetuximab and/or bevacizumab use is permitted].
  • Significant cardiac disease within 90 days of starting study treatment
  • Myocardial infarction within 6 months prior to initiation of study treatment.
  • Cardiomegaly on chest imaging or ventricular hypertrophy on electrocardiogram (ECG)
  • Poorly controlled hypertension
  • Unstable angina (anginal symptoms at rest).
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
  • A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  • A major surgical procedure, open biopsy, or significant traumatic injury within 28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.
  • Stroke or transient ischemic attack (TIA) within the past 6 months.
  • Any prior history of hypertensive crisis or hypertensive encephalopathy.
  • Pulmonary hemorrhage/bleeding event >= grade 2 within 28 days of study treatment.
  • Any other non-pulmonary hemorrhage/bleeding event >= grade 3 within 28 days of study treatment.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Serious non-healing wound, ulcer, or bone fracture.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00600015

United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
Wellstar Cancer Research
Marietta, Georgia, United States, 30060
United States, Kansas
Kansas City Cancer Centers
Overland Park, Kansas, United States, 66210
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, North Carolina
Cancer Care of Western North Carolina
Asheville, North Carolina, United States, 28801
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center
Columbus, Ohio, United States, 43219
United States, South Carolina
South Carolina Oncology Associates, PA
Columbia, South Carolina, United States, 29210
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Family Cancer Center
Collierville, Tennessee, United States, 38017
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
United States, Texas
Coastal Bend Cancer Center
Corpus Christi, Texas, United States, 78463
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23235
Sponsors and Collaborators
SCRI Development Innovations, LLC
Study Chair: David Spigel, M.D. SCRI Development Innovations, LLC

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT00600015     History of Changes
Other Study ID Numbers: SCRI LUN 160
First Posted: January 24, 2008    Key Record Dates
Results First Posted: September 21, 2012
Last Update Posted: September 21, 2012
Last Verified: August 2012

Keywords provided by SCRI Development Innovations, LLC:
Non-Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs