Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer
- Registration Number
- NCT00064350
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
RATIONALE: Preclinical studies indicate that sorafenib is a potent inhibitor of Raf kinase in vitro and in vivo, with significant dose-dependent, anti-tumor activity in four different human tumor types including colon, pancreatic, lung, and ovarian. This activity was cytostatic in nature and was maintained if dosing was continued. That is, tumor growth is suspended while the drug is administered but returns to baseline rates when the agent is withdrawn. Therefore, the optimal schedule will be an uninterrupted one. To assess the activity of sorafenib in a timely manner and with a meaningful interpretation, a randomized discontinuation design was adopted in the present trial, conducted in a population who were potentially sensitive to sorafenib.
PURPOSE: This randomized phase II trial is studying sorafenib to see how well it works compared to placebo in treating patients with refractory non-small cell lung cancer.
- Detailed Description
OBJECTIVES:
* To determine the percent of patients maintaining stable disease or objective response two months after randomization with continued sorafenib treatment, compared to patients switched to placebo.
* To determine progression-free survival, overall survival, and response rate.
OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to number of prior chemotherapy regimens (2 vs more than 2) and prior epidermal growth factor receptor inhibitor treatment (yes vs no).
* Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.
* Randomization: Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients who develop disease progression within 1 year after randomization cross over to arm I.
Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 311 patients will be accrued for this study within approximately 3 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 342
- Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC)
- Disease must have progressed after at least 2 prior chemotherapy regimens for NSCLC
- Patients must have measurable or nonmeasurable disease
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- AST and ALT no greater than 3 times ULN (5 times ULN in patients with liver disease)
- Creatinine less than 1.5 times ULN or calculated creatinine clearance greater than 50 mL/min
- More than 3 weeks since prior chemotherapy, radiotherapy, immunotherapy or other investigational drug use
- Recovered from all prior therapy
- Fertile patients must use effective contraception
- Age >= 18
- ECOG performance status of 0-1
-
Prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable and off therapy for at least 2 months
-
Active second malignancy
-
Clinically evident congestive heart failure, serious cardiac arrhythmias, or symptoms of coronary heart disease
-
Prior radiotherapy to the only site of measurable or evaluable disease unless there is evidence of disease progression in that site
-
Prior exposure to a ras pathway inhibitor (e.g., farnesyl transferase inhibitor)
-
Concurrent medications known to be metabolized by the liver with a narrow therapeutic index, including the following:
- Ketoconazole
- Itraconazole
- Quinidine
- Digoxin
- Cyclosporine
- Ritonavir
- Grapefruit products
- Carbamazepine
- Phenytoin
- Phenobarbital
-
Pregnant or nursing
-
Clinically serious active infection
-
Medical conditions, substance abuse or psychological/social situation that would preclude study participation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Induction then Placebo then Sorafenib Placebo Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression. Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the placebo arm receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients on the placebo arm who develop disease progression within 1 year after randomization may cross over to sorafenib arm. Induction then Placebo then Sorafenib Sorafenib Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression. Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the placebo arm receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients on the placebo arm who develop disease progression within 1 year after randomization may cross over to sorafenib arm. Induction then Sorafenib Sorafenib Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression. Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the sorafenib arm receive sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable disease. Induction, not randomized Sorafenib Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Post-induction: Patients with responding disease or disease progression were not randomized in Step 2. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression, while patients with disease progression were removed from the study.
- Primary Outcome Measures
Name Time Method Number of Patients Maintaining Stable Disease or Objective Response 2 Months After Randomization Two months after randomization Per RECIST Criteria (V1.0):
Complete Response (CR): disappearance of all target lesions Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions Progressive Disease (PD): \>=20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of longest diameter recorded since randomization, or the appearance of new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD
- Secondary Outcome Measures
Name Time Method Progression-free Survival Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years. Progression-free survival is defined as the duration from randomization to disease progression or death, whichever occurs first. Only randomized patients were included in this analysis.
Overall Survival Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years Overall survival is defined as the duration from randomization to death or last known alive. Only randomized patients were included in this analysis.
Best Overall Response Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years The best overall response is the best response (per RECIST 1.0) recorded from randomization until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since randomization.
