A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT00108953
Collaborator
(none)
96
28
2
36
3.4
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of doxorubicin plus sorafenib versus doxorubicin plus placebo in patients with advanced hepatocellular carcinoma (HCC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
In addition to the key secondary outcome parameters the following parameters will be assessed in an exploratory manner: relative time to progression (TTP), time to symptomatic progression (TTSP), response rate (RR) and overall survival between the 2 study populations.
The possible and potential predictive assays of clinical benefit through an assessment of the correlation between the defined baseline characteristics and key clinical endpoints.
The safety and tolerability will be assessed in the adverse event section. Doxorubicin pharmacokinetics in HCC patients treated with sorafenib versus placebo will be compared and the pharmacokinetic data will be correlated with doxorubicin-related adverse events (i.e., cardiotoxicity).
Study Design
Study Type:
Interventional
Actual Enrollment
:
96 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized Controlled Study of BAY43-9006 in Combination With Doxorubicin Versus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma.
Study Start Date
:
Apr 1, 2005
Actual Primary Completion Date
:
Apr 1, 2008
Actual Study Completion Date
:
Apr 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sorafenib + Doxorubicin "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Multi kinase inhibitor plus Chemotherapy
|
| Active Comparator: Placebo + Doxorubicin "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
Drug: Doxorubicin/Placebo
Chemotherapy plus Placebo
|
Outcome Measures
Primary Outcome Measures
- Time to Progression (TTP) [from date of randomization of the first patient until 3 years later]
TTP was defined as the time from randomization to radiological disease progression by independent assessment.
Secondary Outcome Measures
- Overall Survival [from date of randomization of the first patient until 3 years later]
The time from date of randomization to date of death
- Progression Free Survival (PFS) [from date of randomization of the first patient until 3 years later]
Time from the date of randomization to the date of the first documented radiological progression (as defined per independent central radiological assessment) or death, whichever occurs first
- Percentage of Participants in Each Category of Best Tumor Response [achieved during treatment or within 30 days after termination of active therapy]
Percentage of participants with complete or partial response (CR or PR) confirmed according to Response Evaluation Criteria in Solid Tumors (RECIST) and achieved during treatment or 30 days after end of treatment. CR: disappearance of all clinical and radiological tumor lesions. PR: at least 30% decrease in sum of the longest diameters of tumor lesions. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.
- Time to Symptomatic Progression (TTSP) [from date of randomization of the first patient until 3 years later]
Time from date of randomization to date of first documented symptomatic progression defined by Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index-8 (FHSI-8) assessment
- Duration of Response [from date of randomization of the first patient until 3 years later]
Time from date of first objective response (complete response [CR] or partial response [PR]) to date progression is first documented (as defined per independent central radiological assessment) or death, whichever occurs first
- Time to Response (TTR) [from date of randomization until 3 years later at end of study]
Time from date of randomization to date of first objective response (complete response [CR] or partial response [PR]) is documented and confirmed according to RECIST criteria
