Trial Outcomes & Findings for Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer (NCT NCT00813293)

NCT ID: NCT00813293

Last Updated: 2023-06-13

Results Overview

The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Up to day 50 from study enrollment (target 30 days after RFA)

Results posted on

2023-06-13

Participant Flow

Participants enrolled from June 2009 through August 2013.

Participant milestones

Participant milestones
Measure	Sorafenib Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Overall Study STARTED	10	10
Overall Study Started Treatment	9	10
Overall Study Evaluable RFA	7	8
Overall Study COMPLETED	9	9
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sorafenib Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Overall Study Intercurrent illness	1	0
Overall Study Adverse Event	0	1

Baseline Characteristics

Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sorafenib n=10 Participants Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo n=10 Participants Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Total n=20 Participants Total of all reporting groups
Age, Continuous	69 years STANDARD_DEVIATION 10 • n=5 Participants	66 years STANDARD_DEVIATION 11 • n=7 Participants	68 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Present Liver Cirrhosis	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Present Portal Vein Thrombosis	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Tumor Size - Short Axis	4.4 centimeters STANDARD_DEVIATION 1.3 • n=5 Participants	4.4 centimeters STANDARD_DEVIATION 1.4 • n=7 Participants	4.4 centimeters STANDARD_DEVIATION 1.3 • n=5 Participants
Tumor Size - Long Axis	4.9 centimeters STANDARD_DEVIATION 1.7 • n=5 Participants	5.3 centimeters STANDARD_DEVIATION 1.3 • n=7 Participants	5.1 centimeters STANDARD_DEVIATION 1.5 • n=5 Participants

PRIMARY outcome

Timeframe: Up to day 50 from study enrollment (target 30 days after RFA)

Population: The analysis population is comprised of all participants who completed treatment ending with day 10 RFA.

The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

Outcome measures

Outcome measures
Measure	Sorafenib n=9 Participants Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo n=9 Participants Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Coagulation Zone Diameter-Short Axis	36.0 millimeters Standard Deviation 7.8	35.1 millimeters Standard Deviation 8.8

PRIMARY outcome

Timeframe: Up to day 50 from study enrollment (target 30 days after RFA)

Population: The analysis population is comprised of all participants who completed treatment ending with RFA.

The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

Outcome measures

Outcome measures
Measure	Sorafenib n=9 Participants Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo n=9 Participants Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Coagulation Zone Diameter-Long Axis	42.4 millimeters Standard Deviation 9.2	44.1 millimeters Standard Deviation 7.8

PRIMARY outcome

Timeframe: Up to day 50 from study enrollment (target 30 days after RFA)

Population: The analysis population is comprised of all participants who completed treatment ending with RFA.

The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

Outcome measures

Outcome measures
Measure	Sorafenib n=9 Participants Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo n=9 Participants Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Coagulation Zone Volume	30.7 centimeters^3 Standard Deviation 24.6	30.5 centimeters^3 Standard Deviation 21.5

SECONDARY outcome

Timeframe: Up to day 14 since enrollment

Population: The analysis population is comprised of all enrolled participants.

Feasibility rate is defined as the percentage of participants completing radiofrequency ablation following 9 days of sorafenib or placebo therapy.

Outcome measures

Outcome measures
Measure	Sorafenib n=10 Participants Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo n=10 Participants Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Feasibility Rate	90 percentage of particpants Interval 60.6 to 99.5	90 percentage of particpants Interval 60.6 to 99.5

SECONDARY outcome

Timeframe: Day 9

Population: The analysis population is comprised of all treated participants.

AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related up to day 9 of study drug treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple different AE types within a grade.

Outcome measures

Outcome measures
Measure	Sorafenib n=9 Participants Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo n=10 Participants Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) by Day 9	8 adverse events	4 adverse events

SECONDARY outcome

Timeframe: Up to day 14 (target day 10 RFA)

Population: The analysis population is comprised of all participants who completed treatment ending with RFA.

AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related on day of RFA treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple AE types within a grade.

Outcome measures

Outcome measures
Measure	Sorafenib n=9 Participants Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo n=9 Participants Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) on Day of Radiofrequency Ablation (RFA)	5 adverse events	4 adverse events

SECONDARY outcome

Timeframe: Up to day 40 post RFA (target 30 days)

Population: The analysis population is comprised of all treated participants who were evaluable for AEs at day40.

AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related one month after RFA treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple AE types within a grade.

Outcome measures

Outcome measures
Measure	Sorafenib n=8 Participants Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).	Placebo n=8 Participants Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) One Month After Radiofrequency Ablation (RFA)	8 adverse events	4 adverse events

Adverse Events

Sorafenib

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sorafenib n=9 participants at risk Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min). Sorafenib radiofrequency ablation	Placebo n=10 participants at risk Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min). radiofrequency ablation
Investigations Leukocytes	11.1% 1/9 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.	0.00% 0/10 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.
Investigations Lymphopenia	11.1% 1/9 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.	0.00% 0/10 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.
Investigations AST, SGOT	11.1% 1/9 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.	0.00% 0/10 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.
Investigations Bilirubin	11.1% 1/9 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.	0.00% 0/10 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.
Hepatobiliary disorders Liver, hemorrhage	0.00% 0/9 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.	10.0% 1/10 • Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.

Other adverse events

Additional Information

Andrea Bullock MD, MPH

Beth Israel Deasoness Medical Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place