Sorafenib as Adjuvant Treatment in the Prevention Of Recurrence of Hepatocellular Carcinoma (STORM)
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT00692770
Collaborator
(none)
1,114
199
2
75.4
5.6
0.1
Study Details
Study Description
Brief Summary
To evaluate efficacy and safety of sorafenib versus placebo in the adjuvant treatment of Hepatocellular Carcinoma (HCC) after potentially curative treatment (surgical resection or local ablation).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1114 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized, Double-blind, Placebo-controlled Study of Sorafenib as Adjuvant Treatment for Hepatocellular Carcinoma After Surgical Resection or Local Ablation.
Actual Study Start Date
:
Aug 15, 2008
Actual Primary Completion Date
:
Nov 29, 2013
Actual Study Completion Date
:
Nov 28, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sorafenib (Nexavar, BAY43-9006) Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) |
Drug: Nexavar (Sorafenib, BAY43-9006)
Sorafenib 400 mg twice daily (BID)
|
| Placebo Comparator: Placebo Participants received 2 tablets of placebo orally twice daily (BID) |
Drug: Placebo
Placebo 2 tablets twice daily (BID)
|
Outcome Measures
Primary Outcome Measures
- Recurrence Free Survival (RFS) by Independent Assessment [From randomization up to 4 years or until disease recurrence whichever came first]
Disease recurrence of HCC (intra or extra hepatic) was defined as the appearance of a new intrahepatic lesions fulfilling the American Association for the Study of Liver Diseases (AASLD) criteria of diagnosis of HCC or a new extra-hepatic lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. In addition to investigator assessment, all images were reviewed by an independent panel of radiologists. The calculation of the RFS was based on the independent evaluation of the scans. RFS was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment or death due to any cause whichever occurred first. For subjects who had not recurred or died at the time of analysis, RFS was censored at their last date of evaluable scan before drop-out for any other reason than recurrence or death.
Secondary Outcome Measures
- Time to Recurrence (TTR) by Independent Assessment [From randomization up to 4 years or until disease recurrence whichever came first]
TTR was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment. For subjects who had not recurred at the time of analysis, TTR was censored at their last date of evaluable scan before withdrawal for any other reason than recurrence. "NA" in the reported data indicates values could not be estimated due to censored data.
- Overall Survival (OS) [From randomization of the first subject until 4 years later.]
OS was defined as the time from randomization to date of death due to any cause. OS for subjects alive at the time of analysis was censored at their last date of contact. "NA" in the reported data indicates values could not be estimated due to censored data.
Other Outcome Measures
- Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Index Score [Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit]
The EQ-5D is a generic quality of life preference based on a validated instrument used in cancer and in general population, with 2 parts: Index and Visual Analogue Scale. The EQ-5D Index is a descriptive system of the following health dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. Subjects were asked to choose any one of the 3 response levels for each dimension: no problems, some problems, and severe problems. The 5 health dimensions were summarized into a single score, the EQ-5D Index score which ranged from -0.59 to 1 with higher scores representing better health states (0=death, 1= perfect health, and -0.59=a health state worse than death). A change of at least 0.10 to 0.12 points was considered a minimally important difference using Eastern Cooperative Oncology Group Performance Status as the anchor. The results on the Analysis of covariance of timeadjusted Area under curve for the EQ-5D index score were reported.
- Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Visual Analogue Scale (VAS) Score [Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit]
The EQ-5D is a generic quality of life preference based on a validated instrument used in cancer and in general population, with 2 parts: Index and Visual Analogue Scale. The EQ-5D VAS is a measure that represents health status as a single value. It is a 20-centimetre vertical graduated visual analogue scale with scores that ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). The respondent rated his/her current health state by drawing a line from the box marked 'your own health state today' to the appropriate point on the EQ-5D VAS. A 3-digit number (including leading zeros) was read off the scale from the point where the respondent's line crossed the scale, which was the EQ-5D VAS score. A change of at least 7 points on the VAS was considered as minimally important. The results on the ANCOVA analysis of time-adjusted AUC for the EQ-5D VAS score were reported.
- Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- Hepatobiliary Subscale (HEP) Score [Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit]
The FACT-HEP is a 45 item, self-administered, multi-dimensional, psychometrically sound questionnaire used extensively in oncology clinical trials. FACT-HEP consisted of five subscales: Physical Well-Being (PWB), Social Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and Hepatobiliary Cancer Subscale (HCS). The PWB, FWB, SWB and EWB were summed to form the FACTGeneral (FACT-G) total score. The FACT-G and HCS scores were summed to form the FACT-HEP total score. FACT-HEP scores ranged from 0 to 180 and the higher scores represented a better quality of life. Subjects responded to each item on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). The minimally important difference (MID) for the FACT-Hep total score was in the range of 8 to 9. The results on the ANCOVA analysis of time-adjusted AUC for the FACT-HEP score were reported.
- Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- General (G) Total Score [Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit]
The PWB, FWB, SWB and EWB were summed to form the FACT-G total score. Subjects responded to each item on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). FACT-G scores ranged from 0 to 108 and the higher scores represented a better quality of life. The MID for the FACT-G total score was in the range of 6 to 7. The results on the ANCOVA analysis of time-adjusted AUC for the FACT-G score were reported.
- The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - ANG-2 [At Baseline]
Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only.
- The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - AFP [At Baseline]
Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only.
- The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - MET [At Baseline]
Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Subjects who have undergone surgical resection or local ablation (PEI or percutaneous or intraoperative RFA) for treatment of HCC with curative intent within 4 months from staging to potentially curative treatment. A maximum of 2 local ablation courses may be administered during this time period.
-
At least 3 weeks (21 days) but no more than 7 weeks (49 days), from resection or last local ablation course, to CT/MRI scan date
-
Male or female subjects >/= 18 years of age
-
Confirmation of CR (absence of residual tumor after curative treatment), on the eligibility scan by independent radiological review.
-
For subjects undergoing surgical resection pathology proven complete removal of tumor.
-
Intermediate or High Risk of recurrence as assessed by tumor characteristics.
-
Child-Pugh score 5 -7 points. A Child-Pugh score of 7 points is allowed only in the absence of ascites.
-
ECOG Performance Status of 0.
-
Adequate bone marrow, liver and renal function
Exclusion Criteria:
-
Recurrent HCC
-
Child-Pugh score 7 points with presence of ascites.
