Sorafenib Tosylate With or Without Stereotactic Body Radiation Therapy in Treating Patients With Liver Cancer
Randomized Phase III Study of Sorafenib Versus Stereotactic Body Radiation Therapy Followed by Sorafenib in Hepatocellular Carcinoma
3 other identifiers
interventional
193
5 countries
51
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Apr 2013
Longer than P75 for phase_3
51 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
November 15, 2012
CompletedFirst Posted
Study publicly available on registry
November 21, 2012
CompletedStudy Start
First participant enrolled
April 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2022
CompletedResults Posted
Study results publicly available
July 3, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
September 4, 2025
CompletedJanuary 28, 2026
September 1, 2025
9.3 years
November 15, 2012
May 24, 2023
January 8, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Survival
An event for overall survival (OS) is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 153 deaths were reported.
From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
Secondary Outcomes (6)
Time to Progression
From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
Progression-free Survival
From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
Number of Participants by Highest Grade Adverse Event Reported
From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
Percentage of Participants With Improvement in the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Total Score 6 Months After the Start of Treatment
Baseline and 6 months
Best Vascular Thrombosis Response up to the Time of Progressive Disease (if Applicable)
From randomization to last follow-up. Imaging occurs every 3 months for two years then every six months. Maximum follow-up at time of analysis was 7.6 years.
- +1 more secondary outcomes
Other Outcomes (3)
Overall Survival by Sex
From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
Overall Survival by Ethnicity
From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
Overall Survival by Race
From randomization to last follow-up: weekly during SBRT, post-SBRT/pre-sorafenib, monthly during sorafenib, and overall, from study entry: every 3 months for 2 years, then every 6 months. Maximum follow-up at time of analysis was 7.6 years.
Study Arms (2)
Sorafenib Alone
ACTIVE COMPARATOR400 mg sorafenib twice a day for 28-day cycle. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.
SBRT followed by Sorafenib
EXPERIMENTAL27.5 Gy to 50 Gy stereotactic body radiation therapy (SBRT) in 5 fractions 24-72 hours apart over 5-15 days followed within 1-5 days by one cycle of 200 mg sorafenib twice a day. Starting with second cycle, if tolerable, increase to 400 mg sorafenib twice a day. Continue up to 5 years in the absence of disease progression or unacceptable toxicity.
Interventions
By mouth (PO)
Intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and proton therapy are allowed.
Eligibility Criteria
You may qualify if:
- 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): Within 28 days prior to study entry, multiphasic liver CT or multiphasic liver MR scan.
- Within 28 days prior to study entry CT chest with CT or MR abdomen and CT or MR pelvis, or positron emission tomography (PET) CT chest/abdomen/pelvis.
- Zubrod performance status 0-2 within 28 days prior to study entry
- All blood work obtained within 14 days prior to study entry with adequate organ marrow function defined as follows:
- Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3
- Platelets \>= 60,000 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)
- +16 more criteria
You may not qualify if:
- 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 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
- Maximal diameter of any one hepatocellular carcinoma \> 15 cm
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Radiation Therapy Oncology Grouplead
- National Cancer Institute (NCI)collaborator
- NRG Oncologycollaborator
Study Sites (51)
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
University of Colorado Hospital
Aurora, Colorado, 80045, United States
Saint Vincent's Medical Center
Bridgeport, Connecticut, 06606, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Columbia University/Herbert Irving Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
Hunter Holmes McGuire Veterans Administration Medical Center
Richmond, Virginia, 23249, United States
ProCure Proton Therapy Center-Seattle
Seattle, Washington, 98133, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2, Canada
London Regional Cancer Program
London, Ontario, N6A 4L6, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
CHUM - Hopital Notre-Dame
Montreal, Quebec, H2L 4M1, Canada
CHUM - Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, H2X 3E4, Canada
The Research Institute of the McGill University Health Centre (MUHC)
Montreal, Quebec, H3H 2R9, Canada
Pamela Youde Nethersole Eastern Hospital
Chai Wan, Hong Kong
Samsung Medical Center
Seoul, Korea, 135-710, South Korea
Related Publications (1)
Dawson LA, Winter KA, Knox JJ, Zhu AX, Krishnan S, Guha C, Kachnic LA, Gillin MT, Hong TS, Craig TD, Williams TM, Hosni A, Chen E, Noonan AM, Koay EJ, Sinha R, Lock MI, Ohri N, Dorth JA, Delouya G, Swaminath A, Moughan J, Crane CH. Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2025 Feb 1;11(2):136-144. doi: 10.1001/jamaoncol.2024.5403.
PMID: 39699905DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The trial closed to accrual in March 2021 at 193 of 292 planned patients due to a change in the systemic standard of care for this disease, from sorafenib to atezolizumab and bevacizumab. As the original number of OS events (238) couldn't be met, the statistical analysis plan (SAP) was revised to report the study using available patients, with data through 7/1/2022. The changes were done by a statistician independent from the trial in accordance with the NCI Policy for Major Design Amendments.
Results Point of Contact
- Title
- Wendy Seiferheld
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
Laura Dawson
Radiation Therapy Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 15, 2012
First Posted
November 21, 2012
Study Start
April 1, 2013
Primary Completion
July 1, 2022
Study Completion
September 4, 2025
Last Updated
January 28, 2026
Results First Posted
July 3, 2023
Record last verified: 2025-09