- Percentage of Participants for Whom Disease Control Was Achieved [from date of randomization to end of treatment plus 30 days]
Participants with disease control: those who have as best response complete response (CR), partial response (PR) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients who have a life expectancy of at least 12 weeks
-
Patients with advanced HCC (unresectable, and/or metastatic) which has been histologically or cytologically documented
-
Patients must have at least one tumor lesion that meets both of the following criteria:
-
can be accurately measured in at least one dimension according to Response Evaluation Criteria in Solid Tumors (RECIST)
-
has not been previously treated with local therapy
-
Patients who have received local therapy except chemoembolization, such as surgery, radiation therapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible, provided that they either have a target lesion which has not been subjected to local therapy and/or the target lesion(s) within the field of the local therapy has shown an increase of 25% in the size. Local therapy must be completed at least 4 weeks prior to the baseline scan
-
Patients who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion Criteria:
-
Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted
-
History of cardiac disease
-
Serious myocardial dysfunction
-
Active, clinically serious infections
-
Known history of Human Immunodeficiency Virus (HIV) infection
-
Known Central Nervous System (CNS) tumors including metastatic brain disease
-
Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | 35294 | |
| 2 | Beverly Hills | California | United States | 90211-1850 | |
| 3 | Orange | California | United States | 92668-3298 | |
| 4 | Palo Alto | California | United States | 94304-1207 | |
| 5 | San Francisco | California | United States | 94115 | |
| 6 | San Francisco | California | United States | 94121 | |
| 7 | Sylmar | California | United States | 91342 | |
| 8 | Miami | Florida | United States | 33136 | |
| 9 | Lafayette | Louisiana | United States | 70506 | |
| 10 | Minneapolis | Minnesota | United States | 55455 | |
| 11 | Hackensack | New Jersey | United States | 07601 | |
| 12 | New York | New York | United States | 10065 | |
| 13 | Rochester | New York | United States | 14642 | |
| 14 | Nashville | Tennessee | United States | 37203 | |
| 15 | Seattle | Washington | United States | 98101 | |
| 16 | Buenos Aires | Ciudad Auton. de Buenos Aires | Argentina | C1264AAA | |
| 17 | Neuquen | Neuquén | Argentina | Q8300HDH | |
| 18 | Buenos Aires | Argentina | |||
| 19 | Toronto | Ontario | Canada | M5G 2M9 | |
| 20 | Hong Kong | Hong Kong | |||
| 21 | Kazan | Russian Federation | 420111 | ||
| 22 | Kirov | Russian Federation | 610002 | ||
| 23 | Krasnodar | Russian Federation | 350040 | ||
| 24 | Maidstone | Kent | United Kingdom | ME16 9QQ | |
| 25 | Bebington | Merseyside | United Kingdom | CH63 4JY | |
| 26 | Birmingham | West Midlands | United Kingdom | B15 2TT | |
| 27 | London | United Kingdom | W12 0HS | ||
| 28 | Manchester | United Kingdom | M20 4BX |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00108953
Other Study ID Numbers:
- 11546
- 2004-001770-40
First Posted:
Apr 22, 2005
Last Update Posted:
Oct 31, 2014
Last Verified:
Oct 1, 2014
Keywords provided by Bayer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Enrollment started on 13 Apr 2005 and the last study contact occurred on 11 Apr 2008. The study was conducted at 25 active centers in 6 countries (Argentina, Canada, Hong Kong, Russia, United Kingdom, and United States.) |
|---|---|