-
Low risk of recurrence after curative treatment
-
History of cardiovascular disease
-
History of HIV infection
-
Active clinically serious infections (> grade 2 NCI-CTCAE version 3.0)
-
Subjects with seizure disorder requiring medication (such as steroids or anti-epileptics)
-
Subjects with evidence or history of bleeding diathesis
-
Subjects undergoing renal dialysis
-
Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry as defined by the signing of informed consent..
-
Uncontrolled ascites (defined as not easily controlled with diuretic treatment)
-
Encephalopathy
-
History of GI bleeding within 30 days of randomization.
-
Subjects with a history of esophageal varices bleeding which has not been followed by effective therapy and/or treatment to prevent bleeding recurrence.
-
Prior anti cancer therapy for treatment of HCC (including sorafenib or any other molecular therapy) is excluded.
-
Major surgery within 4 weeks of start of study as defined by the signing of informed consent, except for surgical resection or local ablation of HCC.
-
Investigational drug therapy outside of this trial during or within 4 weeks of study entry, as defined by the signing of informed consent.
-
Liver transplantation, this includes patients on a transplant list with the intention to transplant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | 35294-3300 | |
| 2 | Phoenix | Arizona | United States | 85054 | |
| 3 | Los Angeles | California | United States | 90033 | |
| 4 | Los Angeles | California | United States | 90095-7077 | |
| 5 | San Francisco | California | United States | 94115 | |
| 6 | Washington | District of Columbia | United States | 20007 | |
| 7 | Miami | Florida | United States | 33136 | |
| 8 | Atlanta | Georgia | United States | 30322 | |
| 9 | Indianapolis | Indiana | United States | 46202 | |
| 10 | Louisville | Kentucky | United States | 40202 | |
| 11 | New Orleans | Louisiana | United States | 70112 | |
| 12 | Baltimore | Maryland | United States | 21287 | |
| 13 | Boston | Massachusetts | United States | 02114 | |
| 14 | Boston | Massachusetts | United States | 02215 | |
| 15 | Burlington | Massachusetts | United States | 01805 | |
| 16 | Ann Arbor | Michigan | United States | 48109 | |
| 17 | Minneapolis | Minnesota | United States | 55407 | |
| 18 | Minneapolis | Minnesota | United States | 55455 | |
| 19 | New York | New York | United States | 10029 | |
| 20 | Cleveland | Ohio | United States | 44106 | |
| 21 | Cleveland | Ohio | United States | 44195 | |
| 22 | Columbus | Ohio | United States | 43210 | |
| 23 | Providence Portland Medical Center | Portland | Oregon | United States | 97213 |
| 24 | Portland | Oregon | United States | 97239 | |
| 25 | Pittsburgh | Pennsylvania | United States | 15213 | |
| 26 | Houston | Texas | United States | 77030 | |
| 27 | Richmond | Virginia | United States | 23249 | |
| 28 | Seattle | Washington | United States | 98101 | |
| 29 | Seattle | Washington | United States | 98109 | |
| 30 | Pilar | Buenos Aires | Argentina | B1629ODT | |
| 31 | Buenos Aires | Ciudad Auton. De Buenos Aires | Argentina | C1181ACH | |
| 32 | Rosario | Santa Fe | Argentina | S2002KDS | |
| 33 | Camperdown | New South Wales | Australia | 2050 | |
| 34 | Randwick | New South Wales | Australia | 2031 | |
| 35 | Brisbane | Queensland | Australia | 4120 | |
| 36 | Heidelberg | Victoria | Australia | 3084 | |
| 37 | Melbourne | Victoria | Australia | 3004 | |
| 38 | Innsbruck | Austria | 6020 | ||
| 39 | Linz | Austria | 4020 | ||
| 40 | Wien | Austria | 1090 | ||
| 41 | Bruxelles - Brussel | Belgium | 1200 | ||
| 42 | Gent | Belgium | 9000 | ||
| 43 | Leuven | Belgium | 3000 | ||
| 44 | Liege | Belgium | 4000 | ||
| 45 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 | |
| 46 | Porto Alegre | Rio Grande Do Sul | Brazil | 90470 340 | |
| 47 | Porto Alegre | Rio Grande Do Sul | Brazil | 90610-000 | |
| 48 | São Paulo | Sao Paulo | Brazil | 01323-001 | |
| 49 | Sao Paulo | Brazil | 01246-903 | ||
| 50 | Plovdiv | Bulgaria | 4002 | ||
| 51 | Varna | Bulgaria | 2010 | ||
| 52 | Calgary | Alberta | Canada | T2N 4N1 | |
| 53 | Edmonton | Alberta | Canada | T6G 1Z2 | |
| 54 | Vancouver | British Columbia | Canada | V5Z 4E6 | |
| 55 | Ottawa | Ontario | Canada | K1H 8L6 | |
| 56 | Toronto | Ontario | Canada | M5G 2M9 | |
| 57 | Santiago de Chile | Santiago | Chile | 833-0024 | |
| 58 | Reñaca | Valparaíso | Chile | ||
| 59 | Guangzhou | Guangdong | China | 510060 | |
| 60 | Guangzhou | Guangdong | China | 510080 | |
| 61 | Guangzhou | Guangdong | China | 510515 | |
| 62 | Nanning | Guangxi | China | 530021 | |
| 63 | Wuhan | Hubei | China | 430022 | |
| 64 | Changsha | Hunan | China | 410008 | |
| 65 | Changsha | Hunan | China | 410013 | |
| 66 | Nanjing | Jiangsu | China | 210002 | |
| 67 | Xi'an | Shanxi | China | 710038 | |
| 68 | Xi'an | Shanxi | China | 710061 | |
| 69 | Xi'an | Shanxi | China | 710068 | |
| 70 | Chengdu | Sichuan | China | 610041 | |
| 71 | Chengdu | Sichuan | China | 610072 | |
| 72 | Beijing | China | 100021 | ||
| 73 | Beijing | China | 100071 | ||
| 74 | Beijing | China | 100142 | ||
| 75 | Beijing | China | 100853 | ||
| 76 | Beijng | China | 100142 | ||
| 77 | Chongqing | China | 400038 | ||
| 78 | Dalian | China | 116027 | ||
| 79 | Hefei | China | 230022 | ||
| 80 | Shanghai | China | 200001 | ||
| 81 | Shanghai | China | 200438 | ||
| 82 | Tianjin | China | 300060 | ||
| 83 | ANGERS cedex 09 | France | 49933 | ||
| 84 | Bondy | France | 93143 | ||
| 85 | Bordeaux | France | 33000 | ||
| 86 | Creteil | France | 94010 | ||
| 87 | Lille | France | 59037 | ||
| 88 | Lyon | France | 69004 | ||
| 89 | Marseille | France | 13005 | ||
| 90 | Nice | France | 06202 | ||
| 91 | Paris | France | 75020 | ||
| 92 | Paris | France | 75571 | ||
| 93 | Rennes | France | 35000 | ||
| 94 | Toulouse | France | 31059 | ||
| 95 | Vandoeuvre-les-nancy | France | 54500 | ||
| 96 | Villejuif | France | 94800 | ||
| 97 | München | Bayern | Germany | 81377 | |
| 98 | München | Bayern | Germany | 81675 | |
| 99 | Regensburg | Bayern | Germany | 93042 | |
| 100 | Göttingen | Niedersachsen | Germany | 37075 | |
| 101 | Hannover | Niedersachsen | Germany | 30625 | |
| 102 | Aachen | Nordrhein-Westfalen | Germany | 52074 | |
| 103 | Düsseldorf | Nordrhein-Westfalen | Germany | 40225 | |
| 104 | Essen | Nordrhein-Westfalen | Germany | 45147 | |
| 105 | Köln | Nordrhein-Westfalen | Germany | 50937 | |
| 106 | Mainz | Rheinland-Pfalz | Germany | 55131 | |
| 107 | Homburg/Saar | Saarland | Germany | 66421 | |
| 108 | Halle/Saale | Sachsen-Anhalt | Germany | 06120 | |
| 109 | Magdeburg | Sachsen-Anhalt | Germany | 39120 | |
| 110 | Berlin | Germany | 12200 | ||
| 111 | Hamburg | Germany | 20246 | ||
| 112 | Athens / Greece | Greece | 115 27 | ||
| 113 | Hong Kong | Hong Kong | |||
| 114 | Kwun Tong | Hong Kong | |||
