Study of Sorafenib and Transarterial Chemoembolization (TACE) to Treat Hepatocellular Carcinoma

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00844883
• Collaborator: Bayer (Industry), Biocompatibles UK Ltd (Industry)
• Enrollment: 50
• Location: 1
• Arm: 1
• Duration (Months): 72.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will combine two therapies to treat patients with unresectable hepatocellular carcinoma; sorafenib, and drug eluting beads delivered intra-arterially. The purpose of the study is to establish the safety and the effectiveness of the combination therapy. The investigators hypothesize that the combination of the two therapies will not result in greater toxicities to patients than that expected for either therapy given alone.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma; Hepatoma	Drug: sorafenib; Procedure: LC Bead-TACE	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Sorafenib Combined With Doxorubicin Eluting Bead-Transarterial Chemoembolization (LC Bead-TACE) for Patients With Hepatocellular Carcinoma
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: sorafenib and drug eluting beads single arm	Drug: sorafenib; sorafenib: given 400 mg twice per day for as long as it is beneficial; Other Names: sorafenib (Nexavar) ; Procedure: LC Bead-TACE; LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period; Other Names: LC Beads manufactured by Biocompatibles

Outcome Measures

Primary Outcome Measures

1. Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment. [6 weeks (Cycle 1)]

   Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more. 50 patients were reviewed for toxicities for Cycle 1, and all 50 patients experienced at least one adverse event during this time period.

2. Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment. [2 years (Cycles 2-5+)]

   Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more.

Secondary Outcome Measures

1. Efficacy Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) to Determine Response and Disease Control Rate [6 months]

   Efficacy as assessed by radiographic tumor response using the RECIST criteria at baseline and at 6 months post the initiation of treatment. 33 out of the original 50 patients were evaluable at this time point, with 17 out of the 50 exiting prior to 6 months or were not assessable by RECIST criteria. Complete response (CR): Disappearance of all lesions targeted with therapy Partial Response (PR): at least 30% decrease in sum of longest diameter (LD) of targeted lesions Progressive Disease (PD): at least 20% increase in the sum of LD of targeted lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD

2. Efficacy Assessed by European Association for the Study of the Liver (EASL) Criteria to Determine Response and Disease Control Rate [6 months]

   Efficacy as assessed by radiographic tumor response using the EASL criteria at baseline and at 6 months post the initiation of treatment. Complete response (CR): 100% tumor necrosis Partial Response (PR): more than 50% tumor necrosis Progressive Disease (PD): increase in tumor enhancement by more than 25% Stable Disease (SD): Cases that do not qualify for one of the above criteria

3. Efficacy - Median TTP After Combination Treatment With Sorafenib and TACE [3 years]

   Time to progression (TTP) - defined as the time from initiation of therapy to disease progression (radiological). Median TTP calculated for all subjects and stratified by Barcelona Clinic Liver Cancer (BCLC) staging. 46 patients out of 50 were reviewed for this outcome. 3 patients were excluded because they underwent liver transplantation and 1 patient was excluded for hepatic resection.

4. Efficacy - Overall Survival (OS) After Combination Treatment With Sorafenib and TACE [3 years]

   Overall survival was assessed with Kaplan-Meier estimates of survival, and the Mantel-Cox log-rank test was used to determine differences in survival. All 50 patients were included in survival analyses as all 50 received at least one dose of sorafenib.

5. Efficacy - Factors Associated With Overall Survival (OS) After Combination Treatment With Sorafenib and TACE [3 years]

   Overall survival was assessed with Kaplan-Meier estimates of survival, and the Mantel-Cox log-rank test was used to determine differences in survival.

Other Outcome Measures

1. Estimated Percentage of Participants Surviving After One Year [1 year]

   Percentage of study patients surviving after one year from initial treatment analyzed with Kaplan-Meier curve.

2. Estimated Percentage of Participants Surviving After Three Year [3 years]

   Percentage of study patients surviving after three years from initial treatment analyzed with Kaplan-Meier curve.

