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

NCT ID: NCT00600015

Last Updated: 2022-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2009-02-28

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.

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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Combination Therapy

Erlotinib + Sorafenib

Group Type: EXPERIMENTAL

Erlotinib + Sorafenib

Intervention Type: DRUG

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.

Placebo

Erlotinib + Placebo

Group Type: PLACEBO_COMPARATOR

Erlotinib + Placebo

Intervention Type: DRUG

Patients who are randomized to Cohort B will take erlotinib 150 mg orally once a day and placebo orally twice a day.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Tarceva; Nexavar; Tarceva

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Spigel, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

Florida Cancer Specialists

Fort Myers, Florida, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Wellstar Cancer Research

Marietta, Georgia, United States

Kansas City Cancer Centers

Overland Park, Kansas, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Methodist Cancer Center

Omaha, Nebraska, United States

Cancer Care of Western North Carolina

Asheville, North Carolina, United States

Oncology Hematology Care

Cincinnati, Ohio, United States

Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center

Columbus, Ohio, United States

South Carolina Oncology Associates, PA

Columbia, South Carolina, United States

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States

Family Cancer Center

Collierville, Tennessee, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Coastal Bend Cancer Center

Corpus Christi, Texas, United States

Virginia Cancer Institute

Richmond, Virginia, United States

Countries

United States

References

Spigel DR, Burris HA 3rd, Greco FA, Shipley DL, Friedman EK, Waterhouse DM, Whorf RC, Mitchell RB, Daniel DB, Zangmeister J, Bass JD, Hainsworth JD. Randomized, double-blind, placebo-controlled, phase II trial of sorafenib and erlotinib or erlotinib alone in previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011 Jun 20;29(18):2582-9. doi: 10.1200/JCO.2010.30.7678. Epub 2011 May 16.

Reference Type: BACKGROUND

PMID: 21576636 (View on PubMed)

Other Identifiers

SCRI LUN 160

Identifier Type: -

Identifier Source: org_study_id