| Pre-assignment Detail | 140 patients were screened, with 44 screen failures. The intent-to-treat (ITT) population (primary efficacy analysis) includes all randomized patients (96). The Safety population includes all patients who received at least 1 dose of study drug (95). The study consists of 2 periods: treatment period (not fixed but ended by any event) and follow-up. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Period Title: Treatment Period | ||
| STARTED | 47 | 49 |
| COMPLETED | 47 | 49 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Treatment Period | ||
| STARTED | 40 | 45 |
| COMPLETED | 11 | 12 |
| NOT COMPLETED | 29 | 33 |
Baseline Characteristics
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin | Total |
|---|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | Total of all reporting groups |
| Overall Participants | 47 | 49 | 96 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) |
66
|
65
|
65
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
16
34%
|
7
14.3%
|
23
24%
|
| Male |
31
66%
|
42
85.7%
|
73
76%
|
| Child Pugh Status (participants) [Number] | |||
| 5 (Child-Pugh A) |
30
63.8%
|
28
57.1%
|
58
60.4%
|
| 6 (Child-Pugh A) |
17
36.2%
|
19
38.8%
|
36
37.5%
|
| 7 (Child-Pugh B) |
0
0%
|
2
4.1%
|
2
2.1%
|
| >7 |
0
0%
|
0
0%
|
0
0%
|
| Eastern Cooperative Group performance status (ECOG PS) at study entry (participants) [Number] | |||
| Grade 0 |
22
46.8%
|
16
32.7%
|
38
39.6%
|
| Grade 1 |
18
38.3%
|
25
51%
|
43
44.8%
|
| Grade 2 |
4
8.5%
|
3
6.1%
|
7
7.3%
|
| Grade 3 |
0
0%
|
1
2%
|
1
1%
|
| missing |
3
6.4%
|
4
8.2%
|
7
7.3%
|
| Tumor burden: Extrahepatic spread (participants) [Number] | |||
| yes |
24
51.1%
|
32
65.3%
|
56
58.3%
|
| no |
23
48.9%
|
17
34.7%
|
40
41.7%
|
| Tumor burden: Macroscopic vascular invasion (participants) [Number] | |||
| yes |
13
27.7%
|
16
32.7%
|
29
30.2%
|
| no |
33
70.2%
|
32
65.3%
|
65
67.7%
|
| missing |
1
2.1%
|
1
2%
|
2
2.1%
|
Outcome Measures
| Title | Time to Progression (TTP) |
|---|---|
| Description | TTP was defined as the time from randomization to radiological disease progression by independent assessment. |
| Time Frame | from date of randomization of the first patient until 3 years later |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population, primary population for efficacy analysis, includes all randomized patients. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Measure Participants | 47 | 49 |
| Median (95% Confidence Interval) [days] |
263
|
147
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib + Doxorubicin, Placebo + Doxorubicin |
|---|---|---|
| Comments | The comparison between the 2 groups is done using the log rank test stratified by tumor burden. The null hypothesis is: TTP is the same in both treatment groups. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.016 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio, log |
| Estimated Value | 0.6 | |
| Confidence Interval |
() 95% 0.33 to 0.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio: nexavar+doxorubicin over placebo+doxorubicin | |
| Title | Overall Survival |
|---|---|
| Description | The time from date of randomization to date of death |
| Time Frame | from date of randomization of the first patient until 3 years later |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population, primary population for efficacy analysis, includes all randomized patients. The table below gives the lower and upper limit of the confidence interval; 999999999 = not estimable. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Measure Participants | 47 | 49 |
| Median (95% Confidence Interval) [days] |
418
|
199
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib + Doxorubicin, Placebo + Doxorubicin |
|---|---|---|
| Comments | The comparison between the 2 groups is done using the log rank test stratified by tumor burden. The null hypothesis is: TTP is the same in both treatment groups | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.52 | |
