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

NCT00600015 | Completed Phase 2 Results

• 1 other identifier: SCRI LUN 160
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 16

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; Advanced; Sorafenib; Erlotinib; Double-blind; Placebo-controlled

Outcome Measures

Primary Outcomes (3)

• Overall Objective Response Rate (ORR)

  Overall response rate (ORR) is defined as the percentage of patients who have a partial or complete response to therapy. Responses were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0). Complete Response: Disappearance of all target lesions, and disappearance of all non-target lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions (taking as reference the baseline sum of longest diameters)

  18 months

• Progression Free Survival (PFS)

  Progression-free survival is defined as the time from the first day of treatment until the day tumor progression was documented. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions

  18 months

• Disease Control Rate (DCR)

  Disease Control Rate (DCR) is defined as the percentage of patients who have a partial/complete/stable response to therapy. Responses were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0). Complete Response: Disappearance of all target lesions, and disappearance of all non-target lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions (taking as reference the baseline sum of longest diameters) Stable Response: Neither sufficient shrinkage to qualify for partial response, nor sufficient increase to qualify for progressive disease (taking as reference the smallest sum of diameters since the treatment started).

  18 months

Secondary Outcomes (3)

• Duration of Response

  18 months

• 6-month PFS

  6 months

• Overall Survival (OS)

  18 months

Study Arms (2)

Combination Therapy

EXPERIMENTAL

Erlotinib + Sorafenib

Drug: Erlotinib + Sorafenib

Placebo

PLACEBO COMPARATOR

Erlotinib + Placebo

Drug: Erlotinib + Placebo

Interventions

Erlotinib + Sorafenib 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.

Also known as: Tarceva, Nexavar

Combination Therapy

Erlotinib + Placebo DRUG

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

Also known as: Tarceva

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Bayer: collaborator

Study Sites (16)

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Wellstar Cancer Research

Marietta, Georgia, 30060, United States

Location

Kansas City Cancer Centers

Overland Park, Kansas, 66210, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Cancer Care of Western North Carolina

Asheville, North Carolina, 28801, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

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

Columbus, Ohio, 43219, United States

Location

South Carolina Oncology Associates, PA

Columbia, South Carolina, 29210, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Family Cancer Center

Collierville, Tennessee, 38017, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Coastal Bend Cancer Center

Corpus Christi, Texas, 78463, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23235, United States

Location

Related Publications (1)

• 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.

  PMID: 21576636 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Sorafenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: John D. Hainsworth, MD
• Organization: Sarah Cannon Research Institute

ASKSARAH@scresearch.net

877-691-7274

Study Officials

• David Spigel, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 24, 2008
• Study Start: February 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: March 10, 2022
• Results First Posted: September 21, 2012

Record last verified: 2022-02

Locations

US (16)