Trial Locations
- Locations (141)
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
St. Mary - Corwin Regional Medical Center
🇺🇸Pueblo, Colorado, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Aultman Cancer Center at Aultman Hospital
🇺🇸Canton, Ohio, United States
Joan Karnell Cancer Center at Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Swedish-American Regional Cancer Center
🇺🇸Rockford, Illinois, United States
St. Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Saint Anthony Memorial Health Centers
🇺🇸Michigan City, Indiana, United States
Center for Cancer Therapy at LaPorte Hospital and Health Services
🇺🇸La Porte, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Cedar Rapids Oncology Associates
🇺🇸Cedar Rapids, Iowa, United States
Illinois Valley Community Hospital
🇺🇸Peru, Illinois, United States
CCOP - Northern Indiana CR Consortium
🇺🇸South Bend, Indiana, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Mercy Medical Center - Sioux City
🇺🇸Sioux City, Iowa, United States
Howard Community Hospital
🇺🇸Kokomo, Indiana, United States
St. Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Clarian Arnett Cancer Care
🇺🇸Lafayette, Indiana, United States
Somerset Medical Center
🇺🇸Somerville, New Jersey, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
UT Southwestern University Hospital - Zale Lipshy
🇺🇸Dallas, Texas, United States
Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
Our Lady of Mercy Medical Center Comprehensive Cancer Center
🇺🇸Bronx, New York, United States
Medical X-Ray Center, PC
🇺🇸Sioux Falls, South Dakota, United States
St. Luke's Cancer Network at St. Luke's Hospital
🇺🇸Bethlehem, Pennsylvania, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
St. Rita's Medical Center
🇺🇸Lima, Ohio, United States
Easton Regional Cancer Center at Easton Hospital
🇺🇸Easton, Pennsylvania, United States
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
MetroHealth Cancer Care Center at MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Foote Hospital
🇺🇸Jackson, Michigan, United States
Lakeland Regional Cancer Care Center - St. Joseph
🇺🇸Saint Joseph, Michigan, United States
Veterans Affairs Medical Center - East Orange
🇺🇸East Orange, New Jersey, United States
Central Pennsylvania Hematology and Medical Oncology Associates, PC
🇺🇸Lemoyne, Pennsylvania, United States
Green Bay Oncology, Limited at St. Mary's Hospital
🇺🇸Green Bay, Wisconsin, United States
Minnesota Oncology Hematology, PA - Woodbury
🇺🇸Woodbury, Minnesota, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Dean Medical Center - Madison
🇺🇸Madison, Wisconsin, United States
CCOP - MainLine Health
🇺🇸Wynnewood, Pennsylvania, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
🇺🇸Charleston, West Virginia, United States
Fox Valley Hematology and Oncology - East Grant Street
🇺🇸Appleton, Wisconsin, United States
Bay Area Cancer Care Center at Bay Area Medical Center
🇺🇸Marinette, Wisconsin, United States
Lewistown Hospital
🇺🇸Lewistown, Pennsylvania, United States
Lankenau Cancer Center at Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
Cancer Center of Kansas, PA - Wellington
🇺🇸Wellington, Kansas, United States
Cancer Center of Kansas, PA - Chanute
🇺🇸Chanute, Kansas, United States
Cancer Center of Kansas, PA - El Dorado
🇺🇸El Dorado, Kansas, United States
Cancer Center of Kansas, PA - Winfield
🇺🇸Winfield, Kansas, United States
Cancer Center of Kansas, PA - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas, PA - Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Salina
🇺🇸Salina, Kansas, United States
Cancer Center of Kansas, PA - Wichita
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Kingman
🇺🇸Kingman, Kansas, United States
Southwest Medical Center
🇺🇸Liberal, Kansas, United States
Cancer Center of Kansas, PA - Pratt
🇺🇸Pratt, Kansas, United States
Via Christi Cancer Center at Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Dodge City
🇺🇸Dodge City, Kansas, United States
Cancer Center of Kansas, PA - Parsons
🇺🇸Parsons, Kansas, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
St. Joseph Hospital
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
CCOP - Colorado Cancer Research Program
🇺🇸Denver, Colorado, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Alexian Brothers Radiation Oncology
🇺🇸Elk Grove Village, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
🇺🇸Ottawa, Illinois, United States
Stanford Comprehensive Cancer Center - Stanford
🇺🇸Stanford, California, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
Front Range Cancer Specialists
🇺🇸Fort Collins, Colorado, United States
Baptist Cancer Institute - Jacksonville
🇺🇸Jacksonville, Florida, United States
Hope Cancer Care Center at Longmont United Hospital
🇺🇸Longmont, Colorado, United States
North Suburban Medical Center
🇺🇸Thornton, Colorado, United States
Rush-Copley Cancer Care Center
🇺🇸Aurora, Illinois, United States
Decatur Memorial Hospital Cancer Care Institute
🇺🇸Decatur, Illinois, United States
Eureka Community Hospital
🇺🇸Eureka, Illinois, United States
Galesburg Clinic, PC
🇺🇸Galesburg, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Ingalls Cancer Care Center at Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Hopedale Medical Complex
🇺🇸Hopedale, Illinois, United States
McDonough District Hospital
🇺🇸Macomb, Illinois, United States
Hinsdale Hematology Oncology Associates
🇺🇸Hinsdale, Illinois, United States
Community Cancer Center
🇺🇸Normal, Illinois, United States
BroMenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Community Hospital of Ottawa
🇺🇸Ottawa, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸Peoria, Illinois, United States
Cancer Treatment Center at Pekin Hospital
🇺🇸Pekin, Illinois, United States
CCOP - Illinois Oncology Research Association
🇺🇸Peoria, Illinois, United States
OSF St. Francis Medical Center
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Saint Joseph Regional Medical Center
🇺🇸South Bend, Indiana, United States
Morton Hospital & Medical Center
🇺🇸Taunton, Massachusetts, United States
Minnesota Oncology Hematology, PA - Maplewood
🇺🇸Maplewood, Minnesota, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Cancer Center of Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
Mount Nittany Medical Center
🇺🇸State College, Pennsylvania, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
Geisinger Medical Group - Scenery Park
🇺🇸State College, Pennsylvania, United States
Baptist Regional Cancer Center at Baptist Hospital of East Tennessee
🇺🇸Knoxville, Tennessee, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
St. Mary's Hospital Medical Center - Green Bay
🇺🇸Green Bay, Wisconsin, United States
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Holy Family Memorial Medical Center Cancer Care Center
🇺🇸Manitowoc, Wisconsin, United States
Graham Hospital
🇺🇸Canton, Illinois, United States
Aurora Presbyterian Hospital
🇺🇸Aurora, Colorado, United States
Saint Joseph Mercy Cancer Center
🇺🇸Ann Arbor, Michigan, United States
CCOP - Michigan Cancer Research Consortium
🇺🇸Ann Arbor, Michigan, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸Colorado Springs, Colorado, United States
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
🇺🇸Grand Junction, Colorado, United States
St. Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
Joliet Oncology-Hematology Associates, Limited - West
🇺🇸Joliet, Illinois, United States
Kewanee Hospital
🇺🇸Kewanee, Illinois, United States
Carle Cancer Center at Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
CCOP - Wichita
🇺🇸Wichita, Kansas, United States