3. Median Overall Survival OS Stratified by BCLC Criteria [up to 4 years]

   Median overall survival stratified by Barcelona Clinic Liver Cancer (BCLC) staging as assessed by Kaplan-Meier estimator. Patients are grouped to stages A (early), B (intermediate), and C (advanced) according to stage of disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Unresectable hepatocellular carcinoma (HCC) patients with liver-predominant disease as described in section 5.1, or patients with hepatocellular carcinoma who refuse surgery. No more than 30% of the cohort should have macrovascular invasion and/or asymptomatic extrahepatic disease. Multifocal HCC is acceptable, no diffuse HCC.

2. Age > 18 years old

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

4. Childs class of A or B (up to 7) (see Table 5.0)

5. Adequate end-organ function as manifested by:

• Absolute neutrophil count of > 1500/mm3 and platelets > 50,000/mm3

• Creatinine ≤ 2.0

• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)

• Total bilirubin of ≤ 3

• Albumin > 2.0

• International normalized ratio (INR) < 2.0

• Leukocyte count >3000 cells/mm3

1. Amylase and lipase ≤ 1.5 the upper limit of normal

2. Patients who have received previous hepatic surgery , radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or cryoablation are eligible if target lesion(s) have not been treated and local therapy completed > 6 weeks prior to entry.

3. Left ventricular ejection fraction ≥ 45%

4. Patients with asymptomatic HIV infection are not eligible

5. Willingness of male and female subjects, who are not surgically sterile or post menopausal, to use reliable methods of birth control for the duration of the study and for 30 days after the last dose of study medication.

6. Patient must have signed informed consent prior to registration on study.

7. Resolution of all acute toxic effects of any prior local treatment to Common Terminology Criteria for Adverse Events (CTCEA) Grade 1 or 0.

8. At least one tumor lesion can be accurately measured in at least one dimension according to RECIST. The lesion has not been previously treated with local therapy (such as surgery, radiation therapy, RFA, PEI, or cryoablation) unless it has shown progression in the interim.

Exclusion Criteria:

1. Patients unable to swallow oral medications

2. Prior embolization, systemic or radiation therapy for HCC (liver)

3. Tumor burden in the liver exceeding 70%.

4. Complete occlusion of the entire portal venous system

5. Ascites refractory to diuretic therapy (minimal or trace on imaging is acceptable)

6. Previous or concurrent cancer that is distinct in primary site or histology from HCC, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1). Any cancer curatively treated > 3 years prior is permitted.

7. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry

8. History of bleeding within the past 4 weeks (unless deemed by PI as clinically insignificant, for ex., a brief episode of epistaxis)

9. Any contraindication to doxorubicin administration

10. Evidence of severe or uncontrolled systemic diseases,

11. Congestive cardiac failure > New York Heart Association (NYHA) class 2, myocardial ischemia within 6 months, active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, unstable angina, or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial

12. Any prior history of hypertensive crisis or hypertensive encephalopathy

13. History of stroke or transient ischemic attack within 6 months prior to study enrollment

14. Inadequately controlled hypertension (defined as systolic blood pressure of 150/100 mmHg on antihypertensive medications) (patients with treated hypertension are eligible)

15. Significant vascular disease (e.g., aortic aneurysm, aortic dissection, peripheral vascular disease)

16. History of organ allograft

17. Presence of grade > 2 hepatic encephalopathy (see Appendix D)

18. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an additional experimental drug

19. Evidence of bleeding diathesis or coagulopathy or on warfarin. Note: If a patient has been on coumadin for a period of 1 month and has been stable, they may be accepted into the protocol.

20. Presence of clinically evident central nervous system or brain metastases

21. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study

22. Vascular anatomy that precludes catheter placement or injection of LC Bead microspheres

23. Presence of collateral vessel pathways potentially endangering normal territories during embolization

24. Pregnant (positive pregnancy test) or lactating

25. Inability to comply with study and/or follow-up procedures

26. Life expectancy of less than 12 weeks

27. Child B8, B9 and C

28. ECOG ≥ 2

29. Patients with concomitant HIV infection or AIDS-related or serious acute or chronic illness

30. Presence of porto-systemic shunt

31. Severe atheromatosis

32. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results

33. Active clinically serious infections (>grade 2)

34. Patients receiving therapy for hepatitis A, B, or C.

35. Patients with obvious and/or symptomatic extrahepatic disease. Findings of uncertain significance, such as lung lesions less than 10 mm in diameter or enlarged periportal lymph nodes will not exclude patients, however, findings highly suspicious for metastatic HCC will exclude patients from this study.

