Sorafenib Tosylate With or Without Stereotactic Body Radiation Therapy in Treating Patients With Liver Cancer

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentActive18 and overNCI, OtherRTOG 1112
NCI-2012-02057, U10CA021661, NCT01730937

Trial Description

Summary

This randomized phase III trial studies sorafenib tosylate and stereotactic body radiation therapy to see how well they work compared to sorafenib tosylate alone in treating patients with liver cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Stereotactic body radiation therapy may be able to send the radiation dose directly to the tumor and cause less damage to normal tissue. Giving sorafenib tosylate together with stereotactic body radiation therapy may kill more tumor cells.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine if stereotactic body radiation therapy (SBRT) improves overall survival in hepatocellular carcinoma (HCC) patients treated with sorafenib (sorafenib tosylate).

SECONDARY OBJECTIVES:

I. To determine the difference in time to progression (TTP) and progression-free survival (PFS) in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.

II. To measure differences in toxicity in HCC patients treated with sorafenib versus SBRT followed by sorafenib.

III. To measure vascular thrombosis response post sorafenib versus SBRT followed by sorafenib.

IV. To measure differences in health related quality of life (QOL) and quality-adjusted survival in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.

V. Collection of biospecimens for future correlative studies to investigate differences in potential biomarkers in patients treated with sorafenib versus SBRT followed by sorafenib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM 1: Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients undergo SBRT every 24-72 hours for a total of 5 fractions over 5 to 15 days. Within 1-5 days post-SBRT, patients receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

Patients are followed weekly during SBRT, monthly during sorafenib tosylate and on the following schedule as a whole from study entry: every 3 months for 3 years, then every 6 months for 2 years and then annually.

Eligibility Criteria

Inclusion Criteria:

  • Patients must have a diagnosis of HCC by at least one criterion listed below within 360 days prior to study entry:
  • Pathologically (histologically or cytologically) proven diagnosis of HCC,(biopsies are recommended, and are to be submitted for research evaluation if patients consent)
  • At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, inferior vena cava [IVC] and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multi-phasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis.
  • For patients whose CURRENT disease is vascular only: enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI in a patient with known HCC (diagnosed previously <720 days) using the above criteria.
  • Measureable hepatic disease and/or presence of vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) which may not be measureable as per Response Evaluation Criteria in Solid Tumors (RECIST) on liver CT or MRI, within 28 days of registration
  • Appropriate for protocol entry based upon the following minimum diagnostic workup:
  • History/physical examination including examination for encephalopathy, ascites, weight, height, and blood pressure within 14 days prior to study entry
  • Assessment by radiation oncologist and medical oncologist or hepatologist who specializes in treatment of HCC within 28 days prior to study entry
  • Pre-randomization Scan (REQUIRED for All Patients): CT scan chest/abdomen/pelvis with multiphasic liver CT scan or multiphasic liver MR scan within 28 days prior to study entry. MRI of abdomen with contrast and pelvis is permitted.
  • Zubrod performance status 0-2 within 28 days prior to study entry
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Platelets >= 70,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  • Total bilirubin < 2 mg/dL
  • Internationalized Normalized Ratio (INR) < 1.7
  • Albumin >= 28 g/L
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 6 times upper limit of normal (ULN)
  • Serum creatinine =< 1.5 x ULN or creatinine clearance >= 60 mL/min
  • Barcelona Clinic Liver Cancer (BCLC) stage: intermediate (B) or advanced (C) within 14 days prior to study entry
  • Child-Pugh score A within 14 days prior to study entry
  • Women of childbearing potential and male participants must agree to practice adequate contraception while on study and for at least 6 months following the last dose of radiation therapy (RT) and for at least 28 days following the last dose of sorafenib (whichever is later)
  • Unsuitable for resection or transplant or radiofrequency ablation (RFA)
  • Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) or drug eluting beads (DEB) for any of the following reasons, as described by Raoul et al (2011):
  • Technical contraindications: arteriovenous fistula, including, surgical portosystemic shunt or spontaneous portosystemic shunt
  • Severe reduction in portal vein flow: due to tumor portal vein, IVC or atrial invasion or bland portal vein occlusion
  • Medical contraindications including congestive heart failure, angina, severe peripheral vascular disease
  • Presence of extrahepatic disease
  • No response post TACE (or DEB) or progressive HCC despite TACE; prior TACE or DEB is allowed but must be > 28 days from study entry
  • Serious toxicity following prior TACE (or DEB); prior TACE or DEB must be > 28 days from study entry
  • Other medical comorbidities making TACE (or DEB) unsafe and/or risky (e.g. combination of relative contraindications including age > 80 years, tumor > 10 cm, > 50% replacement of the liver by HCC, extensive multinodular bilobar HCC, biliary drainage)
  • Patients treated with prior surgery are eligible for this study if they otherwise meet eligibility criteria
  • Patient must be able to provide study-specific informed consent prior to study entry

