Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer
A Double Blind Phase II Study of BAY 43-9006 in Patients With Non-Small Cell Lung Cancer Who Have Failed at Least Two Prior Chemotherapy Regimens
3 other identifiers
interventional
342
1 country
141
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 That is, tumor growth is suspended while the drug is administered but returns to baseline rates when the agent is withdrawn.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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 lung-cancer
Started Jun 2004
Typical duration for phase_2 lung-cancer
141 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 8, 2003
CompletedFirst Posted
Study publicly available on registry
July 9, 2003
CompletedStudy Start
First participant enrolled
June 28, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2011
CompletedResults Posted
Study results publicly available
November 28, 2012
CompletedJune 29, 2023
June 1, 2023
6.7 years
July 8, 2003
March 8, 2012
June 14, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Patients Maintaining Stable Disease or Objective Response 2 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
Two months after randomization
Secondary Outcomes (3)
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.
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
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
Study Arms (3)
Induction then Sorafenib
EXPERIMENTALInduction: 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 then Placebo then Sorafenib
PLACEBO COMPARATORInduction: 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, not randomized
OTHERInduction: 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.
Interventions
Step 1 (induction): Sorafenib was giventwice daily for two cycles to all patients. Patients with progression (PD) discontinued treatment. Those who responded after two cycles continued treatment up to 1 year or until PD. With response after 1 year, patients were given the option to continue treatment until PD. Patients who were stable after the end of induction were then randomized onto Step 2 to either continue sorafenib or receive placebo. Step 2 (randomization): Patients with stable disease after induction will be randomized in a double-blinded manner to placebo or sorafenib. If a patient has progressed, the arm will be unblinded. Patients on placebo with PD can then crossover to receive sorafenib; patients with PD on the sorafenib arm will be removed from the study. Step 3 (crossover): If patients on placebo progressed within 1 year from randomization, they crossed over to the treatment arm and receive sorafenib for up to 1 year or until PD, unacceptable toxicity, or death.
Patients randomized to the placebo arm in step 2 continued receiving placebo until disease progression or one year from randomization. Placebo was given orally twice a day (BID).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (141)
Stanford Comprehensive Cancer Center - Stanford
Stanford, California, 94305, United States
Aurora Presbyterian Hospital
Aurora, Colorado, 80012, United States
Boulder Community Hospital
Boulder, Colorado, 80301-9019, United States
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, 80933, United States
Porter Adventist Hospital
Denver, Colorado, 80210, United States
Presbyterian - St. Luke's Medical Center
Denver, Colorado, 80218, United States
St. Joseph Hospital
Denver, Colorado, 80218, United States
Rose Medical Center
Denver, Colorado, 80220, United States
CCOP - Colorado Cancer Research Program
Denver, Colorado, 80224-2522, United States
Swedish Medical Center
Englewood, Colorado, 80110, United States
Front Range Cancer Specialists
Fort Collins, Colorado, 80528, United States
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
Grand Junction, Colorado, 81502, United States
Sky Ridge Medical Center
Lone Tree, Colorado, 80124, United States
Hope Cancer Care Center at Longmont United Hospital
Longmont, Colorado, 80502, United States
St. Mary - Corwin Regional Medical Center
Pueblo, Colorado, 81004, United States
North Suburban Medical Center
Thornton, Colorado, 80229, United States
Baptist Cancer Institute - Jacksonville
Jacksonville, Florida, 32207, United States
Rush-Copley Cancer Care Center
Aurora, Illinois, 60507, United States
St. Joseph Medical Center
Bloomington, Illinois, 61701, United States
Graham Hospital
Canton, Illinois, 61520, United States
Memorial Hospital
Carthage, Illinois, 62321, United States
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, 62526, United States
Alexian Brothers Radiation Oncology
Elk Grove Village, Illinois, 60007, United States
Eureka Community Hospital
Eureka, Illinois, 61530, United States
Galesburg Clinic, PC
Galesburg, Illinois, 61401, United States
Galesburg Cottage Hospital
Galesburg, Illinois, 61401, United States
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Mason District Hospital
Havana, Illinois, 62644, United States
Hinsdale Hematology Oncology Associates
Hinsdale, Illinois, 60521, United States
Hopedale Medical Complex
Hopedale, Illinois, 61747, United States
Joliet Oncology-Hematology Associates, Limited - West
Joliet, Illinois, 60435, United States
Kewanee Hospital
Kewanee, Illinois, 61443, United States
McDonough District Hospital
Macomb, Illinois, 61455, United States
BroMenn Regional Medical Center
Normal, Illinois, 61761, United States
Community Cancer Center
Normal, Illinois, 61761, United States
Community Hospital of Ottawa
Ottawa, Illinois, 61350, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
Ottawa, Illinois, 61350, United States
Cancer Treatment Center at Pekin Hospital
Pekin, Illinois, 61554, United States
Proctor Hospital
Peoria, Illinois, 61614, United States
CCOP - Illinois Oncology Research Association
Peoria, Illinois, 61615, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, 61615, United States
Methodist Medical Center of Illinois
Peoria, Illinois, 61636, United States
OSF St. Francis Medical Center
Peoria, Illinois, 61637, United States
Illinois Valley Community Hospital
Peru, Illinois, 61354, United States
Perry Memorial Hospital
Princeton, Illinois, 61356, United States
Swedish-American Regional Cancer Center
Rockford, Illinois, 61104-2315, United States
St. Margaret's Hospital
Spring Valley, Illinois, 61362, United States
Carle Cancer Center at Carle Foundation Hospital
Urbana, Illinois, 61801, United States
CCOP - Carle Cancer Center
Urbana, Illinois, 61801, United States
Elkhart General Hospital
Elkhart, Indiana, 46515, United States
Howard Community Hospital
Kokomo, Indiana, 46904, United States
Center for Cancer Therapy at LaPorte Hospital and Health Services
La Porte, Indiana, 46350, United States
Clarian Arnett Cancer Care
Lafayette, Indiana, 47904, United States
