Axitinib For The Treatment Of Advanced Hepatocellular Carcinoma

A MULTICENTER, GLOBAL, RANDOMIZED, DOUBLE-BLIND STUDY OF AXITINIB PLUS BEST SUPPORTIVE CARE VERSUS PLACEBO PLUS BEST SUPPORTIVE CARE IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA FOLLOWING FAILURE OF ONE PRIOR ANTIANGIOGENIC THERAPY

The study is designed to demonstrate that axitinib plus best supportive care is superior to placebo plus best supportive care in prolonging survival in patients with advanced hepatocellular carcinoma.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Other: Best Supportive Care; Drug: Axitinib (AG-013736); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Liège, Belgium, 4000
    • CHC Clinique Saint-Joseph
• China
  • Beijing, China, 100071
    • The PLA 307 Hospital
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital
  • Jiangsu
    • Nan Jing, Jiangsu, China, 210002
      • Nanjing Bayi Hospital
    • Nanjing, Jiangsu, China, 210009
      • Jiang Su Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University
• France
  • Amiens, France, 80054
    • Centre Hospitalier Universitaire d'Amiens
  • Bordeaux Cedex, France, 33075
    • Hopital Saint André
  • Caen, cedex 05, France, 14033
    • CHU côte de Nacre
  • Clichy, France, 92118
    • Bichat-Beaujon Service Inter Hospitalier De Cancerologie
  • Lyon Cedex 04, France, 69317
    • Hopital de la Croix-Rousse
  • Marseille, France, 13005
    • UPCET-CIC Timone
  • Montpellier Cedex 05, France, 34295
    • CHRU Montpellier-Hopital Saint Eloi - Departement Oncologie Medicale
  • Nice, France, 06200
    • Hopital L'Archet II
  • Paris, France, 75012
    • Hopital Saint Antoine
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Toulouse Cedex, France, 31059
    • CHRU de Purpan.
• Germany
  • Berlin, Germany, 13353
    • Medizinische Klinik mit Schwerpunkt
  • Bonn, Germany, 53105
    • Universitatsklinikum Bonn
  • München, Germany, 81377
    • Klinikum der Ludwig-Maximilians-Universitaet , Campus Grosshadern
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Shatin, N.T., Hong Kong
    • Prince of Wales Hospital
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem I.sz. Belgyógyászati Klinika
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem Onkoterapias Klinika
• Italy
  • Bologna, Italy, 40138
    • Istituto di Ematologia ed Oncologia Medica, Lorenzo ed Ariosto Seragnoli,
  • Bologna, Italy, 40138
    • Policlinico S.Orsola-Malpighi Dipartimento di Ematologia e Scienze Oncologiche "L. E A. Seragnoli"
  • Lido Di Camaiore (LU), Italy, 55043
    • Ospedale Versilia,Oncologia Medica
  • Meldola (FC), Italy, 47014
    • Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
  • Pavia, Italy, 27100
    • Unita Operativa Oncologia Medica IRCCS Fondazione Salvatore Maugeri
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 00168
    • Unità Operativa Oncologica Medica
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria aile Scotte
• Japan
  • Kofu-Shi, Japan, 400-8506
    • Yamanashi Prefectural Central Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Central Hospital, Diagnostic and Interventional Radiology
  • Chiba
    • Chiba City, Chiba, Japan, 260-0858
      • Chiba University Hospital
  • Gifu
    • Gifu-shi, Gifu, Japan, 5008513
      • Gifu Municipal Hospital
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital
  • Osaka
    • Osaka-Sayama, Osaka, Japan, 589-8511
      • Kinki University Hospital
  • Shizuoka
    • Suntou-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Chiyoda-Ku, Tokyo, Japan, 1010062
      • Sasaki Foundation Kyoundo Hospital
    • Itabashi-Ku, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 410-769
    • National Cancer Center/ Center for Liver Cancer
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center, Division of Hematology-Oncology, Department of Medicine
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center, Division of Oncology, Department of Internal Medicine
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna Nemocnica s Poliklinikou F. D. Roosevelta Banska Bystrica
  • Bratislava, Slovakia, 833 10
    • Narodny onkologicky ustav
  • Poprad, Slovakia, 058 01
    • POKO Poprad s.r.o.
  • Poprad, Slovakia, 058 45
    • Nemocnica Poprad, a.s.
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung, Taiwan, 833
    • Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Tainan, Taiwan, 736
    • Chi-Mei Medical Center LiouYing
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation Linkou Branch
• United Kingdom
  • Liverpool, United Kingdom, L6 7BA
    • Clatterbridge Centre for Oncology NHS Foundation Trust
  • Liverpool, United Kingdom, L69 3GA
    • Royal Liverpool and Broadgreen University Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, W12 OHS
    • Hammersmith Hospital
  • Manchester
    • Withington, Manchester, United Kingdom, M20 9BX
      • The Christie NHS Foundation Trust
• United States
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Comprehensive Cancer Center
    • La Jolla, California, United States, 92093
      • Moores UCSD Cancer Center
    • La Jolla, California, United States, 92037
      • UCSD Medical Center- La Jolla
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • San Diego, California, United States, 92103
      • UCSD Medical Center- Hillcrest
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Transplant Center, Liver Unit
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center & Research Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 86169
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89119
      • Comprehensive Cancer Centers of Nevada
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Locally advanced or metastatic HCC
• Failure of one prior antiangiogenic therapy including sorafenib, bevacizumab and brivanib.
• Child-Pugh Class A or B (score 7 only) disease.