| 115 | Shatin | Hong Kong | |||
| 116 | Benevento | Campania | Italy | 82100 | |
| 117 | Napoli | Campania | Italy | 80123 | |
| 118 | Napoli | Campania | Italy | 80131 | |
| 119 | Bologna | Emilia-Romagna | Italy | 40138 | |
| 120 | Modena | Emilia-Romagna | Italy | 41124 | |
| 121 | Roma | Lazio | Italy | 00168 | |
| 122 | Milano | Lombardia | Italy | 20121 | |
| 123 | Milano | Lombardia | Italy | 20133 | |
| 124 | Torino | Piemonte | Italy | 10126 | |
| 125 | Bari | Puglia | Italy | 70124 | |
| 126 | Cagliari | Sardegna | Italy | 09134 | |
| 127 | Catania | Sicilia | Italy | 95122 | |
| 128 | Palermo | Sicilia | Italy | 90127 | |
| 129 | Padova | Veneto | Italy | 35128 | |
| 130 | Kashiwa-shi | Chiba | Japan | 277-8577 | |
| 131 | Kanazawa | Ishikawa | Japan | 920-8641 | |
| 132 | Yokohama-shi | Kanagawa | Japan | 232-0024 | |
| 133 | Osakasayama-shi | Osaka | Japan | 589-8511 | |
| 134 | Suita | Osaka | Japan | 565-0871 | |
| 135 | Bunkyo-ku | Tokyo | Japan | 113-8655 | |
| 136 | Chuo-ku | Tokyo | Japan | 104-0045 | |
| 137 | Itabashi-ku | Tokyo | Japan | 173-8610 | |
| 138 | Minato-ku | Tokyo | Japan | 105-8470 | |
| 139 | Shibuya-ku | Tokyo | Japan | 150-8935 | |
| 140 | Shinjuku-ku | Tokyo | Japan | 162-8666 | |
| 141 | Fukuoka | Japan | 812-8582 | ||
| 142 | Kumamoto | Japan | 860-8556 | ||
| 143 | Kyoto | Japan | 606-8507 | ||
| 144 | Okayama | Japan | 700-8558 | ||
| 145 | Osaka | Japan | 537-8511 | ||
| 146 | Tokushima | Japan | 770-8503 | ||
| 147 | Goyang-si | Gyeonggido | Korea, Republic of | 410-769 | |
| 148 | Goyang-si | Gyeonggido | Korea, Republic of | 411-706 | |
| 149 | Seoul | Seoul Teugbyeolsi | Korea, Republic of | 135-720 | |
| 150 | Busan | Korea, Republic of | 49241 | ||
| 151 | Daegu | Korea, Republic of | 700721 | ||
| 152 | Jeollabuk-do | Korea, Republic of | 561-712 | ||
| 153 | Seoul | Korea, Republic of | 05505 | ||
| 154 | Seoul | Korea, Republic of | 110-744 | ||
| 155 | Seoul | Korea, Republic of | 120-752 | ||
| 156 | Seoul | Korea, Republic of | 135-710 | ||
| 157 | México, D.F. | Distrito Federal | Mexico | 14080 | |
| 158 | Monterrey | Nuevo Leon | Mexico | 64710 | |
| 159 | México, D.F. | Mexico | 14050 | ||
| 160 | Auckland | New Zealand | 1023 | ||
| 161 | Coimbra | Portugal | 3000-075 | ||
| 162 | Bucharest | Romania | 022326 | ||
| 163 | Cluj-Napoca | Romania | 400015 | ||
| 164 | Iasi | Romania | 700106 | ||
| 165 | Moscow | Russian Federation | 115478 | ||
| 166 | Moscow | Russian Federation | 119991 | ||
| 167 | Obninsk | Russian Federation | 249036 | ||
| 168 | St. Petersburg | Russian Federation | 197758 | ||
| 169 | Singapore | Singapore | 119228 | ||
| 170 | Singapore | Singapore | 169608 | ||
| 171 | Oviedo | Asturias | Spain | 33011 | |
| 172 | Sabadell | Barcelona | Spain | 08208 | |
| 173 | Cruces/Barakaldo | Bilbao | Spain | 48903 | |
| 174 | Barcelona | Catalunya | Spain | 08035 | |
| 175 | Majadahonda | Madrid | Spain | 28222 | |
| 176 | Badajoz | Spain | 06080 | ||
| 177 | Barcelona | Spain | 08036 | ||
| 178 | Córdoba | Spain | 14004 | ||
| 179 | Madrid | Spain | 28007 | ||
| 180 | Madrid | Spain | 28040 | ||
| 181 | Valladolid | Spain | 47012 | ||
| 182 | Göteborg | Sweden | 413 45 | ||
| 183 | Stockholm | Sweden | 141 86 | ||
| 184 | Bern | Switzerland | 3010 | ||
| 185 | Zürich | Switzerland | 8091 | ||
| 186 | Changhua | Taiwan | 500-06 | ||
| 187 | Kaohsiung City | Taiwan | 807 | ||
| 188 | Kaohsung | Taiwan | 833 | ||
| 189 | Tainan | Taiwan | 704 | ||
| 190 | Taipei | Taiwan | 100 | ||
| 191 | Taipei | Taiwan | 112 | ||
| 192 | Taoyuan | Taiwan | 333 | ||
| 193 | Southampton | Hampshire | United Kingdom | SO16 6YD | |
| 194 | Birmingham | West Midlands | United Kingdom | B15 2TT | |
| 195 | Leeds | West Yorkshire | United Kingdom | LS9 7TF | |
| 196 | London | United Kingdom | NW3 2QG | ||
| 197 | London | United Kingdom | SE5 9RS | ||
| 198 | Manchester | United Kingdom | M20 4BX | ||
| 199 | Newcastle Upon Tyne | United Kingdom | NE7 7DN |
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:
NCT00692770
Other Study ID Numbers:
- 12414
- 2008-001087-36
First Posted:
Jun 6, 2008
Last Update Posted:
Aug 8, 2018
Last Verified:
Jul 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Bayer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participant recruitment period was between 15 August 2008 to 12 November 2010. |
|---|---|
| Pre-assignment Detail | Of 1602 participants who were screened for inclusion in the study, 1114 were enrolled, and 1107 received treatment. |
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo |
|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) |
| Period Title: Overall Study | ||
| STARTED | 556 | 558 |
| Participants Received Treatment | 553 | 554 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 556 | 558 |
Baseline Characteristics
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) | Total of all reporting groups |
| Overall Participants | 556 | 558 | 1114 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
58.1
(11.7)
|
58.7
(12.2)
|
58.4
(12.0)
|
| Age, Customized (Count of Participants) | |||
| <18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
383
68.9%
|
361
64.7%
|
744
66.8%
|
| >=65 years |
173
31.1%
|
197
35.3%
|
370
33.2%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
105
18.9%
|
97
17.4%
|
202
18.1%
|
| Male |
451
81.1%
|
461
82.6%
|
912
81.9%
|
Outcome Measures
| Title | Recurrence Free Survival (RFS) by Independent Assessment |
|---|---|
| Description | Disease recurrence of HCC (intra or extra hepatic) was defined as the appearance of a new intrahepatic lesions fulfilling the American Association for the Study of Liver Diseases (AASLD) criteria of diagnosis of HCC or a new extra-hepatic lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. In addition to investigator assessment, all images were reviewed by an independent panel of radiologists. The calculation of the RFS was based on the independent evaluation of the scans. RFS was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment or death due to any cause whichever occurred first. For subjects who had not recurred or died at the time of analysis, RFS was censored at their last date of evaluable scan before drop-out for any other reason than recurrence or death. |
| Time Frame | From randomization up to 4 years or until disease recurrence whichever came first |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included participants who were randomized to study treatments. |
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo |
|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) |
| Measure Participants | 556 | 558 |
| Median (95% Confidence Interval) [Days] |
1014
|
1026
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.258329 |