| Confidence Interval |
() 95% 0.37 to 0.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio: nexavar+doxorubicin over placebo+doxorubicin | |
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | Time from the date of randomization to the date of the first documented radiological progression (as defined per independent central radiological assessment) or death, whichever occurs first |
| Time Frame | from date of randomization of the first patient until 3 years later |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population, primary population for efficacy analysis, includes all randomized patients. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY 43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY 43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Measure Participants | 47 | 49 |
| Median (95% Confidence Interval) [days] |
242
|
85
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib + Doxorubicin, Placebo + Doxorubicin |
|---|---|---|
| Comments | The comparison between the 2 groups is done using the log rank test stratified by tumor burden. The null hypothesis is: TTP is the same in both treatment groups | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.018 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.61 | |
| Confidence Interval |
() 95% 0.45 to 0.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio: nexavar+doxorubicin over placebo+doxorubicin | |
| Title | Percentage of Participants in Each Category of Best Tumor Response |
|---|---|
| Description | Percentage of participants with complete or partial response (CR or PR) confirmed according to Response Evaluation Criteria in Solid Tumors (RECIST) and achieved during treatment or 30 days after end of treatment. CR: disappearance of all clinical and radiological tumor lesions. PR: at least 30% decrease in sum of the longest diameters of tumor lesions. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease. |
| Time Frame | achieved during treatment or within 30 days after termination of active therapy |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population, primary population for efficacy analysis, includes all randomized patients. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Measure Participants | 47 | 49 |
| Complete Response (CR) |
0.0
0%
|
2.0
4.1%
|
| Partial Response (PR) |
4.3
9.1%
|
0.0
0%
|
| Stable Disease (SD) |
66.0
140.4%
|
49.0
100%
|
| Title | Time to Symptomatic Progression (TTSP) |
|---|---|
| Description | Time from date of randomization to date of first documented symptomatic progression defined by Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index-8 (FHSI-8) assessment |
| Time Frame | from date of randomization of the first patient until 3 years later |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population, primary population for efficacy analysis, includes all randomized patients. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY 43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY 43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Measure Participants | 47 | 49 |
| Median (95% Confidence Interval) [days] |
208
|
152
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib + Doxorubicin, Placebo + Doxorubicin |
|---|---|---|
| Comments | The comparison between the 2 groups is done using the log rank test stratified by tumor burden. The null hypothesis is: TTP is the same in both treatment groups | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.65 | |
| Confidence Interval |
() 95% 0.40 to 1.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio: nexavar+doxorubicin over placebo+doxorubicin | |
| Title | Duration of Response |
|---|---|