Saint Anthony Memorial Health Centers
Michigan City, Indiana, 46360, United States
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, 46601, United States
Memorial Hospital of South Bend
South Bend, Indiana, 46601, United States
Saint Joseph Regional Medical Center
South Bend, Indiana, 46617, United States
Cedar Rapids Oncology Associates
Cedar Rapids, Iowa, 52403, United States
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, 51101, United States
Mercy Medical Center - Sioux City
Sioux City, Iowa, 51104, United States
St. Luke's Regional Medical Center
Sioux City, Iowa, 51104, United States
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, 66720, United States
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, 67801, United States
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, 67042, United States
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, 67068, United States
Southwest Medical Center
Liberal, Kansas, 67901, United States
Cancer Center of Kansas, PA - Newton
Newton, Kansas, 67114, United States
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, 67357, United States
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, 67124, United States
Cancer Center of Kansas, PA - Salina
Salina, Kansas, 67042, United States
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, 67152, United States
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, 67208, United States
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, 67214, United States
CCOP - Wichita
Wichita, Kansas, 67214, United States
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, 67214, United States
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, 67156, United States
Morton Hospital & Medical Center
Taunton, Massachusetts, 02780, United States
Saint Joseph Mercy Cancer Center
Ann Arbor, Michigan, 48106-0995, United States
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, 48106, United States
Genesys Hurley Cancer Institute
Flint, Michigan, 48503, United States
Hurley Medical Center
Flint, Michigan, 48503, United States
Foote Hospital
Jackson, Michigan, 49201, United States
Borgess Medical Center
Kalamazoo, Michigan, 49001, United States
West Michigan Cancer Center
Kalamazoo, Michigan, 49007-3731, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
Lakeland Regional Cancer Care Center - St. Joseph
Saint Joseph, Michigan, 49085, United States
Fairview Ridges Hospital
Burnsville, Minnesota, 55337, United States
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, 55432, United States
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, 55109, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, 55422-2900, United States
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, 55416, United States
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, 55416, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, 55125, United States
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102, United States
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, 89106, United States
Veterans Affairs Medical Center - East Orange
East Orange, New Jersey, 07018-1095, United States
Somerset Medical Center
Somerville, New Jersey, 08876, United States
Our Lady of Mercy Medical Center Comprehensive Cancer Center
The Bronx, New York, 10466, United States
Aultman Cancer Center at Aultman Hospital
Canton, Ohio, 44710-1799, United States
Christ Hospital Cancer Center
Cincinnati, Ohio, 45219, United States
Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065, United States
MetroHealth Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
St. Rita's Medical Center
Lima, Ohio, 45801, United States
St. Luke's Cancer Network at St. Luke's Hospital
Bethlehem, Pennsylvania, 18015, United States
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, 19010, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822-0001, United States
Easton Regional Cancer Center at Easton Hospital
Easton, Pennsylvania, 18042, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
Central Pennsylvania Hematology and Medical Oncology Associates, PC
Lemoyne, Pennsylvania, 17043, United States
Lewistown Hospital
Lewistown, Pennsylvania, 17044, United States
Cancer Center of Paoli Memorial Hospital
Paoli, Pennsylvania, 19301-1792, United States
Joan Karnell Cancer Center at Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107, United States
Geisinger Medical Group - Scenery Park
State College, Pennsylvania, 16801, United States
Mount Nittany Medical Center
State College, Pennsylvania, 16803, United States
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, 18711, United States
CCOP - MainLine Health
Wynnewood, Pennsylvania, 19096, United States
Lankenau Cancer Center at Lankenau Hospital
Wynnewood, Pennsylvania, 19096, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105, United States
Medical X-Ray Center, PC
Sioux Falls, South Dakota, 57105, United States
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, 57117-5039, United States
Baptist Regional Cancer Center at Baptist Hospital of East Tennessee
Knoxville, Tennessee, 37901, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838, United States
UT Southwestern University Hospital - Zale Lipshy
Dallas, Texas, 75235, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, 75390, United States
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
Charleston, West Virginia, 25304, United States
Fox Valley Hematology and Oncology - East Grant Street
Appleton, Wisconsin, 54911-3496, United States
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54301-3526, United States
Green Bay Oncology, Limited at St. Mary's Hospital
Green Bay, Wisconsin, 54303, United States
St. Mary's Hospital Medical Center - Green Bay
Green Bay, Wisconsin, 54303, United States
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54307-3508, United States
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
Dean Medical Center - Madison
Madison, Wisconsin, 53717, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, 53792-6164, United States
Holy Family Memorial Medical Center Cancer Care Center
Manitowoc, Wisconsin, 54221-1450, United States
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, 54143, United States
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, 54449, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Statistician
- Organization
- Eastern Cooperative Oncology Group (ECOG) Statistical Office
Study Officials
- STUDY CHAIR
Joan H. Schiller, MD
Simmons Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 8, 2003
First Posted
July 9, 2003
Study Start
June 28, 2004
Primary Completion
March 1, 2011
Study Completion
March 1, 2011
Last Updated
June 29, 2023
Results First Posted
November 28, 2012
Record last verified: 2023-06