Exclusion Criteria:

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior sorafenib use > 60 days. Note that prior chemotherapy for HCC or a different cancer is allowable
  • Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
  • Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
  • Severe, active co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months before registration
  • Transmural myocardial infarction within the last 6 months prior to study entry
  • Unstable ventricular arrhythmia within the last 6 months prior to study entry
  • Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry
  • Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 60 days prior to study entry
  • Bleeding within 60 days prior to study entry due to any cause, requiring transfusion
  • Thrombolytic therapy within 28 days prior to study entry. Subcutaneous heparin is permitted.
  • Known bleeding or clotting disorder
  • Uncontrolled psychotic disorder
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • Any one hepatocellular carcinoma > 15 cm
  • Total maximal sum of hepatocellular carcinomas or a single conglomerate HCC > 20 cm
  • More than 5 discrete intrahepatic parenchymal foci of HCC
  • Direct tumor extension into the stomach, duodenum, small bowel or large bowel
  • Measureable common or main branch biliary duct involvement with HCC
  • Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
  • Use of regular phenytoin, carbamazepine, hypericum perforatum (also known as St. John's wort) or rifampin
  • Use of combination anti-retroviral therapy for human immunodeficiency virus (HIV), as these agents may modulate cytochrome P450 isozymes
  • Prior liver transplant

Trial Contact Information

Trial Lead Organizations/Sponsors

Radiation Therapy Oncology Group

  • National Cancer Institute
Laura A. Dawson, Principal Investigator

Trial Sites

U.S.A.

California
Los Angeles

USC/Norris Comprehensive Cancer Center and Hospital

Anthony Boutros El-Khoueiry
Ph: 323-865-0451

Connecticut
Bridgeport

St. Vincent's Medical Center

Christopher M Iannuzzi
Ph: 203-576-6329
Email: twhite@stvincents.org

Illinois
Chicago

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

John P Hayes
Ph: 312-695-1301
Email: cancer@northwestern.edu

University of Illinois Cancer Center

Neeta K Venepalli
Ph: 312-355-3046

Maryland
Baltimore

Greenebaum Cancer Center at University of Maryland Medical Center

Michael D Chuong
Ph: 800-888-8823

Massachusetts
Boston

Boston University Cancer Research Center

Lisa A. Kachnic
Ph: 617-638-8265

Massachusetts General Hospital

Andrew X. Zhu
Ph: 877-726-5130

Michigan
Ann Arbor

University of Michigan Comprehensive Cancer Center

Mary U Feng
Ph: 800-865-1125

Missouri
Saint Louis

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

Jeffrey R Olsen
Ph: 800-600-3606
Email: info@siteman.wustl.edu

New York
Bronx

Montefiore Medical Center

Nitin Ohri
Ph: 718-904-2730
Email: aecc@aecom.yu.edu

New York

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

Abby Siegel
Ph: 212-305-8615

Rochester

James P. Wilmot Cancer Center at University of Rochester Medical Center

Yuhchyau Chen
Ph: 585-275-5830

Ohio
Columbus

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Terence M Williams
Ph: 800-293-5066
Email: Jamesline@osumc.edu

Texas
Houston

Univeristy of Texas M.D. Anderson Cancer Center

Sunil Krishnan
Ph: 713-792-3245

Virginia
Richmond

Veterans Affairs Medical Center - Richmond

Drew Moghanaki
Ph: 804-628-1939

Wisconsin
Milwaukee

Froedtert Hospital and Medical College of Wisconsin

Beth Ann Erickson
Ph: 414-805-4380

Canada

Ontario
Hamilton

Margaret and Charles Juravinski Cancer Centre

Anand Swaminath
Ph: 905-387-9495

London

London Regional Cancer Program at London Health Sciences Centre

Michael I Lock
Ph: 519-685-8600

Toronto

Princess Margaret Hospital

Laura A Dawson
Ph: 416-946-4501
Email: clinical.trials@uhn.on.ca

Quebec
Montreal

Hopital Notre-Dame du CHUM

Helene Castel
Ph: 514-890-8000ext12725
Email: info.cr.chum@ssss.gouv.qc.ca

Hong Kong

Chai Wan

Pamela Youde Nethersole Eastern Hospital

Ada L Law
Ph: 888-823-5923
Email: ctsucontact@westat.com

Republic of Korea

KOREA
Seoul

Samsung Medical Center

Hee Chul Park
Ph: 011-82-1599-3114

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01730937
ClinicalTrials.gov processed this data on February 27, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.