Bevacizumab and Sorafenib as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Liver Cancer
NCT ID: NCT00867321
Last Updated: 2022-04-19
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
24 participants
INTERVENTIONAL
2009-04-30
2013-05-31
Brief Summary
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PURPOSE: This randomized phase I/II trial is studying the best dose of bevacizumab when given together with sorafenib as first-line therapy in treating patients with locally advanced or metastatic liver cancer.(Phase I closed to accrual as of 11/03/2010)
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Detailed Description
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Primary
* Determine the maximum tolerated dose of bevacizumab in combination with sorafenib tosylate in patients with locally advanced or metastatic hepatocellular carcinoma. (Phase I closed to accrual as of 11/03/2010)
* Determine time to progression in these patients. (Phase II)
Secondary
* Determine the safety of this regimen in these patients. (Phase I closed to accrual as of 11/03/2010)
* Assess tolerability of this regimen in these patients. (Phase I closed to accrual as of 11/03/2010)
* Determine overall survival of these patients. (Phase II)
* Determine tumor response (at 6 months) in patients treated with this regimen. (Phase II)
* Determine progression-free survival of these patients. (Phase II)
* Determine response rate in patients treated with this regimen. (Phase II)
* Assess the occurrence of adverse events in these patients. (Phase II)
Tertiary
* Determine the relationship between tumor biomarkers and circulating biomarkers of vascular response and clinical outcome in patients treated with this regimen.
OUTLINE: This is a phase I, dose escalation study followed by a randomized phase II study.
* Phase I (closed to accrual as of 11/03/2010): Patients receive oral sorafenib tosylate twice daily on days 1-28 and bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
* Phase II: Patients are stratified according to gender (female vs male), ECOG performance status (0 vs 1), and Child-Pugh class (A vs B7). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive oral sorafenib tosylate on days 1-28 twice daily and bevacizumab IV on days 1 and 15.
* Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for analysis of circulating endothelial cells and circulating endothelial progenitor cells and angiogenic proteins in plasma by ELISA.
After completion of study treatment, patients are followed for 3 years.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm I (Phase II)
Patients receive oral sorafenib tosylate on days 1-28 twice daily and bevacizumab IV on days 1 and 15.
bevacizumab
Given IV
sorafenib tosylate
Given orally
Arm II (Phase II)
Patients receive oral sorafenib tosylate twice daily on days 1-28.
sorafenib tosylate
Given orally
Interventions
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bevacizumab
Given IV
sorafenib tosylate
Given orally
Eligibility Criteria
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Inclusion Criteria
* Histologically or cytologically confirmed hepatocellular carcinoma
* Locally advanced or metastatic disease that is not amenable to treatment with surgery or to orthotopic liver transplant
* Child Pugh class A or B7 disease
* Measurable disease
* No mixed cholangiocarcinoma/hepatocellular carcinoma
* No current or previously resected brain metastases
PATIENT CHARACTERISTICS:
* ECOG performance status 0-1
* Life expectancy ≥ 3 months
* ANC ≥ 1,200/mm³
* Platelet count ≥ 75,000/mm³
* Hemoglobin ≥ 9.0 g/dL
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST ≤ 5 times ULN
* Alkaline phosphatase ≤ 5 times ULN
* Urine protein ≤ 1+ by urine protein:creatinine ratio OR 24-hour urine protein \< 1 g
* QTc interval ≤ 500 msec on baseline EKG
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 2 weeks after sorafenib tosylate and 6 months after bevacizumab
* None of the following risk factors for decreased LVEF:
* Prior treatment with anthracyclines
* History of myocardial infarction within the past 12 months
* No uncontrolled hypertension (defined as systolic blood pressure \[BP\] \> 150 mm Hg or diastolic BP \> 100 mm Hg) despite optimal medical management
* No New York Heart Association class III-IV congestive heart failure
* No cardiac ventricular arrhythmias requiring antiarrhythmic therapy
* No history of hypertensive crisis or hypertensive encephalopathy
* No cardiac ventricular arrhythmia requiring anti-arrhythmic therapy within the past 6 months
* None of the following within the past 6 months:
* Transient ischemic attack
* Cerebrovascular accident
* Unstable angina or angina
* Clinically significant peripheral artery disease (i.e., claudication in less than one block) or any other arterial thrombotic event
* Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis
* No active or recent history of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within the past 30 days
* No evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation)
* No significant traumatic injury within the past 4 weeks
* No serious or non-healing wound, ulcer, or bone fracture
* No uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
* No other active malignancy within the past 3 years, except nonmelanotic skin cancer or carcinoma in situ of the cervix
* No comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or sorafenib tosylate
PRIOR CONCURRENT THERAPY:
* No prior systemic chemotherapy regimens for hepatocellular carcinoma
* No prior external beam radiation to the primary site
* No prior central thoracic radiation therapy (RT), including RT to the heart