Exclusion Criteria:

• Prior treatment of advanced HCC with more than one prior first-line systemic therapy.
• Any prior local therapy within 2 weeks of starting the study treatment.
• Presence of hepatic encephalopathy and/or clinically relevant ascites.
• Presence of main portal vein invasion by HCC.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Participants in this group received axitinib + best supportive care. Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the randomized portion at a starting axitinib dose of 5 mg BID orally. Participants with Child-Pugh Class B disease (score 7) were to begin enrollment into the randomized portion of the study following determination of the recommended axitinib starting dose in the non-randomized portion. Study treatment was administered in cycles of 4 weeks in duration	Other: Best Supportive Care; BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life.; Drug: Axitinib (AG-013736); Axitinib [tablet, 1 mg, 5 mg] will be given twice daily [BID] with continuous dosing; duration is approximately 3-6 months; starting dose is 5 mg BID
Placebo Comparator: B; Participants in this group received placebo + best supportive care. Treatment was administered in cycles of 4 weeks in duration. The starting dose of placebo for participants with Child Pugh Class A disease (score 5 or 6) was chosen as 5 mg BID. Participants with Child-Pugh Class B, score 7 received placebo that was determined from the non-randomized portion of the study until the recommended starting dose was determined, participants with Child-Pugh Class B, score 7, were not permitted to enter the randomized portion of the study	Other: Best Supportive Care; BSC may include medications and supportive measures deemed necessary to palliate disease related symptoms and improve quality of life.; Drug: Placebo; Placebo [tablet, 1 mg, 5 mg] will be given twice daily [BID] with continuous dosing; duration is approximately 3-6 months; starting dose is 5 mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) - Stratified Analysis, Randomized Portion	OS was defined as the time from the date of randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - first randomization date +1)/30.4. For participants still alive at the time of the analysis, the OS time was censored on the last date they were known to be alive. All participants were followed up for survival at least every 3 months after discontinuing study treatment until at least two years after randomization of the last participant.	From randomization until at least two years after the last participant has been randomized (up to 6 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) - Stratified Analysis, Randomized Portion	PFS was defined as time from randomization to first documented objective tumor progression or to death due to any cause, whichever occurred first. PFS (in months) was calculated as (first event date - first randomization date +1)/30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was death). As per response evaluation criteria in solid tumors (RECIST) 1.1, progression was defined as greater than or equal to (>=) 20% increase in sum of longest dimensions of target lesions or appearance of one or more new target lesions and unequivocal progression of existing non-target lesions, or appearance of 1 new non-target lesions. Participants discontinuing study treatment without documented evidence of PD were to be followed up at least every 8 weeks after discontinuing study treatment until disease progression, or initiation of another anticancer treatment.	Every 8 weeks until disease progression/death or start of new treatment or until at least two years after the last participant has been randomized, whatever occurs first
Objective Response Rate (ORR) - Percentage of Participants With Objective Response by Stratified Analysis, Randomized Portion	ORR was defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to the RECIST 1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis <10 millimetres [mm]). PR was defined as a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	Every 8 weeks until at least two years after the last participant has been randomized
Time to Tumor Progression (TTP) - Stratified Analysis, Randomized Portion	TTP was defined as the time from randomization to first documentation of objective tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in months) was calculated as (first event date - first randomization date +1)/30.4.	Every 8 weeks until disease progression/death or start of new treatment or until at least two years after the last participant has been randomized, whatever occurs first
Duration of Response (DR) by Unstratified Analysis, Randomized Portion	DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of PD or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date was to be used. DR (in months) was to be calculated as (the end date for DR - first CR or PR that was subsequently confirmed +1)/30.4.	From objective response to date of progression or death