| Comments | One sided P-value was stratified by region, risk of recurrence and previous curative treatment. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.94 | |
| Confidence Interval |
(2-Sided) 95% 0.78 to 1.134 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Recurrence (TTR) by Independent Assessment |
|---|---|
| Description | TTR was defined as the time from randomization to the first documented disease recurrence by independent radiological assessment. For subjects who had not recurred at the time of analysis, TTR was censored at their last date of evaluable scan before withdrawal for any other reason than recurrence. "NA" in the reported data indicates values could not be estimated due to censored data. |
| Time Frame | From randomization up to 4 years or until disease recurrence whichever came first |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included participants who were randomized to study treatments. |
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo |
|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) |
| Measure Participants | 556 | 558 |
| Median (95% Confidence Interval) [Days] |
1172
|
1089
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.121383 |
| Comments | One sided P-value was stratified by region, risk of recurrence and previous curative treatment. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.891 | |
| Confidence Interval |
(2-Sided) 95% 0.735 to 1.081 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time from randomization to date of death due to any cause. OS for subjects alive at the time of analysis was censored at their last date of contact. "NA" in the reported data indicates values could not be estimated due to censored data. |
| Time Frame | From randomization of the first subject until 4 years later. |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included participants who were randomized to study treatments. |
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo |
|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) |
| Measure Participants | 556 | 558 |
| Median (95% Confidence Interval) [Days] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.484742 |
| Comments | One-sided P-value was stratified by region, risk of recurrence and previous curative treatment. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.995 | |
| Confidence Interval |
(2-Sided) 95% 0.761 to 1.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Index Score |
|---|---|
| Description | The EQ-5D is a generic quality of life preference based on a validated instrument used in cancer and in general population, with 2 parts: Index and Visual Analogue Scale. The EQ-5D Index is a descriptive system of the following health dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. Subjects were asked to choose any one of the 3 response levels for each dimension: no problems, some problems, and severe problems. The 5 health dimensions were summarized into a single score, the EQ-5D Index score which ranged from -0.59 to 1 with higher scores representing better health states (0=death, 1= perfect health, and -0.59=a health state worse than death). A change of at least 0.10 to 0.12 points was considered a minimally important difference using Eastern Cooperative Oncology Group Performance Status as the anchor. The results on the Analysis of covariance of timeadjusted Area under curve for the EQ-5D index score were reported. |
| Time Frame | Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included participants who were randomized to study treatments. |
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo |
|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) |
| Measure Participants | 556 | 558 |
| Least Squares Mean (95% Confidence Interval) [Unit on a scale] |
0.827
|
0.866
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | An analysis of covariance (ANCOVA) model was used to estimate the mean difference in the timeadjusted Area Under Curve (AUC) between the two treatment groups, with covariates for baseline scores and stratification factors. To test the treatment effect, a mixed linear model (random coefficient model) was used for the EQ-5D index score. Statistical tests were performed with a 2 sided type I error of 5%. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.039 | |
| Confidence Interval |
(2-Sided) 95% 0.025 to 0.052 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Patient Reported Outcomes: Euroqol-5 Dimensions (EQ-5D) - Visual Analogue Scale (VAS) Score |
|---|---|
| Description | The EQ-5D is a generic quality of life preference based on a validated instrument used in cancer and in general population, with 2 parts: Index and Visual Analogue Scale. The EQ-5D VAS is a measure that represents health status as a single value. It is a 20-centimetre vertical graduated visual analogue scale with scores that ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). The respondent rated his/her current health state by drawing a line from the box marked 'your own health state today' to the appropriate point on the EQ-5D VAS. A 3-digit number (including leading zeros) was read off the scale from the point where the respondent's line crossed the scale, which was the EQ-5D VAS score. A change of at least 7 points on the VAS was considered as minimally important. The results on the ANCOVA analysis of time-adjusted AUC for the EQ-5D VAS score were reported. |
| Time Frame | Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included participants who were randomized to study treatments. |
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo |
|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) |
| Measure Participants | 556 | 558 |
| Least Squares Mean (95% Confidence Interval) [Unit on a scale] |
77.203
|
80.181
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | An analysis of covariance (ANCOVA) model was used to estimate the mean difference in the timeadjusted Area Under Curve (AUC) between the two treatment groups, with covariates for baseline scores and stratification factors. To test the treatment effect, a mixed linear model (random coefficient model) was used for the EQ-5D VAS score. Statistical tests were performed with a 2 sided type I error of 5%. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.978 | |
| Confidence Interval |
(2-Sided) 95% 1.797 to 4.159 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- Hepatobiliary Subscale (HEP) Score |
|---|---|
| Description | The FACT-HEP is a 45 item, self-administered, multi-dimensional, psychometrically sound questionnaire used extensively in oncology clinical trials. FACT-HEP consisted of five subscales: Physical Well-Being (PWB), Social Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and Hepatobiliary Cancer Subscale (HCS). The PWB, FWB, SWB and EWB were summed to form the FACTGeneral (FACT-G) total score. The FACT-G and HCS scores were summed to form the FACT-HEP total score. FACT-HEP scores ranged from 0 to 180 and the higher scores represented a better quality of life. Subjects responded to each item on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). The minimally important difference (MID) for the FACT-Hep total score was in the range of 8 to 9. The results on the ANCOVA analysis of time-adjusted AUC for the FACT-HEP score were reported. |
