Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00064350
• Other study ID #: CDR0000315383
• Secondary ID: E2501U10CA021115
• Status: Completed
• Phase: Phase 2
• Start date: June 28, 2004
• Est. completion date: March 2011

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 That is, tumor growth is suspended while the drug is administered but returns to baseline rates when the agent is withdrawn.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.

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 information / eligibility

• Status: Completed
• Enrollment: 342
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Sorafenib
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.
• Placebo
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).

Locations

Country	Name	City	State
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Fox Valley Hematology and Oncology - East Grant Street	Appleton	Wisconsin
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia
United States	Christ Hospital Cancer Center	Cincinnati	Ohio
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	UT Southwestern University Hospital - Zale Lipshy	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	Easton Regional Cancer Center at Easton Hospital	Easton	Pennsylvania
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Alexian Brothers Radiation Oncology	Elk Grove Village	Illinois
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Community Hospital	Eureka	Illinois
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Foote Hospital	Jackson	Michigan
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kewanee Hospital	Kewanee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Baptist Regional Cancer Center at Baptist Hospital of East Tennessee	Knoxville	Tennessee
United States	Howard Community Hospital	Kokomo	Indiana
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Clarian Arnett Cancer Care	Lafayette	Indiana
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Central Pennsylvania Hematology and Medical Oncology Associates, PC	Lemoyne	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Southwest Medical Center	Liberal	Kansas
United States	St. Rita's Medical Center	Lima	Ohio
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McDonough District Hospital	Macomb	Illinois
United States	Dean Medical Center - Madison	Madison	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	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Somerset Medical Center	Somerville	New Jersey
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Stanford Comprehensive Cancer Center - Stanford	Stanford	California
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Morton Hospital & Medical Center	Taunton	Massachusetts
United States	North Suburban Medical Center	Thornton	Colorado
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-free Survival	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.	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.
Secondary	Overall Survival	Overall survival is defined as the duration from randomization to death or last known alive. Only randomized patients were included in this analysis.	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
Secondary	Best Overall Response	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.	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