Percentage of Participants With Overall Clinical Benefit Response (CBR) - Stratified Analysis, Randomized Portion	CBR was defined as the percentage of participants with confirmed CR or confirmed PR or a best response of stable disease >=8 weeks according to RECIST 1.1 criteria, relative to all randomized participants who had baseline measurable disease. Confirmed responses were defined as those that persisted on repeat imaging study >=4 weeks after the initial documentation of response. Participants who did not have on study radiographic tumor re-evaluation or who died, progressed, or dropped out for any reason prior to reaching a CR, PR, or stable disease were counted as non-responders in the assessment of CBR. A participant who initially met the criteria for a PR and then subsequently became a confirmed CR was to be assigned a best response of CR.	From Baseline up to end of treatment
Axitinib Steady-State Pharmacokinetic (PK) Parameter - Maximum Observed Plasma Concentration (Cmax), Non-Randomized Portion	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing.	Cycle 1 Day 15
Axitinib Steady-State PK Parameter - Area Under the Plasma Concentration Versus Time Curve From 0 to 24 Hour (AUC0-24), Non-Randomized Portion	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing. In the below table, 4 participants in Child-Pugh A and 1 participant in Child-Pugh B were not reported due to nonestimable half-life.	Cycle 1 Day 15
Axitinib Steady-State Pharmacokinetic Parameter - Time to First Occurrence of Cmax (Tmax), Non-Randomized Portion	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing.	Cycle 1 Day 15
Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Clearance (CL/F), Non-Randomized Portion	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing. In the below table, 4 participants in Child-Pugh A and 1 participant in Child-Pugh B were not reported due to nonestimable half-life.	Cycle 1 Day 15
Axitinib Steady-State Pharmacokinetic Parameter - Terminal Plasma Elimination Half-Life (t1/2), Non-Randomized Portion	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing. In the below table, 4 participants in Child-Pugh A and 1 participant in Child-Pugh B were not reported due to nonestimable half-life.	Cycle 1 Day 15
Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Volume of Distribution of the Drug During the Elimination Phase (Vz/F), Non-Randomized Portion	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing. The PK parameter, Vz/F has been presented in this outcome measure. In the below table, 4 participants in Child-Pugh A and 1 participant in Child-Pugh B were not reported due to nonestimable half-life.	Cycle 1 Day 15
Concentration of Soluble Proteins at Baseline in Randomized Portion	Plasma soluble proteins interleukin-6 (IL-6), E-Selectin, interleukin-8 (IL-8), hepatocyte growth factor (HGF), matrix metalloproteinase-2 (MMP-2), stem cell factor (SCF), angiopoietin-2 (Ang-2), vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor-C (VEGF-C), soluble vascular endothelial growth factor receptor 2 (sVEGFR2), soluble vascular endothelial growth factor receptor 3 (sVEGFR3), stromal cell-derived factor-1 (SDF1), neutrophil gelatinase-associated lipocalin (NGAL), migration inhibitory factor (MIF), c-MET, regulated upon activation normal T cell expressed and presumably secreted (RANTES), and monocyte chemotactic protein-3 (MCP-3) were only measured in randomized participants.	Baseline
Percentage of Participants With Specific Micro-Ribonucleic Acid (miRNA) Transcript Present in Circulation in Randomized Portion	A 5 millilitres (mL) whole blood sample was collected from all randomized participants to evaluate the miRNA transcripts.	Baseline
Functional Assessment of Cancer Therapy - Hepatobiliary Questionnaire (FACT-Hep) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	FACT-Hep consists of 27-item FACT-G, and 18-item Hepatobiliary Subscale. FACT-Hep questionnaire uses 5-point Likert rating scale, range '0'-not at all to '4'. FACT-Hep total score ranges from 0 to 180, where highest score represents maximum achievable quality of life. Domains of FACT-G include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB) and Functional Well-Being (FWB). Hepatobiliary disease specific items include: swelling or cramps, losing weight, gastrointestinal (GI)-related questions, lack of energy, side effects, pain, fatigue, usual activities, jaundice, fevers, itching, taste of food and chills. Eight of the items (pain, back pain, stomach pain/discomfort, lack of energy, fatigue, nausea, weight loss and jaundice) make up FACT-Hepatobiliary Symptom Index (FHSI-8), and are considered to be symptoms specific to hepatobiliary cancer. Table below included mixed effect model estimated average based on all observed values/time points.	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date
Functional Assessment of Cancer Therapy - General (FACT-G) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate QoL in cancer population. FACT-G consisted of 27 questions grouped in 4 domains of general Health-Related QoL (HRQoL): PWB, SWB, EWB and FWB; each ranging from 0 (not at all) to 4 (very much). FACT-G ranged between 0 and 108. Since questions could be reversed coded, as appropriate, before calculating FACT-G, 0 and 108 could be considered worst and best health states. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date