| Time Frame | Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included participants who were randomized to study treatments. |
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo |
|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) |
| Measure Participants | 556 | 558 |
| Least Squares Mean (95% Confidence Interval) [Unit on a scale] |
138.7
|
143.79
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | An ANCOVA model was used to estimate the mean difference in the timeadjusted AUC between the two treatment groups, with covariates for baseline scores and stratification factors. To test the treatment effect, a mixed linear model (random coefficient model) was used for the FACT-HEP score. Statistical tests were performed with a 2 sided type I error of 5%. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.1 | |
| Confidence Interval |
(2-Sided) 95% 3.5 to 6.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Patient Reported Outcomes: Functional Assessment of Cancer Therapy (FACT)- General (G) Total Score |
|---|---|
| Description | The PWB, FWB, SWB and EWB were summed to form the FACT-G total score. Subjects responded to each item on a 5-point Likert-type scale ranging from 0 (not at all) to 4 (very much). FACT-G scores ranged from 0 to 108 and the higher scores represented a better quality of life. The MID for the FACT-G total score was in the range of 6 to 7. The results on the ANCOVA analysis of time-adjusted AUC for the FACT-G score were reported. |
| Time Frame | Cycle (C) Day (D)1, C2D1, C3D1 and subsequent cycles up to C18, end of intervention visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included participants who were randomized to study treatments. |
| Arm/Group Title | Sorafenib (Nexavar, BAY43-9006) | Placebo |
|---|---|---|
| Arm/Group Description | Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID) | Participants received 2 tablets of placebo orally twice daily (BID) |
| Measure Participants | 556 | 558 |
| Least Squares Mean (95% Confidence Interval) [Unit on a scale] |
80.46
|
82.95
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | An ANCOVA model was used to estimate the mean difference in the timeadjusted AUC between the two treatment groups, with covariates for baseline scores and stratification factors. To test the treatment effect, a mixed linear model (random coefficient model) was used for the FACT-G score. Statistical tests were performed with a 2 sided type I error of 5%. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.5 | |
| Confidence Interval |
(2-Sided) 95% 1.4 to 3.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - ANG-2 |
|---|---|
| Description | Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only. |
| Time Frame | At Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Plasma biomarker analysis was done in 858 (77%) of the all enrolled subjects. |
| Arm/Group Title | ANG-2 High Expression Group | ANG-2 Low Expression Group |
|---|---|---|
| Arm/Group Description | ANG-2 high expression group included participants with the ANG-2 expression higher than 4009.765 pg/mL. | ANG-2 low expression group included participants with the ANG-2 expression lower than 4009.765 pg/mL. |
| Measure Participants | 258 | 600 |
| Median (95% Confidence Interval) [Days] |
588
|
1260
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.562 | |
| Confidence Interval |
(2-Sided) 95% 1.241 to 1.965 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Significance of the biomarker main effect (RFS) and its corresponding hazard ratio estimate (HR) with 95% CI were reported. HR was expressed as high/low biomarker levels. | |
| Title | The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - AFP |
|---|---|
| Description | Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only. |
| Time Frame | At Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Plasma biomarker analysis was done in 858 (77%) of the all enrolled subjects. |
| Arm/Group Title | AFP High Expression Group | AFP Low Expression Group |
|---|---|---|
| Arm/Group Description | AFP high expression group included participants with the AFP expression higher than 3.899 ng/mL. | AFP low expression group included participants with the AFP expression lower than 3.899 ng/mL. |
| Measure Participants | 333 | 525 |
| Median (95% Confidence Interval) [Days] |
668
|
1267
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.747 | |
| Confidence Interval |
(2-Sided) 95% 1.407 to 2.170 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Significance of the biomarker main effect (RFS) and its corresponding hazard ratio estimate (HR) with 95% CI were reported. HR was expressed as high/low biomarker levels. | |
| Title | The Correlation Between Plasma Biomarker Levels at Baseline With RFS to Determine Prognostic Value of Biomarkers - MET |
|---|---|
| Description | Biomarker was analyzed at baseline [i.e., before treatment] as a dichotomized variable based on median biomarker levels, and dichotomized into "high" and "low" groups using an optimal max chi cut-off approach - not per intervention. As such, results were analyzed according to this stratification. Max-chi square methodology was used to search for the optimal cut point for dichotomization of each plasma biomarker and Kaplan-Meier curves were generated using the optimal cut point for each possible association examined. These biomarker analyses were retrospective and exploratory and of signal generating nature only. |
| Time Frame | At Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Plasma biomarker analysis was done in 858 (77%) of the all enrolled subjects. |
| Arm/Group Title | MET High Expression Group | MET Low Expression Group |
|---|---|---|
| Arm/Group Description | MET high expression group included participants with the MET expression higher than 182.444 ng/mL. | MET low expression group included participants with the MET expression lower than 182.444 ng/mL. |
| Measure Participants | 632 | 226 |
| Median (95% Confidence Interval) [Days] |
841
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sorafenib (Nexavar, BAY43-9006), Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.560 | |
| Confidence Interval |
(2-Sided) 95% 1.206 to 2.018 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Significance of the biomarker main effect (RFS) and its corresponding hazard ratio estimate (HR) with 95% CI were reported. HR was expressed as high/low biomarker levels. | |
