Sorafenib Tosylate with or without Stereotactic Body Radiation Therapy in Treating Patients with Liver Cancer

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Status: Active

Description

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, uses focused, high-dose radiation to help shrink tumors. It is not yet known whether giving sorafenib tosylate together with stereotactic body radiation therapy is more effective than sorafenib tosylate alone in treating liver cancer.

Eligibility Criteria

Inclusion Criteria

  • Patients must have an HCC diagnosis (initial, recurrent, progressive and/or refractory to other therapies) by at least one criterion listed below =< 360 days prior to study entry * Pathologically (histologically or cytologically) proven diagnosis of HCC * 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)
  • Patients must have 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 PRIOR TO STUDY ENTRY
  • 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): Within 28 days prior to study entry, CT scan chest/abdomen/pelvis or positron emission tomography (PET) CT chest/abdomen/pelvis with multiphasic liver CT or multiphasic liver magnetic resonance (MR) scan (MRI of abdomen and pelvis with contrast with CT chest) is permitted
  • Zubrod performance status 0-2 within 28 days prior to study entry
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3; obtained within 14 days prior to study entry
  • Platelets >= 60,000 cells/mm^3; obtained within 14 days prior to study entry
  • Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable); obtained within 14 days prior to study entry
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 6 times upper limit of normal (ULN); obtained within 14 days prior to study entry
  • Serum creatinine =< 1.2 x ULN or creatinine clearance >= 60 mL/min; obtained within 14 days prior to study entry
  • Patients must have Barcelona Clinic Liver Cancer (BCLC) stage: intermediate (B) or advanced (C) within 28 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 and T1 renal cell carcinoma) 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 and/or grade 3 or 4 sorafenib related toxicity; note that prior chemotherapy for HCC or a different cancer is allowable
  • Prior radiotherapy to the region of the liver that would result in excessive doses to normal tissues due to 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 PRIOR TO 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 28 days prior to study entry * Bleeding within 28 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
  • Maximal diameter of any one hepatocellular carcinoma > 15 cm
  • Total sum of maximum diameters of each definite parenchymal hepatocellular carcinomas within the liver or maximum diameter of a single conglomerate HCC > 20 cm
  • More than 5 discrete intrahepatic parenchymal foci of definite 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
  • Prior liver transplant
  • Human immunodeficiency virus (HIV) positive with CD4 count < (350) cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= (350) cells/microliter, and no known detectable viral load, at the time of study entry; note also that HIV testing is not required for eligibility for this protocol

Locations & Contacts

California

Berkeley
Alta Bates Summit Medical Center-Herrick Campus
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
Los Angeles
USC / Norris Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 323-865-0451

Colorado

Aurora
University of Colorado Hospital
Status: Active
Contact: Site Public Contact
Phone: 720-848-0650

Connecticut

Bridgeport
Saint Vincent's Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-823-5923
Email: ctsucontact@westat.com

Hawaii

Honolulu
Queen's Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 412-339-5294
Email: Roster@nrgoncology.org

Illinois

Chicago
University of Illinois
Status: Active
Contact: Site Public Contact
Phone: 312-355-3046
Decatur
Decatur Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 217-876-4740
Email: rhamrick@dmhhs.org
Maywood
Loyola University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 708-226-4357
Warrenville
Northwestern Medicine Cancer Center Warrenville
Status: Active
Contact: Site Public Contact
Phone: 630-315-1918
Email: Claudine.Gamster@CadenceHealth.org

Iowa

Des Moines
Iowa Methodist Medical Center
Status: Active
Contact: Site Public Contact
Phone: 515-241-6727

Louisiana

New Orleans
Ochsner Medical Center Jefferson
Status: Active
Contact: Site Public Contact
Phone: 504-703-8712
Email: Gregory.Johnstone@ochsner.org

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 410-955-8804
Email: jhcccro@jhmi.edu

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-726-5130

Minnesota

Minneapolis
Minneapolis Veterans Medical Center
Status: Active
Contact: Site Public Contact
Phone: 612-467-2800

Missouri

Saint Louis
Missouri Baptist Medical Center
Status: Active
Contact: Site Public Contact
Phone: 314-996-5569

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Site Public Contact
Phone: 718-379-6866
Email: aaraiza@montefiore.org
New York
Memorial Sloan Kettering Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 212-639-7592
Rochester
University of Rochester
Status: Active
Contact: Site Public Contact
Phone: 585-275-5830
Stony Brook
Stony Brook University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-862-2215

Ohio

Cleveland
Case Western Reserve University
Status: Active
Contact: Site Public Contact
Phone: 800-641-2422
Email: CTUReferral@UHhospitals.org
Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-293-5066
Email: Jamesline@osumc.edu

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-474-9892

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-312-3961

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Site Public Contact
Phone: 888-424-2100
Email: cancerinfo@hci.utah.edu

Virginia

Richmond
Hunter Holmes McGuire Veterans Administration Medical Center
Status: Active
Contact: Site Public Contact
Phone: 804-675-5646
Email: Regina.McClung@va.gov

Washington

Seattle
ProCure Proton Therapy Center-Seattle
Status: Active
Contact: Site Public Contact
Phone: 412-339-5294
Email: Roster@nrgoncology.org
University of Washington Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-804-8824

Alberta

Calgary
Tom Baker Cancer Centre
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 403-521-3433

Ontario

Hamilton
Juravinski Cancer Centre at Hamilton Health Sciences
Status: Active
Contact: Site Public Contact
Phone: 905-387-9495
London
London Regional Cancer Program
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 519-685-8600
Toronto
University Health Network-Princess Margaret Hospital
Status: Active
Contact: Site Public Contact
Phone: 416-946-4501
Email: clinical.trials@uhn.on.ca

Quebec

Montreal
CHUM - Centre Hospitalier de l'Universite de Montreal
Status: Active
Contact: Site Public Contact
Phone: 412-339-5294
Email: Roster@nrgoncology.org
CHUM - Hopital Notre-Dame
Status: Active
Contact: Guila Delouya
Phone: 514-890-8000ext23611
Email: sylvie.beaudoin.chum@ssss.gouv.qc.ca
The Research Institute of the McGill University Health Centre (MUHC)
Status: Active
Contact: Site Public Contact
Phone: 514-934-1934ext48354
Email: evelyn.ortega@muhc.mcgill.ca

Australia

Melbourne
Peter MacCallum Cancer Centre
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 61 3 9656 1521

Korea, Republic of

Seoul
Samsung Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 011-82-1599-3114

Trial Objectives and Outline

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 I: 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 II: 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 as in Arm I. Treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
NRG Oncology

Principal Investigator
Laura Ann Dawson

Trial IDs

Primary ID RTOG-1112
Secondary IDs NCI-2012-02057
Clinicaltrials.gov ID NCT01730937