| Description | Time from date of first objective response (complete response [CR] or partial response [PR]) to date progression is first documented (as defined per independent central radiological assessment) or death, whichever occurs first |
| Time Frame | from date of randomization of the first patient until 3 years later |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population, primary population for efficacy analysis, includes all randomized patients. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Measure Participants | 47 | 49 |
| Median (Full Range) [days] |
199
|
68
|
| Title | Time to Response (TTR) |
|---|---|
| Description | Time from date of randomization to date of first objective response (complete response [CR] or partial response [PR]) is documented and confirmed according to RECIST criteria |
| Time Frame | from date of randomization until 3 years later at end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population, primary population for efficacy analysis, includes all randomized patients. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Measure Participants | 47 | 49 |
| Median (Full Range) [days] |
134
|
40
|
| Title | Percentage of Participants for Whom Disease Control Was Achieved |
|---|---|
| Description | Participants with disease control: those who have as best response complete response (CR), partial response (PR) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST) |
| Time Frame | from date of randomization to end of treatment plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population, primary population for efficacy analysis, includes all randomized patients. |
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin |
|---|---|---|
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) |
| Measure Participants | 47 | 49 |
| Number [Percentage of participants] |
63.8
135.7%
|
30.6
62.4%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | The following abbreviations were used in the Adverse Event section: Common toxicity criteria for adverse events (CTCAE) Absolute neutrophil count (ANC) Alanine aminotransferase (AST) Gastrointestinal (GI) Not otherwise specified (NOS) International normalized ratio (INR) Alanine aminotransferase (ALT) | |||
| Arm/Group Title | Sorafenib + Doxorubicin | Placebo + Doxorubicin | ||
| Arm/Group Description | "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) | ||
All Cause Mortality |
||||
| Sorafenib + Doxorubicin | Placebo + Doxorubicin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Sorafenib + Doxorubicin | Placebo + Doxorubicin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/47 (40.4%) | 20/48 (41.7%) | ||
| Blood and lymphatic system disorders | ||||
| Neutrophils | 2/47 (4.3%) | 0/48 (0%) | ||
| Hemoglobin | 1/47 (2.1%) | 1/48 (2.1%) | ||
| Cardiac disorders | ||||
| Supraventricular Arrhythmia, Atrial Fibrillation | 1/47 (2.1%) | 1/48 (2.1%) | ||
| Supraventricular Arrhythmia, Sinus Tachycardia | 1/47 (2.1%) | 0/48 (0%) | ||
| Cardiac Ischemia/Infarction | 2/47 (4.3%) | 0/48 (0%) | ||
| Hypotension | 0/47 (0%) | 1/48 (2.1%) | ||
| Gastrointestinal disorders | ||||
| Dehydration | 2/47 (4.3%) | 2/48 (4.2%) | ||
| Diarrhea | 1/47 (2.1%) | 2/48 (4.2%) | ||
| Vomiting | 3/47 (6.4%) | 0/48 (0%) | ||
| Mucositis (Clinical Exam), Oral Cavity | 1/47 (2.1%) | 1/48 (2.1%) | ||
| Nausea | 2/47 (4.3%) | 0/48 (0%) | ||
| Constipation | 1/47 (2.1%) | 0/48 (0%) | ||
| Ileus | 1/47 (2.1%) | 0/48 (0%) | ||
| General disorders | ||||
| Death not associated with CTCAE term, Disease Progression NOS | 3/47 (6.4%) | 10/48 (20.8%) | ||
| Fever | 0/47 (0%) | 1/48 (2.1%) | ||
| Fatigue | 1/47 (2.1%) | 0/48 (0%) | ||
| Pain, Back | 2/47 (4.3%) | 1/48 (2.1%) | ||
| Pain, Abdomen NOS | 2/47 (4.3%) | 1/48 (2.1%) | ||
| Pain, Chest/Thorax NOS | 1/47 (2.1%) | 0/48 (0%) | ||
| Pain, Liver | 1/47 (2.1%) | 0/48 (0%) | ||