Adverse Events
| Time Frame | From the date of signing informed consent up to 30 days post-treatment discontinuation | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | In the safety analysis set (SAF), subjects were analyzed as treated but not randomized, therefore, few subjects in the placebo group of the full analysis set were switched to the sorafenib group of the SAF. Hence, SAF for safety analyses comprised of 548 subjects in the placebo group and 559 subjects in the sorafenib group. | |||
| Arm/Group Title | Placebo | Sorafenib (Nexavar, BAY43-9006) | ||
| Arm/Group Description | Subjects received 2 tablets of placebo orally twice daily. | Subjects received 2 tablets of Sorafenib [2*200 milligram (mg)] orally twice daily. | ||
All Cause Mortality |
||||
| Placebo | Sorafenib (Nexavar, BAY43-9006) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Sorafenib (Nexavar, BAY43-9006) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 230/548 (42%) | 228/559 (40.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Neutropenia | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Pancytopenia | 0/548 (0%) | 0 | 1/559 (0.2%) | 3 |
| Bone marrow failure | 0/548 (0%) | 0 | 1/559 (0.2%) | 3 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/548 (0.2%) | 1 | 2/559 (0.4%) | 2 |
| Angina pectoris | 2/548 (0.4%) | 3 | 1/559 (0.2%) | 1 |
| Angina unstable | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Aortic valve stenosis | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Arteriosclerosis coronary artery | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Atrioventricular block complete | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Bradycardia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Cardiac failure | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Cardiac failure congestive | 0/548 (0%) | 0 | 1/559 (0.2%) | 3 |
| Coronary artery disease | 1/548 (0.2%) | 1 | 2/559 (0.4%) | 2 |
| Myocardial infarction | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Myocardial ischaemia | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 2 |
| Left ventricular dysfunction | 1/548 (0.2%) | 2 | 1/559 (0.2%) | 2 |
| Ear and labyrinth disorders | ||||
| Deafness | 0/548 (0%) | 0 | 1/559 (0.2%) | 5 |
| Tinnitus | 0/548 (0%) | 0 | 1/559 (0.2%) | 5 |
| Vertigo | 2/548 (0.4%) | 3 | 0/559 (0%) | 0 |
| Eye disorders | ||||
| Cataract | 1/548 (0.2%) | 1 | 4/559 (0.7%) | 6 |
| Retinal vein occlusion | 0/548 (0%) | 0 | 1/559 (0.2%) | 4 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/548 (0%) | 0 | 3/559 (0.5%) | 3 |
| Abdominal pain upper | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Ascites | 1/548 (0.2%) | 1 | 3/559 (0.5%) | 4 |
| Crohn's disease | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Diaphragmatic hernia, obstructive | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Diarrhoea | 2/548 (0.4%) | 3 | 2/559 (0.4%) | 2 |
| Duodenal ulcer | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Duodenitis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Enteritis | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Femoral hernia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Gastric ulcer haemorrhage | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Gastritis | 0/548 (0%) | 0 | 4/559 (0.7%) | 4 |
| Gastrointestinal haemorrhage | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Haematemesis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Impaired gastric emptying | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Inguinal hernia | 3/548 (0.5%) | 3 | 2/559 (0.4%) | 5 |
| Large intestine perforation | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Oesophageal varices haemorrhage | 0/548 (0%) | 0 | 4/559 (0.7%) | 6 |
| Pancreatitis | 1/548 (0.2%) | 2 | 2/559 (0.4%) | 2 |
| Pancreatitis acute | 2/548 (0.4%) | 2 | 1/559 (0.2%) | 1 |
| Small intestinal obstruction | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Stomatitis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Umbilical hernia | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Upper gastrointestinal haemorrhage | 2/548 (0.4%) | 2 | 0/559 (0%) | 0 |
| Gastric volvulus | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Haemorrhoidal haemorrhage | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Varices oesophageal | 2/548 (0.4%) | 3 | 2/559 (0.4%) | 2 |
| Gastric varices haemorrhage | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Abdominal hernia | 2/548 (0.4%) | 2 | 0/559 (0%) | 0 |
| Localised intraabdominal fluid collection | 1/548 (0.2%) | 5 | 0/559 (0%) | 0 |
| General disorders | ||||
| Asthenia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Chest pain | 1/548 (0.2%) | 1 | 2/559 (0.4%) | 2 |
| Death | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Drowning | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Fatigue | 0/548 (0%) | 0 | 3/559 (0.5%) | 4 |
| Multi-organ failure | 0/548 (0%) | 0 | 3/559 (0.5%) | 3 |
| Pyrexia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Sudden cardiac death | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Coronary artery restenosis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Inflammation | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Unevaluable event | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Hepatobiliary disorders | ||||
| Bile duct stone | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Biliary fistula | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Cholangitis | 2/548 (0.4%) | 2 | 0/559 (0%) | 0 |
| Cholangitis acute | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Cholecystitis | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Cholecystitis acute | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Hepatic failure | 0/548 (0%) | 0 | 1/559 (0.2%) | 3 |
| Hepatic function abnormal | 1/548 (0.2%) | 2 | 4/559 (0.7%) | 9 |
| Hepatorenal syndrome | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Jaundice cholestatic | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Portal vein thrombosis | 0/548 (0%) | 0 | 2/559 (0.4%) | 5 |
| Bile duct stenosis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Hepatic mass | 0/548 (0%) | 0 | 1/559 (0.2%) | 3 |
| Biloma | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Liver injury | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Infections and infestations | ||||
| Appendicitis | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Bacteraemia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Bronchitis | 1/548 (0.2%) | 1 | 3/559 (0.5%) | 4 |