* No prior radiation (if given for another malignancy) to ≥ 25% of the bone marrow
* At least 6 weeks since prior chemoembolization, radioembolization, radiofrequency ablation, or other local ablative therapies
* More than 4 weeks since prior biologic, hormonal, or immune therapy
* More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy
* More than 7 days since prior core biopsy or other minor surgical procedure (placement of a vascular access device allowed)
* No concurrent investigational agent which would be considered as a treatment for the primary neoplasm
* No concurrent anticoagulants, except low-dose warfarin or heparin for deep venous thrombosis prophylaxis
* No other concurrent treatment for prior malignancy (other than hormonal therapy)
18 Years
120 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Alliance for Clinical Trials in Oncology
OTHER
Responsible Party
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Principal Investigators
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Steven R. Alberts, MD
Role: STUDY_CHAIR
Mayo Clinic
Locations
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Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
Aurora Presbyterian Hospital
Aurora, Colorado, United States
Boulder Community Hospital
Boulder, Colorado, United States
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, United States
St. Anthony Central Hospital
Denver, Colorado, 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
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
Grand Junction, Colorado, United States
North Colorado Medical Center
Greeley, Colorado, United States
Sky Ridge Medical Center
Lone Tree, Colorado, United States
Hope Cancer Care Center at Longmont United Hospital
Longmont, Colorado, United States
McKee Medical Center
Loveland, Colorado, United States
St. Mary - Corwin Regional Medical Center
Pueblo, Colorado, United States
North Suburban Medical Center
Thornton, Colorado, United States
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, United States
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States
Illinois CancerCare - Bloomington
Bloomington, Illinois, United States
St. Joseph Medical Center
Bloomington, Illinois, United States
Graham Hospital
Canton, Illinois, United States
Illinois CancerCare - Canton
Canton, Illinois, United States
Illinois CancerCare - Carthage
Carthage, Illinois, United States
Memorial Hospital
Carthage, Illinois, United States
Eureka Community Hospital
Eureka, Illinois, United States
Illinois CancerCare - Eureka
Eureka, Illinois, United States
Galesburg Clinic, PC
Galesburg, Illinois, United States
Illinois CancerCare - Galesburg
Galesburg, Illinois, United States
Illinois CancerCare - Havana
Havana, Illinois, United States
Mason District Hospital
Havana, Illinois, United States
Illinois CancerCare - Kewanee Clinic
Kewanee, Illinois, United States
Illinois CancerCare - Macomb
Macomb, Illinois, United States
McDonough District Hospital
Macomb, Illinois, United States
Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
Moline, Illinois, United States
Moline, Illinois, United States
Illinois CancerCare - Monmouth
Monmouth, Illinois, United States
OSF Holy Family Medical Center
Monmouth, Illinois, United States
BroMenn Regional Medical Center
Normal, Illinois, United States
Community Cancer Center
Normal, Illinois, United States
Illinois CancerCare - 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 Treatment Center at Pekin Hospital
Pekin, Illinois, United States
Illinois CancerCare - Pekin
Pekin, Illinois, United States
Proctor Hospital
Peoria, Illinois, United States
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, United States
Methodist Medical Center of Illinois
Peoria, Illinois, United States
OSF St. Francis Medical Center
Peoria, Illinois, United States
Illinois CancerCare - Peru
Peru, Illinois, United States
Illinois Valley Community Hospital
Peru, Illinois, United States
Illinois CancerCare - Princeton
Princeton, Illinois, United States
Perry Memorial Hospital
Princeton, Illinois, United States
Illinois CancerCare - Spring Valley
Spring Valley, Illinois, United States
Bettendorf, Iowa, United States
Medical Oncology and Hematology Associates - West Des Moines
Clive, Iowa, United States
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates at Mercy Cancer Center
Des Moines, Iowa, United States
Mercy Cancer Center at Mercy Medical Center - Des Moines
Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Lutheran Hospital
Des Moines, Iowa, United States
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, United States
Mercy Medical Center - Sioux City
Sioux City, Iowa, United States
St. Luke's Regional Medical Center
Sioux City, Iowa, United States
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, United States
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, United States
Cancer Center of Kansas-Independence
Independence, Kansas, United States
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States
Lawrence Memorial Hospital
Lawrence, Kansas, United States
Cancer Center of Kansas, PA - Liberal
Liberal, Kansas, United States
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States
Associates in Womens Health, PA - North Review
Wichita, 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
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States
Saint Joseph Mercy Cancer Center
Ann Arbor, Michigan, United States
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, United States
Mecosta County Medical Center
Big Rapids, Michigan, United States
Oakwood Cancer Center at Oakwood Hospital and Medical Center
Dearborn, Michigan, United States