| Hepatobiliary disorders | ||||
| Liver Dysfunction | 1/47 (2.1%) | 0/48 (0%) | ||
| Hepathobilary - other | 0/47 (0%) | 1/48 (2.1%) | ||
| Infections and infestations | ||||
| Febrile Neutropenia | 1/47 (2.1%) | 5/48 (10.4%) | ||
| Infection with normal ANC, Skin (Cellulitis) | 2/47 (4.3%) | 0/48 (0%) | ||
| Infection (Documented Clinically), Blood | 1/47 (2.1%) | 0/48 (0%) | ||
| Infection (Documented Clinically), Kidney | 1/47 (2.1%) | 0/48 (0%) | ||
| Infection (Documented Clinically), Lung (Pneumonia) | 0/47 (0%) | 1/48 (2.1%) | ||
| Infection (Documented Clinically), Skin (Cellulitis) | 1/47 (2.1%) | 0/48 (0%) | ||
| Infection with normal ANC, Soft Tissue NOS | 0/47 (0%) | 1/48 (2.1%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperkalemia | 2/47 (4.3%) | 0/48 (0%) | ||
| Lipase | 1/47 (2.1%) | 1/48 (2.1%) | ||
| Bilirubin (Hyperbilirubinemia) | 1/47 (2.1%) | 0/48 (0%) | ||
| Hypercalcemia | 1/47 (2.1%) | 0/48 (0%) | ||
| Nervous system disorders | ||||
| Neurology - other | 0/47 (0%) | 1/48 (2.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea (Shortness of Breath) | 2/47 (4.3%) | 1/48 (2.1%) | ||
| Hiccoughs | 1/47 (2.1%) | 0/48 (0%) | ||
| Vascular disorders | ||||
| Hemorrhage, GI, Stomach | 1/47 (2.1%) | 0/48 (0%) | ||
| Hemorrhage, GI, Upper GI NOS | 1/47 (2.1%) | 0/48 (0%) | ||
| Thrombosis/Thrombus/Embolism | 1/47 (2.1%) | 1/48 (2.1%) | ||
| Artery Injury, Visceral | 1/47 (2.1%) | 0/48 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Sorafenib + Doxorubicin | Placebo + Doxorubicin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/47 (100%) | 48/48 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Neutrophils | 31/47 (66%) | 29/48 (60.4%) | ||
| Hemoglobin | 15/47 (31.9%) | 15/48 (31.3%) | ||
| Leukocytes | 10/47 (21.3%) | 9/48 (18.8%) | ||
| Edema: Limb | 15/47 (31.9%) | 14/48 (29.2%) | ||
| Blood Other | 6/47 (12.8%) | 7/48 (14.6%) | ||
| Platelets | 7/47 (14.9%) | 9/48 (18.8%) | ||
| INR | 0/47 (0%) | 3/48 (6.3%) | ||
| Cardiac disorders | ||||
| Supraventricular Arrhythmia, Sinus Tachycardia | 4/47 (8.5%) | 0/48 (0%) | ||
| Hypertension | 8/47 (17%) | 0/48 (0%) | ||
| Hypotension | 0/47 (0%) | 4/48 (8.3%) | ||
| Left Ventricular Systolic Dysfunction | 9/47 (19.1%) | 0/48 (0%) | ||
| Eye disorders | ||||
| Ocular- Other | 4/47 (8.5%) | 0/48 (0%) | ||
| Watery Eye | 3/47 (6.4%) | 0/48 (0%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 27/47 (57.4%) | 27/48 (56.3%) | ||
| Constipation | 21/47 (44.7%) | 21/48 (43.8%) | ||
| Anorexia | 24/47 (51.1%) | 14/48 (29.2%) | ||
| Diarrhea | 25/47 (53.2%) | 12/48 (25%) | ||
| Mucositis (Functional/Symptomatic), Oral Cavity | 11/47 (23.4%) | 14/48 (29.2%) | ||
| GI - other | 13/47 (27.7%) | 7/48 (14.6%) | ||
| Mucositis (Clinical Exam), Oral Cavity | 10/47 (21.3%) | 6/48 (12.5%) | ||
| Taste Alteration | 10/47 (21.3%) | 5/48 (10.4%) | ||
| Vomiting | 17/47 (36.2%) | 10/48 (20.8%) | ||
| Ascites | 4/47 (8.5%) | 6/48 (12.5%) | ||
| Distention | 5/47 (10.6%) | 6/48 (12.5%) | ||
| Dry Mouth | 4/47 (8.5%) | 4/48 (8.3%) | ||
| Dysphagia | 7/47 (14.9%) | 0/48 (0%) | ||
| Flatulence | 3/47 (6.4%) | 4/48 (8.3%) | ||
| Hemorrhoids | 0/47 (0%) | 3/48 (6.3%) | ||
| Heartburn | 5/47 (10.6%) | 3/48 (6.3%) | ||
| Teeth | 3/47 (6.4%) | 0/48 (0%) | ||
| Liver Dysfunction | 0/47 (0%) | 3/48 (6.3%) | ||
| General disorders | ||||
| Fatigue | 39/47 (83%) | 32/48 (66.7%) | ||
| Insomnia | 13/47 (27.7%) | 8/48 (16.7%) | ||
| Pain, Abdomen NOS | 18/47 (38.3%) | 15/48 (31.3%) | ||
| Pain, Back | 14/47 (29.8%) | 7/48 (14.6%) | ||
| Fever | 4/47 (8.5%) | 4/48 (8.3%) | ||
| Weight Loss | 9/47 (19.1%) | 7/48 (14.6%) | ||
| Constitutional Symptoms- Other | 7/47 (14.9%) | 0/48 (0%) | ||
| Rigors/Chills | 5/47 (10.6%) | 0/48 (0%) | ||
| Sweating | 3/47 (6.4%) | 4/48 (8.3%) | ||