| Cellulitis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Gastrointestinal infection | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Hepatitis B | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Hepatitis C | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Liver abscess | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Nasopharyngitis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Osteomyelitis | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Peritonitis | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Pneumonia | 1/548 (0.2%) | 1 | 2/559 (0.4%) | 2 |
| Pulmonary tuberculosis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Pyelonephritis | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 2 |
| Pyelonephritis acute | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Sepsis | 2/548 (0.4%) | 2 | 1/559 (0.2%) | 1 |
| Superinfection | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Tuberculosis | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Upper respiratory tract infection | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Urinary tract infection | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Urosepsis | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Rectal abscess | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Staphylococcal bacteraemia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Biliary sepsis | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Acute hepatitis B | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Abdominal abscess | 3/548 (0.5%) | 4 | 0/559 (0%) | 0 |
| Lung infection | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Peritonitis bacterial | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Infected dermal cyst | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Infectious pleural effusion | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Accidental overdose | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Arterial injury | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Hip fracture | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Humerus fracture | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Incisional hernia | 1/548 (0.2%) | 2 | 2/559 (0.4%) | 2 |
| Ligament sprain | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Radius fracture | 3/548 (0.5%) | 3 | 0/559 (0%) | 0 |
| Rib fracture | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Spinal compression fracture | 1/548 (0.2%) | 4 | 0/559 (0%) | 0 |
| Sternal fracture | 1/548 (0.2%) | 3 | 0/559 (0%) | 0 |
| Tibia fracture | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Ulna fracture | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Vascular injury | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Wrist fracture | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Thoracic vertebral fracture | 1/548 (0.2%) | 3 | 0/559 (0%) | 0 |
| Face injury | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Brain contusion | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Wound evisceration | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Post procedural bile leak | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Pelvic fracture | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Limb crushing injury | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Toxicity to various agents | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Aspartate aminotransferase increased | 1/548 (0.2%) | 2 | 2/559 (0.4%) | 2 |
| Lipase increased | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Liver function test abnormal | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Weight decreased | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Diabetes mellitus | 2/548 (0.4%) | 2 | 0/559 (0%) | 0 |
| Hypoalbuminaemia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Hypoglycaemia | 2/548 (0.4%) | 2 | 0/559 (0%) | 0 |
| Hypokalaemia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Decreased appetite | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Type 2 diabetes mellitus | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/548 (0.2%) | 2 | 1/559 (0.2%) | 2 |
| Bone formation increased | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Exostosis | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Gouty arthritis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Muscular weakness | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Osteoarthritis | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Rotator cuff syndrome | 1/548 (0.2%) | 16 | 0/559 (0%) | 0 |
| Intervertebral disc protrusion | 2/548 (0.4%) | 2 | 0/559 (0%) | 0 |
| Spondylolisthesis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/548 (0.2%) | 3 | 0/559 (0%) | 0 |
| Benign hepatic neoplasm | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Bladder cancer | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Breast cancer | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Chronic myeloid leukaemia | 1/548 (0.2%) | 5 | 0/559 (0%) | 0 |
| Colon cancer | 1/548 (0.2%) | 2 | 1/559 (0.2%) | 2 |
| Gastric cancer | 1/548 (0.2%) | 2 | 1/559 (0.2%) | 2 |
| Haemangioma of liver | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Hepatic neoplasm | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Laryngeal squamous cell carcinoma | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Metastases to lung | 2/548 (0.4%) | 2 | 1/559 (0.2%) | 1 |
| Metastatic pain | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Non-Hodgkin's lymphoma | 1/548 (0.2%) | 4 | 0/559 (0%) | 0 |
| Oesophageal adenocarcinoma | 1/548 (0.2%) | 4 | 0/559 (0%) | 0 |
| Pancreatic carcinoma | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Rectal adenocarcinoma | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Schwannoma | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Skin papilloma | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Squamous cell carcinoma of the hypopharynx | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Adenocarcinoma pancreas | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Lung neoplasm malignant | 2/548 (0.4%) | 4 | 4/559 (0.7%) | 8 |
| Desmoid tumour | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Prostate cancer | 1/548 (0.2%) | 3 | 0/559 (0%) | 0 |
| Hepatobiliary neoplasm | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Nasopharyngeal cancer | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Lip and/or oral cavity cancer | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Neoplasm recurrence | 2/548 (0.4%) | 2 | 0/559 (0%) | 0 |
| Lung neoplasm | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Huerthle cell carcinoma | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Oral papilloma | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Hepatocellular carcinoma | 130/548 (23.7%) | 154 | 82/559 (14.7%) | 98 |
| Nervous system disorders | ||||
| Carotid artery thrombosis | 0/548 (0%) | 0 | 1/559 (0.2%) | 4 |
| Cerebellar haemorrhage | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Cerebral haemorrhage | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Cerebral infarction | 0/548 (0%) | 0 | 2/559 (0.4%) | 4 |