36. Any contraindication for an arterial procedure such as impaired clotting tests (platelet count < 50.000/mm3 or prothrombin activity < 50 percent)

37. Any contraindication for systemic chemotherapy administration (serum bilirubin > 3mg/dL, leukocyte count < 3.000 cells/mm3)

38. Any contraindication for sorafenib administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Johns Hopkins Hospital	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Yale University
• Bayer
• Biocompatibles UK Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00844883
• Other Study ID Numbers: J08110
• First Posted: Feb 16, 2009
• Last Update Posted: Nov 11, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Yale University: primary liver cancer; sorafenib; Nexavar; doxorubicin; drug eluting beads; transarterial chemoembolization
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Sorafenib

Study Results

Participant Flow

Recruitment Details	This study enrolled patients diagnosed with unresectable hepatocellular carcinoma who were eligible to receive a combination therapy of sorafenib and transarterial chemoembolization. Enrollment took place from 3/2009 to 12/2011 at Johns Hopkins Hospital.
Pre-assignment Detail	90 patients consented and screened for study. 38 were ineligible and 2 later declined participation.

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Period Title: Overall Study
STARTED	50
Patients Who Received TACE	48
COMPLETED	46
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Overall Participants	50
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	12 24%
Male	38 76%
Region of Enrollment (Count of Participants)
United States	50 100%

Outcome Measures

1. Primary Outcome

Title	Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment.
Description	Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more. 50 patients were reviewed for toxicities for Cycle 1, and all 50 patients experienced at least one adverse event during this time period.
Time Frame	6 weeks (Cycle 1)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	50
Anemia	13 26%
Lymphopenia	24 48%
Thrombocytopenia	8 16%
Arrhythmia	4 8%
Chest pain	2 4%
Dissection	1 2%
Embolus or coagulopathy	1 2%
Hypertension	7 14%
Lower extremity edema	12 24%
Fatigue	42 84%
Fever	15 30%
Hand-foot skin reaction	23 46%
Mucositis	11 22%
Rash	26 52%
Skin pain	4 8%
Ascites	3 6%
Anorexia	28 56%
Diarrhea	19 38%
Nausea or vomiting	24 48%
Epistaxis or hemoptysis	1 2%
Hematochezia	2 4%
Hematoma	3 6%
Tumor rupture	1 2%
Elevated ALT level	25 50%
Elevated AST level	24 48%
Elevated AP level	17 34%
Elevated amylase level	10 20%
Elevated lipase level	15 30%
Elevated INR level	16 32%
Hyperbilirubinemia	30 60%
Hypoalbuminemia	27 54%
Infection	6 12%
Dizziness	4 8%
Headache	9 18%
Encephalopathy	3 6%
Nonspecific abdominal pain	24 48%
Musculoskeletal pain	24 48%
Right upper quadrant pain	24 48%
Pain - other	12 24%
Acute renal failure	3 6%
Death (disease progression)	1 2%

2. Primary Outcome

Title	Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment.
Description	Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more.
Time Frame	2 years (Cycles 2-5+)

Outcome Measure Data

Analysis Population Description

39 patients were reviewed for toxicities for Cycle 2-5+. 11 patients out of the original 50 exited the study prior to Cycle 2.

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	39
Anemia	14 28%
Lymphopenia	19 38%
Pancytopenia	1 2%
Thrombocytopenia	11 22%
Arrhythmia	2 4%
Chest pain	1 2%
Hypertension	4 8%
Lower extremity edema	3 6%
Fatigue	30 60%
Fever	4 8%
Hand-foot skin reaction	20 40%
Mucositis	6 12%
Rash	12 24%
Skin pain	3 6%
Ascites	2 4%
Anorexia	14 28%
Diarrhea	15 30%
Nausea or vomiting	13 26%
Epistaxis or hemoptysis	1 2%
Cholangitis	1 2%
Elevated ALT level	9 18%
Elevated AST level	10 20%
Elevated AP level	15 30%
Elevated amylase level	7 14%
Elevated lipase level	9 18%
Elevated INR level	8 16%
Hyperbilirubinemia	11 22%
Hypoalbuminemia	14 28%
Infection	8 16%
Liver abscess	1 2%
Dizziness	1 2%
Headache	6 12%
Encephalopathy	3 6%
Nonspecific abdominal pain	22 44%
Musculoskeletal pain	17 34%
Right upper quadrant pain	10 20%
Pain - other	4 8%
Acute renal failure	1 2%
Death (disease progression)	2 4%

3. Secondary Outcome

Title	Efficacy Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) to Determine Response and Disease Control Rate
Description	Efficacy as assessed by radiographic tumor response using the RECIST criteria at baseline and at 6 months post the initiation of treatment. 33 out of the original 50 patients were evaluable at this time point, with 17 out of the 50 exiting prior to 6 months or were not assessable by RECIST criteria. Complete response (CR): Disappearance of all lesions targeted with therapy Partial Response (PR): at least 30% decrease in sum of longest diameter (LD) of targeted lesions Progressive Disease (PD): at least 20% increase in the sum of LD of targeted lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

33 out of the original 50 patients were evaluable for this outcome, with 17 out of the original 50 exiting prior to 6 months or were not assessable by RECIST criteria.

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	33
Complete Response	1 2%
Partial Response or Stable Disease	30 60%
Progressive Disease	2 4%
Disease control rate (CR + PR + SD)	31 62%

4. Secondary Outcome

Title	Efficacy Assessed by European Association for the Study of the Liver (EASL) Criteria to Determine Response and Disease Control Rate
Description	Efficacy as assessed by radiographic tumor response using the EASL criteria at baseline and at 6 months post the initiation of treatment. Complete response (CR): 100% tumor necrosis Partial Response (PR): more than 50% tumor necrosis Progressive Disease (PD): increase in tumor enhancement by more than 25% Stable Disease (SD): Cases that do not qualify for one of the above criteria
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

32 out of the 50 patients had imaging assessable by EASL criteria at 6 months - 18 out of the original 50 had exited prior to this time point or did not have applicable imaging.

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	32
Complete Response	7 14%
Partial Response	15 30%
Stable Disease	8 16%
Progressive Disease	2 4%
Disease control rate (CR + PR + SD)	30 60%

5. Secondary Outcome

Title	Efficacy - Median TTP After Combination Treatment With Sorafenib and TACE
Description	Time to progression (TTP) - defined as the time from initiation of therapy to disease progression (radiological). Median TTP calculated for all subjects and stratified by Barcelona Clinic Liver Cancer (BCLC) staging. 46 patients out of 50 were reviewed for this outcome. 3 patients were excluded because they underwent liver transplantation and 1 patient was excluded for hepatic resection.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Median TTP stratified by BCLC staging; 3 patients had BCLC stage A disease, 14 with stage B, and 29 with stage C.

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	46
Median TTP	13.9
Median TTP for BCLC stage A	27.6
Median TTP for BCLC stage B	24.7
Median TTP for BCLC stage C	9.5

6. Secondary Outcome

Title	Efficacy - Overall Survival (OS) After Combination Treatment With Sorafenib and TACE
Description	Overall survival was assessed with Kaplan-Meier estimates of survival, and the Mantel-Cox log-rank test was used to determine differences in survival. All 50 patients were included in survival analyses as all 50 received at least one dose of sorafenib.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	50
Median (Inter-Quartile Range) [months]	20.4

7. Secondary Outcome

Title	Efficacy - Factors Associated With Overall Survival (OS) After Combination Treatment With Sorafenib and TACE
Description	Overall survival was assessed with Kaplan-Meier estimates of survival, and the Mantel-Cox log-rank test was used to determine differences in survival.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	50
Median liver tumor burden >10%	2.60
Median tumor size > 10cm	2.12
ECOG performance status	2.45
BCLC stage	2.49

8. Other Pre-specified Outcome

Title	Estimated Percentage of Participants Surviving After One Year
Description	Percentage of study patients surviving after one year from initial treatment analyzed with Kaplan-Meier curve.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All 50 patients were included in survival analyses as all 50 received at least one dose of sorafenib.

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	50
Number [percentage of participants]	64 128%

9. Other Pre-specified Outcome

Title	Estimated Percentage of Participants Surviving After Three Year
Description	Percentage of study patients surviving after three years from initial treatment analyzed with Kaplan-Meier curve.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

All 50 patients were included in survival analyses as all 50 received at least one dose of sorafenib.

