This randomized phase III trial studies sorafenib tosylate and doxorubicin hydrochloride to see how well they work compared with sorafenib tosylate alone in treating patients with liver cancer that has spread to nearby tissue or lymph nodes or has spread to other places in the body. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving sorafenib tosylate together with doxorubicin hydrochloride is more effective than sorafenib tosylate alone in treating liver cancer.
PRIMARY OBJECTIVES: I. Compare the overall survival (OS) of patients treated with sorafenib (sorafenib tosylate) and doxorubicin (doxorubicin hydrochloride) to that of those treated with sorafenib. SECONDARY OBJECTIVES: I. Compare time to progression (TTP) of patients treated with sorafenib and doxorubicin to that of those treated with sorafenib. II. Compare progression-free-survival (PFS) of patients treated with sorafenib and doxorubicin to that of those treated with sorafenib. III. Compare tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria of patients treated with sorafenib and doxorubicin to that of those treated with sorafenib. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive doxorubicin hydrochloride intravenously (IV) on day 1 and sorafenib tosylate orally (PO) once daily (QD) or twice daily (BID) on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may continue to receive sorafenib tosylate PO QD or BID in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive sorafenib tosylate PO QD or BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
356
Given IV
Correlative studies
Correlative studies
Given PO
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Providence Hospital
Mobile, Alabama, United States
Southern Cancer Center PC-Providence
Mobile, Alabama, United States
Alaska Regional Hospital
Anchorage, Alaska, United States
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
Overall Survival
Overall survival is defined as the time from study entry to death from any cause. The median OS was estimated using the Kaplan-Meier method.
Time frame: Up to 3 years
Incidence of Toxicities, as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The percentage of patients with a maximum grade 3 or higher adverse event at least possibly related to the study treatment are reported below.
Time frame: Up to 3 years
Progression Free Survival
Progression free survival is defined as the time from study entry to earliest date of disease progression. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression).
Time frame: Up to 3 years
Time to Progression (TTP)
Time to Progression (TTP) is defined as the time from on study to progression. Progression is defined by the RECIST criteria as Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression). Median and 95% confidence intervals are provided for each arm below.
Time frame: Up to 3 years
Best Overall Response Rate
Best Overall Response Rate is defined as is the best response recorded from the start of the treatment until disease progression/recurrence. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study.
Time frame: Up to 3 years
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