| Pain, Chest Wall | 3/47 (6.4%) | 3/48 (6.3%) | ||
| Pain, Extremity-Limb | 3/47 (6.4%) | 0/48 (0%) | ||
| Pain, Head/Headache | 9/47 (19.1%) | 6/48 (12.5%) | ||
| Pain, Joint | 9/47 (19.1%) | 3/48 (6.3%) | ||
| Pain, Muscle | 6/47 (12.8%) | 0/48 (0%) | ||
| Pain, Other | 5/47 (10.6%) | 3/48 (6.3%) | ||
| Pain, Liver | 6/47 (12.8%) | 3/48 (6.3%) | ||
| Pain, Middle Ear | 3/47 (6.4%) | 0/48 (0%) | ||
| Pain, Pain NOS | 3/47 (6.4%) | 0/48 (0%) | ||
| Pain, Stomach | 3/47 (6.4%) | 0/48 (0%) | ||
| Pain, Throat/Pharynx/Larynx | 3/47 (6.4%) | 0/48 (0%) | ||
| Immune system disorders | ||||
| Rhinits | 4/47 (8.5%) | 5/48 (10.4%) | ||
| Infections and infestations | ||||
| Infection(Documented Clinically), Oral cavity - gums | 6/47 (12.8%) | 3/48 (6.3%) | ||
| Febrile Neutropenia | 0/47 (0%) | 3/48 (6.3%) | ||
| Infection- Other | 3/47 (6.4%) | 3/48 (6.3%) | ||
| Metabolism and nutrition disorders | ||||
| Bilirubin (Hyperbilirubinemia) | 15/47 (31.9%) | 15/48 (31.3%) | ||
| AST | 11/47 (23.4%) | 7/48 (14.6%) | ||
| Alkaline Phosphatase | 5/47 (10.6%) | 7/48 (14.6%) | ||
| ALT | 8/47 (17%) | 4/48 (8.3%) | ||
| Hypercalcemia | 0/47 (0%) | 3/48 (6.3%) | ||
| Hyperglycemia | 0/47 (0%) | 3/48 (6.3%) | ||
| Hypoalbuminemia | 3/47 (6.4%) | 3/48 (6.3%) | ||
| Hypophosphatemia | 0/47 (0%) | 3/48 (6.3%) | ||
| Hyperkalemia | 3/47 (6.4%) | 0/48 (0%) | ||
| Hypocalcemia | 3/47 (6.4%) | 0/48 (0%) | ||
| Metabolic/Lab- Other | 3/47 (6.4%) | 5/48 (10.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal- Other | 8/47 (17%) | 4/48 (8.3%) | ||
| Nervous system disorders | ||||
| Dizziness | 10/47 (21.3%) | 4/48 (8.3%) | ||
| Mood Alteration, Anxiety | 3/47 (6.4%) | 3/48 (6.3%) | ||
| Mood Alteration, Depression | 4/47 (8.5%) | 0/48 (0%) | ||
| Neuropathy: sensory | 7/47 (14.9%) | 4/48 (8.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 13/47 (27.7%) | 9/48 (18.8%) | ||
| Hiccoughs | 3/47 (6.4%) | 0/48 (0%) | ||
| Nasal/Paranasal Reactions | 0/47 (0%) | 4/48 (8.3%) | ||
| Pulmonary- Other | 5/47 (10.6%) | 3/48 (6.3%) | ||
| Dyspnea(Shortness of Breath) | 8/47 (17%) | 8/48 (16.7%) | ||
| Voice Changes | 5/47 (10.6%) | 0/48 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 24/47 (51.1%) | 25/48 (52.1%) | ||
| Rash/Desquamation | 18/47 (38.3%) | 8/48 (16.7%) | ||
| Hand-Foot Skin Reaction | 14/47 (29.8%) | 0/48 (0%) | ||
| Dry Skin | 10/47 (21.3%) | 4/48 (8.3%) | ||
| Acne | 3/47 (6.4%) | 0/48 (0%) | ||
| Bruising | 6/47 (12.8%) | 3/48 (6.3%) | ||
| Nail changes | 5/47 (10.6%) | 0/48 (0%) | ||
| Dermatology- Other | 8/47 (17%) | 6/48 (12.5%) | ||
| Pruritus | 9/47 (19.1%) | 3/48 (6.3%) | ||
| Flushing | 3/47 (6.4%) | 0/48 (0%) | ||
| Vascular disorders | ||||
| Hemorrhage, GI, Oral Cavity | 3/47 (6.4%) | 0/48 (0%) | ||
| Hemorrhage Pulmonary, Nose | 5/47 (10.6%) | 3/48 (6.3%) | ||
Limitations/Caveats
The study had been prematurely terminated by the sponsor because positive results were obtained in another Nexavar trial (Phase 3 study 100554 NCT00105443). NCI-CTC was translated to MedDRA for SOCs only.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The institution of the Coordinating Investigator (CI) has the right, consistent with academic standards, to publish any proposed publication written by the consultant as part of their services under this agreement. If the sponsor believes that any proposed publication contained any confidential information, the sponsor shall notify the CI, and the CI shall remove such confidential information.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | BAYER |
| Phone | |
| clinical-trials-contact@bayerhealthcare.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00108953
Other Study ID Numbers:
- 11546
- 2004-001770-40
First Posted:
Apr 22, 2005
Last Update Posted:
Oct 31, 2014
Last Verified:
Oct 1, 2014