Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

Tracking Information
First Submitted Date ICMJE	November 17, 2009
First Posted Date ICMJE	November 18, 2009
Last Update Posted Date	August 23, 2017
Actual Study Start Date ICMJE	February 15, 2010
Actual Primary Completion Date	May 21, 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 19, 2012)	Overall survival [ Time Frame: Up to 3 years ]; The confidence bound estimates for futility will also be adjusted according to the Lan-DeMets analogue of the O'Brien-Fleming boundaries.
Original Primary Outcome Measures ICMJE; (submitted: November 17, 2009)	Overall survival
Change History	Complete list of historical versions of study NCT01015833 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 17, 2014)	Incidence of adverse events, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 years ]Incidence of other adverse events (proteinuria, hypertension, and other common side effects of study drugs) will be assessed.; Progression free survival [ Time Frame: Up to 3 years ]The stratified log-rank test will be used.
Original Secondary Outcome Measures ICMJE; (submitted: November 17, 2009)	Toxicity as assessed by NCI CTC v3.0; Time to progression; Progression free survival
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer
Official Title ICMJE	Phase III Randomized Study of Sorafenib Plus Doxorubicin Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
Brief Summary	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.
Detailed Description	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 ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Investigator); Primary Purpose: Treatment
Condition ICMJE	Advanced Adult Hepatocellular Carcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7
Intervention ICMJE	Drug: Doxorubicin Hydrochloride Given IV; Other: Laboratory Biomarker Analysis Correlative studies; Other: Pharmacogenomic Study Correlative studies; Drug: Sorafenib Tosylate Given PO
Study Arms	Experimental: Arm I (doxorubicin hydrochloride, sorafenib tosylate) Patients receive doxorubicin hydrochloride IV on day 1 and sorafenib tosylate PO QD or 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. Interventions: Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacogenomic Study Drug: Sorafenib Tosylate; Experimental: Arm II (sorafenib tosylate) 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. Interventions: Other: Laboratory Biomarker Analysis Other: Pharmacogenomic Study Drug: Sorafenib Tosylate
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: August 21, 2017)	360
Original Estimated Enrollment ICMJE; (submitted: November 17, 2009)	480
Study Completion Date	Not Provided
Actual Primary Completion Date	May 21, 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patients must have pathologically or cytologically proven hepatocellular carcinoma; known mixed histology (e.g. hepatocellular carcinoma plus cholangiocarcinoma) or fibrolamellar variant is not allowed; Patients must have locally advanced or metastatic disease; locally advanced disease is defined as disease deemed to be unresectable or non-eligible for transplant without distant metastases; Lesions must be accurately measurable in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan; No prior adjuvant sorafenib or other v-RAF-1 murine leukemia viral oncogene homolog (Raf)/vascular endothelial growth factor (VEGF) inhibitors; other prior adjuvant therapy is allowed if completed > 6 months prior to registration with documented recurrence of hepatocellular carcinoma (HCC); Patients may have been treated with loco regional therapies provided that they either have: A target lesion that has not been subjected to local therapy or The target lesion(s) within the field of the local therapy has shown an increase of >= 20% in the size since last treatment Such therapy must be completed at least 4 weeks prior to registration; patients that have received palliative radiation therapy to the bone need not wait 4 weeks to begin protocol therapy; Prior therapies allowed include the following: Bland embolization, radiation, radioactive microspheres, etc Chemoembolization using any chemotherapy (except, see below) Chemoembolization drug-eluting beads using doxorubicin Prior therapy with chemoembolization using doxorubicin in the non drug eluting beads form is NOT allowed; No prior systemic therapy for metastatic disease; No prior exposure to systemic doxorubicin administered intravenously; Antiviral treatment is allowed, however interferon therapy must be stopped at least 4 weeks prior to registration; Allografts are not allowed: no prior history of any allograft, including but not limited to liver and bone marrow transplants; Patients must have completed any major surgery >= 4 weeks from registration; Concomitant treatment with Rifampin or St John's wort is not allowed; patients should discontinue these drugs at least 4 weeks prior to registration; No known central nervous system (CNS) tumors including brain metastases; No clinically significant gastrointestinal bleeding events requiring intervention, transfusion, or admission to hospital within 30 days prior to registration; Patients with a history of hypertension should be well controlled (< 140/90 mmHg) on a regimen of anti-hypertensive therapy; Significant history of cardiac disease is not allowed: Congestive heart failure > class II New York Heart Association (NYHA) Myocardial infarction within 6 months prior to registration Serious myocardial dysfunction, defined as scintigraphically (multigated acquisition scan [MUGA], myocardial scintigram) determined absolute left ventricular ejection fraction (LVEF) below 45% or an LVEF on echocardiogram (ECHO) below the normal limit at the individual institution; No history of bleeding diathesis; Patients receiving combination anti-retroviral therapy for human immunodeficiency virus (HIV) are excluded from the study; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Pregnancy/nursing status: women who are pregnant should not go on study; women should not breastfeed while participating in this study; Granulocytes >= 1,500/uL; Hemoglobin >= 8.5 g/dL; patients with recent or ongoing gastrointestinal bleed may not be transfused to reach the entry hemoglobin of 8.5 g/dL; physicians should ensure patients requiring transfusion prior to registration do not have an occult or clinically apparent gastrointestinal bleed; Platelets >= 75,000/uL; Creatinine =< 1.5 x upper limit of normal (ULN) (or creatinine clearance calculated >= 60 cc/minute); Child-Pugh score A; patients must meet all laboratory value requirements; Bilirubin =< 3 mg/dL; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x ULN; Prothrombin time (PT)-international normalized ratio (INR) =< 1.7 (not required for patients on anticoagulation agents; patients who are being therapeutically anticoagulated with an agent such as Coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada, Puerto Rico, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01015833
Other Study ID Numbers ICMJE	NCI-2011-01989; NCI-2011-01989 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000659348; CALGB-80802 ( Other Identifier: Alliance for Clinical Trials in Oncology ); CALGB-80802 ( Other Identifier: CTEP ); U10CA180821 ( U.S. NIH Grant/Contract ); U10CA031946 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Cancer Institute (NCI)
Study Sponsor ICMJE	National Cancer Institute (NCI)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Ghassan Abou-Alfa Alliance for Clinical Trials in Oncology
PRS Account	National Cancer Institute (NCI)
Verification Date	August 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP