Trial Outcomes & Findings for Chemoembolization With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery (NCT NCT01004978)

Last Updated: 2024-01-03

Results Overview

PFS is defined to be the time from randomization to progression or death without evidence of progression. For cases without documentation of progression, follow-up will be censored at the date of last disease assessment without progression, unless death occurs within 4 months following the date last known progression-free, in which case the death will be counted as an event. Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

235 participants

Primary outcome timeframe

Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years

Results posted on

2024-01-03

Participant Flow

This study activated on October 28, 2009 and closed to accrual on November 19, 2014 due to poor enrollment. A total of 235 patients were randomized.

Participant milestones

Participant milestones
Measure	Arm A (Sorafenib and TACE) Patients receive sorafenib tosylate at 400mg PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (Placebo and TACE) Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.
Overall Study STARTED	118	117
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	118	117

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Sorafenib and TACE) Patients receive sorafenib tosylate at 400mg PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (Placebo and TACE) Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.
Overall Study Disease progression	31	48
Overall Study Adverse Event	42	22
Overall Study Death	3	2
Overall Study Withdrawal by Subject	16	16
Overall Study Alternative therapy	4	8
Overall Study Physician Decision	6	3
Overall Study Other complicating disease	2	2
Overall Study Protocol Violation	2	3
Overall Study Non-compliance	3	2
Overall Study Ineligible	1	0
Overall Study Unblinded	0	1
Overall Study Performance status worsening	0	1
Overall Study Never started treatment	8	9

Baseline Characteristics

Chemoembolization With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Sorafenib and TACE) n=118 Participants Patients receive sorafenib tosylate at 400mg PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (Placebo and TACE) n=117 Participants Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.	Total n=235 Participants Total of all reporting groups
Age, Continuous	62.1 years n=5 Participants	64.1 years n=7 Participants	62.8 years n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	104 Participants n=5 Participants	101 Participants n=7 Participants	205 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	99 Participants n=5 Participants	98 Participants n=7 Participants	197 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	29 Participants n=5 Participants	22 Participants n=7 Participants	51 Participants n=5 Participants
Race (NIH/OMB) White	71 Participants n=5 Participants	78 Participants n=7 Participants	149 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years

Population: All randomized patients

Outcome measures

Outcome measures
Measure	Arm A (Sorafenib and TACE) n=118 Participants Patients receive sorafenib tosylate at 400mg PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (Placebo and TACE) n=117 Participants Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.
Progression-free Survival (PFS)	9.3 months Interval 6.8 to 11.9	8.4 months Interval 5.4 to 10.9

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years and then every 6 months for 2 years

Population: All randomized patients

Overall survival (OS) is defined as time from randomization to death from any cause, censoring cases who had not died at the date last known alive.

Outcome measures

Outcome measures
Measure	Arm A (Sorafenib and TACE) n=118 Participants Patients receive sorafenib tosylate at 400mg PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (Placebo and TACE) n=117 Participants Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.
Overall Survival (OS)	19.8 months Interval 16.8 to 23.7	19.9 months Interval 13.5 to 27.2

SECONDARY outcome

Timeframe: Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years

Population: Only patients with extra-hepatic progression (as well as those with both intra- and extra-hepatic progression) are included in this analysis

PFS is defined to be the time from randomization to progression or death without evidence of progression. Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. For patients with progressive disease, the progression was classified as either intra- or extra-hepatic or both intra- and extra-hepatic. Patients with both intra- and extra-hepatic progression were considered as having extra-hepatic progression. This analysis was performed among patients with extra-hepatic progression.

Outcome measures

Outcome measures
Measure	Arm A (Sorafenib and TACE) n=19 Participants Patients receive sorafenib tosylate at 400mg PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (Placebo and TACE) n=11 Participants Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.
Progression-free Survival (PFS) Among Patients With Extra-hepatic Progression	6.83 months Interval 3.7 to 15.7	5.6 months Interval 5.0 to 9.7

SECONDARY outcome

Timeframe: Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years

Population: Only patients with intra-hepatic progression are included in this analysis.

PFS is defined to be the time from randomization to progression or death without evidence of progression. Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. For patients with progressive disease, the progression was classified as either intra- or extra-hepatic or both intra- and extra-hepatic. This analysis was performed among patients with intra-hepatic progression.

Outcome measures

Outcome measures
Measure	Arm A (Sorafenib and TACE) n=53 Participants Patients receive sorafenib tosylate at 400mg PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (Placebo and TACE) n=64 Participants Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.
Progression-free Survival (PFS) Among Patients With Intra-hepatic Progression	8.5 months Interval 5.8 to 11.1	7.8 months Interval 4.9 to 10.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline, days 1, 8 and 15 of cycle 1 sorafenib, 3-5 days prior to 2nd and 3rd TACE

This analysis will be performed across a few ECOG-ACRIN studies of sorafenib to evaluate the association between genotypes that are related with sorafenib activity and clinical outcomes.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: at 4 months and 8 months Assessed at 4 months and 8 months following initial chemoembolization

Response was determined using the European Association for the Study of the Liver (EASL) criteria, which was recommended as an alternative to RECIST for grading therapeutic response of advanced hepatocellular carcinoma (HCC). The EASL criteria use the longest dimension of enhancing tumor as the primary metric for gauging tumor response. The Kappa statistics will be applied to assess agreement between readers.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years

Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. For patients with progressive disease, the progression was classified as either intra- or extra-hepatic or both intra- and extra-hepatic. OS is defined as the time from randomization to death or date last known alive.

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Sorafenib and TACE)

Serious events: 65 serious events

Other events: 22 other events

Deaths: 85 deaths

Arm B (Placebo and TACE)

Serious events: 41 serious events

Other events: 21 other events

Deaths: 88 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm A (Sorafenib and TACE) n=110 participants at risk Patients receive sorafenib tosylate PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (Placebo and TACE) n=108 participants at risk Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.
Blood and lymphatic system disorders Anemia	5.5% 6/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	10.2% 11/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
General disorders Fatigue	13.6% 15/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	12.0% 13/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia	7.3% 8/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	0.93% 1/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Gastrointestinal disorders Abdominal pain	5.5% 6/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	6.5% 7/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Gastrointestinal disorders Diarrhea	7.3% 8/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	2.8% 3/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Gastrointestinal disorders Nausea	7.3% 8/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	7.4% 8/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Investigations Platelet count decreased	8.2% 9/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	8.3% 9/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Investigations Weight loss	6.4% 7/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	0.93% 1/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Investigations White blood cell decreased	5.5% 6/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	1.9% 2/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Metabolism and nutrition disorders Anorexia	8.2% 9/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	0.93% 1/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.
Metabolism and nutrition disorders Hypoalbuminemia	1.8% 2/110 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.	5.6% 6/108 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, and then every 6 months up to 4 years Adverse events were assessed among all treated patients. All-cause mortality was evaluated among all randomized patients.

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60