Green Bay Oncology, Limited - Escanaba
Escanaba, Michigan, United States
Genesys Hurley Cancer Institute
Flint, Michigan, United States
Hurley Medical Center
Flint, Michigan, United States
Butterworth Hospital at Spectrum Health
Grand Rapids, Michigan, United States
CCOP - Grand Rapids
Grand Rapids, Michigan, United States
Lacks Cancer Center at Saint Mary's Health Care
Grand Rapids, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States
Dickinson County Healthcare System
Iron Mountain, Michigan, United States
Foote Memorial Hospital
Jackson, Michigan, United States
Sparrow Regional Cancer Center
Lansing, Michigan, United States
St. Mary Mercy Hospital
Livonia, Michigan, United States
Mercy General Health Partners
Muskegon, Michigan, United States
St. Joseph Mercy Oakland
Pontiac, Michigan, United States
Mercy Regional Cancer Center at Mercy Hospital
Port Huron, Michigan, United States
Seton Cancer Institute at Saint Mary's - Saginaw
Saginaw, Michigan, United States
Munson Medical Center
Traverse City, Michigan, United States
St. John Macomb Hospital
Warren, Michigan, United States
Metro Health Hospital
Wyoming, Michigan, United States
MeritCare Bemidji
Bemidji, Minnesota, United States
Fairview Ridges Hospital
Burnsville, Minnesota, United States
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States
Duluth Clinic Cancer Center - Duluth
Duluth, Minnesota, United States
CCOP - Duluth
Duluth, Minnesota, United States
Miller - Dwan Medical Center
Duluth, Minnesota, United States
Fairview Southdale Hospital
Edina, Minnesota, United States
Fergus Falls Medical Group, PA
Fergus Falls, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States
Hutchinson Area Health Care
Hutchinson, Minnesota, United States
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, United States
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, United States
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, United States
United Hospital
Saint Paul, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, United States
Lakeview Hospital
Stillwater, Minnesota, United States
Ridgeview Medical Center
Waconia, Minnesota, United States
Willmar Cancer Center at Rice Memorial Hospital
Willmar, Minnesota, United States
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States
Goldschmidt Cancer Center
Jefferson City, Missouri, United States
Missouri Baptist Cancer Center
St Louis, Missouri, United States
Comprehensive Cancer Care, PC
St Louis, Missouri, United States
CCOP - Montana Cancer Consortium
Billings, Montana, United States
St. Vincent Healthcare Cancer Care Services
Billings, Montana, United States
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States
Billings Clinic - Downtown
Billings, Montana, United States
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States
St. James Healthcare Cancer Care
Butte, Montana, United States
Great Falls Clinic - Main Facility
Great Falls, Montana, United States
Sletten Cancer Institute at Benefis Healthcare
Great Falls, Montana, United States
Northern Montana Hospital
Havre, Montana, United States
St. Peter's Hospital
Helena, Montana, United States
Glacier Oncology, PLLC
Kalispell, Montana, United States
Kalispell Medical Oncology at KRMC
Kalispell, Montana, United States
Kalispell Regional Medical Center
Kalispell, Montana, United States
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States
Bismarck Cancer Center
Bismarck, North Dakota, United States
Medcenter One Hospital Cancer Care Center
Bismarck, North Dakota, United States
Mid Dakota Clinic, PC
Bismarck, North Dakota, United States
St. Alexius Medical Center Cancer Center
Bismarck, North Dakota, United States
CCOP - MeritCare Hospital
Fargo, North Dakota, United States
MeritCare Broadway
Fargo, North Dakota, United States
Natalie Warren Bryant Cancer Center at St. Francis Hospital
Tulsa, Oklahoma, United States
Geisinger Cancer Institute at Geisinger Health
Danville, Pennsylvania, United States
Geisinger Hazleton Cancer Center
Hazleton, Pennsylvania, United States
Geisinger Medical Group - Scenery Park
State College, Pennsylvania, United States
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, United States
Rapid City Regional Hospital
Rapid City, 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
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States
Green Bay Oncology, Limited at St. Mary's Hospital
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
Holy Family Memorial Medical Center Cancer Care Center
Manitowoc, Wisconsin, United States
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, United States
Green Bay Oncology, Limited - Oconto Falls
Oconto Falls, Wisconsin, United States
St. Nicholas Hospital
Sheboygan, Wisconsin, United States
Green Bay Oncology, Limited - Sturgeon Bay
Sturgeon Bay, Wisconsin, United States
Rocky Mountain Oncology
Casper, Wyoming, United States
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, United States
Countries
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References
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Hubbard JM, Mahoney MR, Loui WS, Roberts LR, Smyrk TC, Gatalica Z, Borad M, Kumar S, Alberts SR. Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma: North Central Cancer Treatment Group Trial N0745 (Alliance). Target Oncol. 2017 Apr;12(2):201-209. doi: 10.1007/s11523-016-0467-0.
Other Identifiers
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NCI-2009-01178
Identifier Type: REGISTRY
Identifier Source: secondary_id
CDR0000637866
Identifier Type: REGISTRY
Identifier Source: secondary_id
NCCTG-N0745
Identifier Type: -
Identifier Source: org_study_id
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