Clinical trial NCT00600015: Sorafenib/Erlotinib Versus Erlotinib Alone in Previously Treated Advanced Non-Small-Cell Lung Cancer (NSCLC)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
Advanced
Sorafenib
Erlotinib
Double-blind
Placebo-controlled
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2008-01-24
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Objective Response Rate (ORR)
timeFrame: 18 months
measure: Progression Free Survival (PFS)
timeFrame: 18 months
measure: Disease Control Rate (DCR)
timeFrame: 18 months
Secondary outcomes:
measure: Duration of Response
timeFrame: 18 months
measure: 6-month PFS
timeFrame: 6 months
measure: Overall Survival (OS)
timeFrame: 18 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Marietta
country: United States
facility: Wellstar Cancer Research
state: Georgia
city: Overland Park
country: United States
facility: Kansas City Cancer Centers
state: Kansas
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Omaha
country: United States
facility: Methodist Cancer Center
state: Nebraska
city: Asheville
country: United States
facility: Cancer Care of Western North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Columbus
country: United States
facility: Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center
state: Ohio
city: Columbia
country: United States
facility: South Carolina Oncology Associates, PA
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Collierville
country: United States
facility: Family Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Corpus Christi
country: United States
facility: Coastal Bend Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: David Spigel, M.D.
role: STUDY_CHAIR
References:
citation: 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.