Clinical trial NCT01210495: Axitinib For The Treatment Of Advanced Hepatocellular Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-09-28
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS) - Stratified Analysis, Randomized Portion
timeFrame: From randomization until at least two years after the last participant has been randomized (up to 6 years)
Secondary outcomes:
measure: Progression-Free Survival (PFS) - Stratified Analysis, Randomized Portion
timeFrame: 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
measure: Objective Response Rate (ORR) - Percentage of Participants With Objective Response by Stratified Analysis, Randomized Portion
timeFrame: Every 8 weeks until at least two years after the last participant has been randomized
measure: Time to Tumor Progression (TTP) - Stratified Analysis, Randomized Portion
timeFrame: 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
measure: Duration of Response (DR) by Unstratified Analysis, Randomized Portion
timeFrame: From objective response to date of progression or death
measure: Percentage of Participants With Overall Clinical Benefit Response (CBR) - Stratified Analysis, Randomized Portion
timeFrame: From Baseline up to end of treatment
measure: Axitinib Steady-State Pharmacokinetic (PK) Parameter - Maximum Observed Plasma Concentration (Cmax), Non-Randomized Portion
timeFrame: Cycle 1 Day 15
measure: Axitinib Steady-State PK Parameter - Area Under the Plasma Concentration Versus Time Curve From 0 to 24 Hour (AUC0-24), Non-Randomized Portion
timeFrame: Cycle 1 Day 15
measure: Axitinib Steady-State Pharmacokinetic Parameter - Time to First Occurrence of Cmax (Tmax), Non-Randomized Portion
timeFrame: Cycle 1 Day 15
measure: Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Clearance (CL/F), Non-Randomized Portion
timeFrame: Cycle 1 Day 15
measure: Axitinib Steady-State Pharmacokinetic Parameter - Terminal Plasma Elimination Half-Life (t1/2), Non-Randomized Portion
timeFrame: Cycle 1 Day 15
measure: Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Volume of Distribution of the Drug During the Elimination Phase (Vz/F), Non-Randomized Portion
timeFrame: Cycle 1 Day 15
measure: Concentration of Soluble Proteins at Baseline in Randomized Portion
timeFrame: Baseline
measure: Percentage of Participants With Specific Micro-Ribonucleic Acid (miRNA) Transcript Present in Circulation in Randomized Portion
timeFrame: Baseline
measure: Functional Assessment of Cancer Therapy - Hepatobiliary Questionnaire (FACT-Hep) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model
timeFrame: 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
measure: Functional Assessment of Cancer Therapy - General (FACT-G) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model
timeFrame: 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
measure: 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
timeFrame: 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
measure: Functional Assessment of Cancer Therapy-G (FACT-G) Subscales in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Time to Deterioration (TTD) Based on the Composite Endpoint in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model
timeFrame: From randomization to death or tumor progression or FHSI-8 mean score decrease >=3 points, whichever comes first
measure: EuroQoL (EQ-5D)- Health State Profile Utility Score in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model
timeFrame: 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
measure: EuroQoL Visual Analogue Scale (EQ-VAS) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model
timeFrame: 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
measure: Number of Participants With Dose-Limiting Toxicities (DLTs) in Non-Randomized Portion
timeFrame: Cycle 1 (4 weeks)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) in Non-Randomized Portion
timeFrame: Up to 28 days after last dose of study drug (up to 6 years)
measure: Number of Participants With Treatment-Related Adverse Events (AEs) in Non-Randomized Portion
timeFrame: Up to 28 days after last dose of study drug (up to 6 years)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) in Randomized Portion
timeFrame: Up to 28 days after last dose of study drug (up to 6 years)
measure: Number of Participants With Treatment-Related Adverse Events (AEs) in Randomized Portion
timeFrame: Up to 28 days after last dose of study drug (up to 6 years)
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Alta Bates Summit Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: UCSD Medical Center- La Jolla
state: California
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Diego
country: United States
facility: UCSD Medical Center- Hillcrest
state: California
city: Orlando
country: United States
facility: Florida Hospital Transplant Center, Liver Unit
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center & Research Institute
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Liège
country: Belgium
facility: CHC Clinique Saint-Joseph
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Nan Jing
country: China
facility: Nanjing Bayi Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiang Su Cancer Hospital
state: Jiangsu
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: The PLA 307 Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Amiens
country: France
facility: Centre Hospitalier Universitaire d'Amiens
city: Bordeaux Cedex
country: France
facility: Hopital Saint André
city: Caen, cedex 05
country: France
facility: CHU Cote de Nacre
city: Clichy
country: France
facility: Bichat-Beaujon Service Inter Hospitalier De Cancerologie
city: Lyon Cedex 04
country: France
facility: Hopital De La Croix-Rousse
city: Marseille
country: France
facility: UPCET-CIC Timone
city: Montpellier Cedex 05
country: France
facility: CHRU Montpellier-Hopital Saint Eloi - Departement Oncologie Medicale
city: Nice
country: France
facility: Hôpital L'Archet Ii
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Toulouse Cedex
country: France
facility: CHRU de Purpan.
city: Berlin
country: Germany
facility: Medizinische Klinik mit Schwerpunkt
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: München
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universitaet , Campus Grosshadern
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin, N.T.
country: Hong Kong
facility: Prince of Wales Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem I.sz. Belgyógyászati Klinika
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Onkoterápiás Klinika
city: Bologna
country: Italy
facility: Istituto di Ematologia ed Oncologia Medica, Lorenzo ed Ariosto Seragnoli,
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi Dipartimento di Ematologia e Scienze Oncologiche "L. E A. Seragnoli"
city: Lido Di Camaiore (LU)
country: Italy
facility: Ospedale Versilia,Oncologia Medica
city: Meldola (FC)
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori IRST
city: Pavia
country: Italy
facility: Unita Operativa Oncologia Medica IRCCS Fondazione Salvatore Maugeri
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Roma
country: Italy
facility: Unità Operativa Oncologica Medica
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria aile Scotte
city: Nagoya
country: Japan
facility: Aichi Cancer Center Central Hospital, Diagnostic and Interventional Radiology
state: Aichi
city: Chiba City
country: Japan
facility: Chiba University Hospital
state: Chiba
city: Gifu-shi
country: Japan
facility: Gifu Municipal Hospital
state: Gifu
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Osaka-Sayama
country: Japan
facility: Kinki University Hospital
state: Osaka
city: Suntou-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chiyoda-Ku
country: Japan
facility: Sasaki Foundation Kyoundo Hospital
state: Tokyo
city: Itabashi-Ku
country: Japan
facility: Nihon University Itabashi Hospital
state: Tokyo
city: Kofu-Shi
country: Japan
facility: Yamanashi Prefectural Central Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center/ Center for Liver Cancer
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center, Division of Hematology-Oncology, Department of Medicine
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Division of Oncology, Department of Internal Medicine
city: Banska Bystrica
country: Slovakia
facility: Fakultna nemocnica s poliklinikou F. D. Roosevelta Banska Bystrica
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Poprad
country: Slovakia
facility: POKO Poprad s.r.o.
city: Poprad
country: Slovakia
facility: Nemocnica Poprad, a.s.
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Center LiouYing
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation Linkou Branch
city: Withington
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Manchester
city: Liverpool
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool and Broadgreen University Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.