| Cerebral ischaemia | 1/548 (0.2%) | 1 | 2/559 (0.4%) | 2 |
| Cerebrovascular accident | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Encephalopathy | 0/548 (0%) | 0 | 3/559 (0.5%) | 3 |
| Guillain-Barre syndrome | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Haemorrhage intracranial | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Headache | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Hepatic encephalopathy | 2/548 (0.4%) | 2 | 3/559 (0.5%) | 7 |
| Hypertensive encephalopathy | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Neuropathy peripheral | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Presyncope | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Spinal cord compression | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Spinal cord infarction | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Psychiatric disorders | ||||
| Alcohol abuse | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Alcoholism | 1/548 (0.2%) | 4 | 0/559 (0%) | 0 |
| Confusional state | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Renal and urinary disorders | ||||
| Calculus urinary | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Hydronephrosis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Nephrolithiasis | 2/548 (0.4%) | 2 | 0/559 (0%) | 0 |
| Nephrotic syndrome | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Renal colic | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Renal failure | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Renal failure acute | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Ureteric obstruction | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Urinary retention | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Diabetic nephropathy | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Dyspnoea | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Epistaxis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Haemoptysis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Interstitial lung disease | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Laryngeal oedema | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Pleural effusion | 1/548 (0.2%) | 1 | 3/559 (0.5%) | 3 |
| Pleurisy | 2/548 (0.4%) | 3 | 0/559 (0%) | 0 |
| Pneumonitis | 1/548 (0.2%) | 2 | 0/559 (0%) | 0 |
| Pneumothorax | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Pulmonary embolism | 4/548 (0.7%) | 5 | 1/559 (0.2%) | 1 |
| Pulmonary granuloma | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Pulmonary haemorrhage | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Pulmonary mass | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Sinusitis noninfective | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Angioedema | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
| Dermal cyst | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Dermatitis allergic | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Palmar-plantar erythrodysaesthesia syndrome | 1/548 (0.2%) | 1 | 10/559 (1.8%) | 11 |
| Pruritus | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Rash | 0/548 (0%) | 0 | 2/559 (0.4%) | 3 |
| Skin ulcer | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Telangiectasia | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Surgical and medical procedures | ||||
| Incisional hernia repair | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Neoplasm prophylaxis | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Removal of foreign body from gastrointestinal tract | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Vascular disorders | ||||
| Arteriovenous fistula | 1/548 (0.2%) | 1 | 0/559 (0%) | 0 |
| Hypertension | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Hypertensive crisis | 0/548 (0%) | 0 | 2/559 (0.4%) | 2 |
| Peripheral vascular disorder | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Inferior vena caval occlusion | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Peripheral embolism | 1/548 (0.2%) | 1 | 1/559 (0.2%) | 1 |
| Artery dissection | 0/548 (0%) | 0 | 1/559 (0.2%) | 1 |
| Peripheral arterial occlusive disease | 0/548 (0%) | 0 | 1/559 (0.2%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Sorafenib (Nexavar, BAY43-9006) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 360/ (NaN) | 522/ (NaN) | ||
| Blood and lymphatic system disorders | ||||
| Thrombocytopenia | 14/548 (2.6%) | 97 | 29/559 (5.2%) | 217 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 46/548 (8.4%) | 115 | 55/559 (9.8%) | 156 |
| Abdominal pain upper | 14/548 (2.6%) | 36 | 28/559 (5%) | 75 |
| Ascites | 19/548 (3.5%) | 67 | 39/559 (7%) | 145 |
| Constipation | 36/548 (6.6%) | 122 | 41/559 (7.3%) | 105 |
| Diarrhoea | 64/548 (11.7%) | 186 | 242/559 (43.3%) | 1201 |
| Dyspepsia | 30/548 (5.5%) | 125 | 20/559 (3.6%) | 112 |
| Nausea | 24/548 (4.4%) | 45 | 50/559 (8.9%) | 119 |
| General disorders | ||||
| Fatigue | 66/548 (12%) | 300 | 83/559 (14.8%) | 315 |
| Pyrexia | 24/548 (4.4%) | 32 | 33/559 (5.9%) | 39 |
| Infections and infestations | ||||
| Nasopharyngitis | 38/548 (6.9%) | 69 | 30/559 (5.4%) | 66 |
| Investigations | ||||
| Alanine aminotransferase increased | 38/548 (6.9%) | 177 | 54/559 (9.7%) | 251 |
| Aspartate aminotransferase increased | 35/548 (6.4%) | 188 | 51/559 (9.1%) | 226 |
| Platelet count decreased | 26/548 (4.7%) | 202 | 48/559 (8.6%) | 300 |
| Weight decreased | 13/548 (2.4%) | 41 | 60/559 (10.7%) | 254 |
| Weight increased | 42/548 (7.7%) | 310 | 14/559 (2.5%) | 68 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 18/548 (3.3%) | 52 | 40/559 (7.2%) | 104 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 30/548 (5.5%) | 139 | 34/559 (6.1%) | 162 |
| Back pain | 37/548 (6.8%) | 192 | 43/559 (7.7%) | 152 |
| Nervous system disorders | ||||
| Headache | 33/548 (6%) | 108 | 40/559 (7.2%) | 111 |
| Psychiatric disorders | ||||
| Insomnia | 31/548 (5.7%) | 178 | 24/559 (4.3%) | 111 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 44/548 (8%) | 116 | 30/559 (5.4%) | 76 |
| Dysphonia | 3/548 (0.5%) | 7 | 41/559 (7.3%) | 133 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 18/548 (3.3%) | 65 | 187/559 (33.5%) | 750 |
| Palmar-plantar erythrodysaesthesia syndrome | 27/548 (4.9%) | 139 | 390/559 (69.8%) | 2196 |
| Pruritus | 58/548 (10.6%) | 263 | 47/559 (8.4%) | 133 |
| Rash | 45/548 (8.2%) | 126 | 95/559 (17%) | 296 |
| Vascular disorders | ||||
| Hypertension | 65/548 (11.9%) | 331 | 142/559 (25.4%) | 869 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | BAYER |
| Phone | |
| clinical-trials-contact@bayerhealthcare.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00692770
Other Study ID Numbers:
- 12414
- 2008-001087-36
First Posted:
Jun 6, 2008
Last Update Posted:
Aug 8, 2018
Last Verified:
Jul 1, 2018