Functional Assessment of Cancer Therapy (FACT)-Hepatobiliary Symptom Index-8 (FHSI-8) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	The FACT-Hep includes the FACT-G and a hepatobiliary module. The hepatobiliary disease specific items include: swelling or cramps, losing weight, GI related questions, lack of energy, side effects, pain, fatigue, usual activities, jaundice, fevers, itching, taste of food and chills. Eight of the items (pain, back pain, stomach pain/discomfort, lack of energy, fatigue, nausea, weight loss, and jaundice) make up the FHSI-8, and are considered to be symptoms specific to hepatobiliary cancer. FHSI-8 total score ranges from 0 to 32 where "0" is a severely symptomatic participant and the highest score indicates an asymptomatic participant. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date
Functional Assessment of Cancer Therapy-G (FACT-G) Subscales in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate QoL in cancer population. FACT-G consisted of 27 questions grouped in 4 domains of general HRQoL: PWB, SWB, EWB and FWB. Each of the individual subscale, except EWB has 7 items and each integer scored 0 to 4 making a maximum possible score of 28 (range 0 to 28). EWB has 6 items and each integer scored 0 to 4 making a maximum possible score of 24 (range 0 to 24). For all the 4 scales, higher values correspond to better health. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date
Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Subscale (FACT Hep-CS18) Questionnaire in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	This subscale consists of 18 items rated on a scale from '0' - not at all to '4' - very much regarding how much each item was present in the last 7 days. FACT-Hep-CS18 total score ranges from 0 to 72. The higher score reflects better QoL or fewer symptoms. The 18 items of this scale are associated with hepatocellular carcinoma. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date
Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Trial Outcome Index (FACT Hep-TOI) Questionnaire in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	The trial outcome index is defined to be the sum (PWB+FWB+HepCS), making it 32 items altogether. Each ranges from '0' - not at all to '4' - very much regarding how much each item was present in the last 7 days. FACT Hep -TOI total score ranges from 0 to 128, where the highest score represents a maximum achievable quality of life. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date
Time to Deterioration (TTD) Based on the Composite Endpoint in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	TTD analysis was performed for FHSI-8. Time to deterioration was defined as the time between date of randomization and date of the event.	From randomization to death or tumor progression or FHSI-8 mean score decrease >=3 points, whichever comes first
EuroQoL (EQ-5D)- Health State Profile Utility Score in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date
EuroQoL Visual Analogue Scale (EQ-VAS) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	EQ-5D VAS in rates the participant's overall health status using values from 0 (worst imaginable) to 100 (best imaginable). The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date
Number of Participants With Dose-Limiting Toxicities (DLTs) in Non-Randomized Portion	Number of Child-Pugh Class B (score 7) participants with DLT was evaluated during Cycle 1 of treatment in the non-randomized portion of the study.	Cycle 1 (4 weeks)
Number of Participants With Treatment-Emergent Adverse Events (AEs) in Non-Randomized Portion	An AE was an untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. The grade of an AE was determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.	Up to 28 days after last dose of study drug (up to 6 years)
Number of Participants With Treatment-Related Adverse Events (AEs) in Non-Randomized Portion	Treatment-related AE was any untoward medical occurrence in a participant with causal relationship to the study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The grade of an AE was determined according to CTCAE Version 3.0.	Up to 28 days after last dose of study drug (up to 6 years)
Number of Participants With Treatment-Emergent Adverse Events (AEs) in Randomized Portion	An AE was an untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes: death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. The grade of an AE was determined according to CTCAE Version 3.0.	Up to 28 days after last dose of study drug (up to 6 years)
Number of Participants With Treatment-Related Adverse Events (AEs) in Randomized Portion	Treatment-related AE was any untoward medical occurrence in a participant with causal relationship to the study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The grade of an AE was determined according to CTCAE Version 3.0.	Up to 28 days after last dose of study drug (up to 6 years)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Kang YK, Yau T, Park JW, Lim HY, Lee TY, Obi S, Chan SL, Qin S, Kim RD, Casey M, Chen C, Bhattacharyya H, Williams JA, Valota O, Chakrabarti D, Kudo M. Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma. Ann Oncol. 2015 Dec;26(12):2457-63. doi: 10.1093/annonc/mdv388. Epub 2015 Sep 18.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2010
• Primary Completion (Actual): March 3, 2014
• Study Completion (Actual): December 20, 2016

Study Registration Dates

• First Submitted: September 22, 2010
• First Submitted That Met QC Criteria: September 27, 2010
• First Posted (Estimate): September 28, 2010

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: A4061058; 2010-021590-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.