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	50
Number [percentage of participants]	19.6 39.2%

10. Other Pre-specified Outcome

Title	Median Overall Survival OS Stratified by BCLC Criteria
Description	Median overall survival stratified by Barcelona Clinic Liver Cancer (BCLC) staging as assessed by Kaplan-Meier estimator. Patients are grouped to stages A (early), B (intermediate), and C (advanced) according to stage of disease.
Time Frame	up to 4 years

Outcome Measure Data

Analysis Population Description

50 total participants received sorafenib on trial. 3 were classified as BCLC A, 16 as BCLC B, and 31 as BCLC C.

Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
Measure Participants	50
BCLC A	45.6
BCLC B	29.7
BCLC C	8.0

Adverse Events

Time Frame	Adverse events were collected for the entire duration of study participation, an average of 2 years. Participants remained on study until further treatment with sorafenib and TACE was deemed to not be beneficial.
Arm/Group Title	Sorafenib and Drug Eluting Beads
Arm/Group Description	single arm sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial LC Bead-TACE: LC Beads loaded with doxorubicin Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period
All Cause Mortality
	Sorafenib and Drug Eluting Beads
	Affected / at Risk (%)	# Events
Total	3/50 (6%)
Serious Adverse Events
	Sorafenib and Drug Eluting Beads
	Affected / at Risk (%)	# Events
Total	8/50 (16%)
Gastrointestinal disorders
Abdominal pain	1/50 (2%)	1
General disorders
Non-cardiac chest pain	2/50 (4%)	2
Overdose on pain medication	1/50 (2%)	1
Hepatobiliary disorders
Cholangitis	1/50 (2%)	1
Metabolism and nutrition disorders
Elevated creatinine	1/50 (2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor rupture	1/50 (2%)	1
Nervous system disorders
Encephalopathy	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	Sorafenib and Drug Eluting Beads
	Affected / at Risk (%)	# Events
Total	50/50 (100%)
Blood and lymphatic system disorders
Anemia	14/50 (28%)	27
Pancytopenia	1/50 (2%)	1
Cardiac disorders
Arrhythmia	4/50 (8%)	4
Gastrointestinal disorders
Mucositis	11/50 (22%)	17
Ascites	3/50 (6%)	5
Diarrhea	19/50 (38%)	34
Nausea or vomiting	24/50 (48%)	37
Hematochezia	2/50 (4%)	2
Liver abscess	1/50 (2%)	1
Nonspecific abdominal pain	23/50 (46%)	45
Pain - right upper quadrant	24/50 (48%)	34
General disorders
Non-cardiac chest pain	1/50 (2%)	1
Edema - lower extremity	12/50 (24%)	15
Fatigue	42/50 (84%)	72
Fever	15/50 (30%)	19
Pain - other	12/50 (24%)	16
Infections and infestations
Infection	8/50 (16%)	8
Investigations
Lymhopenia	24/50 (48%)	43
Thrombocytopenia	11/50 (22%)	19
Elevated ALT	25/50 (50%)	34
Elevated AST	24/50 (48%)	34
Elevated AP	17/50 (34%)	32
Elevated amylase	10/50 (20%)	17
Elevated lipase	15/50 (30%)	24
Elevated INR	16/50 (32%)	24
Hyperbilirubinemia	30/50 (60%)	41
Hypoalbuminemia	27/50 (54%)	41
Metabolism and nutrition disorders
Anorexia	28/50 (56%)	42
Musculoskeletal and connective tissue disorders
Pain - musculoskeletal	24/50 (48%)	41
Nervous system disorders
Dizziness	4/50 (8%)	5
Headache	9/50 (18%)	15
Encephalopathy	2/50 (4%)	2
Renal and urinary disorders
Acute kidney injury	2/50 (4%)	2
Respiratory, thoracic and mediastinal disorders
Epistaxis or hemoptysis	1/50 (2%)	2
Skin and subcutaneous tissue disorders
Hand foot skin reaction	23/50 (46%)	43
Rash	26/50 (52%)	38
Skin pain	4/50 (8%)	7
Vascular disorders
Common hepatic artery dissection	1/50 (2%)	1
Embolus or coagulopathy	1/50 (2%)	1
Hematoma	3/50 (6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.