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Axitinib (AG 013736) As Second Line Therapy For Metastatic Renal Cell Cancer

Primary Purpose

Kidney Neoplasms

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Axitinib (AG-013736)

Sorafenib

About this trial

This is an interventional treatment trial for Kidney Neoplasms focused on measuring Axitinib in Second Line Treatment of Patients With Metastatic Renal Cell Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically or cytologically confirmed renal cell cancer with a component of clear cell subtype, with metastasis
Evidence of measurable disease
Must have failed one prior systemic first-line regimen for metastatic renal cell cancer

Exclusion Criteria:

Prior treatment for metastatic renal cell cancer with more that one systemic first line therapy
Major surgery less than 4 weeks or radiation less than 2 weeks of starting study drug

Sites / Locations

East Valley Hematology and Oncology Medical Group
Maurice Berkowtiz, MD
Agajanian Institute of Oncology and Hematology
Los Angeles Hematology/Oncology Medical Group
Los Angeles Hematology/Oncology Medical Group
LAC-USC Medical Center
USC Norris Cancer Hospital and Clinics
Kenmar Research Institute
Metropolitan Hematology/Oncology Medical Group
Ronald Regan UCLA Medical Center
UCLA
Agajanian Institute of Oncology and Hematology
Brian LeBerthon, MD, A Medical Corporation
Agajanian Institute of Oncology and Hematology
Rocky Mountain Cancer Centers
University of Colorado Cancer Center
University of Colorado Denver: Division of Medical Oncology
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers, LLP
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Georgetown University Hospital, Lombardi Cancer Center
Georgetown University Medical Center
Florida Cancer Specialists
Florida Cancer Specialists
Florida Cancer Specialists
Florida Cancer Specialists
University of Miami Sylvester at Deerfield Beach
Florida Cancer Specialists
Florida Cancer Specialists
Florida Cancer Specialists
Florida Cancer Specialists
Florida Cancer Specialists
University of Miami Hospital and Clinics
Florida Cancer Specialists
Florida Cancer Specialists
M.D. Anderson Cancer Center Orlando
Orlando Regional Medical Center
Florida Cancer Specialists
Florida Cancer Specialists
Florida Cancer Specialists
Florida Cancer Specialists
Florida Cancer Specialists
Peachtree Hematology-Oncology Consultants, P.C.
Chattanooga Oncology and Hematology Associates, PC
Mountain States Tumor Institute
Mountain States Tumor Institute
Mountain States Tumor Institute
Mountain States Tumor Institute
Mountain States Tumor Institute
Loyola University Chicago Cardinal Bernardin Cancer Center
Cental Indiana Cancer Centers
Central Indiana Cancer Centers
Cental Indiana Cancer Centers
Central Indiana Cancer Centers
Central Indiana Cancer Centers
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
University of Michigan Health System
Karmanos Cancer Institute
Weisberg Cancer Treatment Center
University of Minnesota Medical Center Fairview
Missouri Cancer Associates
St. John's Mercy Medical Center
St. John's Mercy, David C. Pratt Cancer Center
St. John's Mercy Medical Center
Comprehensive Cancer Centers of Nevada
Comprehensive Cancer Centers of Nevada
Nevada Cancer Institute
Comprehensive Cancer Centers of Nevada
Comprehensive Cancer Centers of Nevada
Hackensack University Medical Center
The Cancer Center at Hackensack University Medical Center - The Hillcrest Building
The Cancer Center at Hackensack University Medical Center
Montefiore Medical Center
Memorial Sloan Kettering Cancer Center - Sidney Kimmel Center
Memorial Sloan Kettering Cancer Center
Department of Medicine MSG @ SUNY HSC @ Syrcacuse, Inc.
Department of Medicine MSG @ SUNY HSC @ Syracuse, Inc.
Suny Upstate Medical University
Department of Medicine MSG @ SUNY HSC @ Syracuse, Inc
Raleigh Hematology Oncology Associates, DBA
Duke University Medical Center
Investigational Chemotherapy Services
Albermarie Hospitals
Virginia Oncology Associates
Raleigh Hematology Oncology Associates, P.C.
Case Western Reserve University
Cleveland Clinic Foundation
Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Ohio State University
James Care in Kenny
Monarch
Lake University - Ireland Cancer Center (LUICC)
UHHS - Chagrin Highlands
UHHS - Westlake
Oncology Associates of Oregon, P.C.
Willamette Valley Cancer Institute and Research Center
Penn State Milton S. Hershey Medical Center
Fox Chase Cancer Center
Medical University of South Carolina
Cancer Centers of the Carolinas
Cancer Centers of the Carolinas
Hematology and Oncology Associates of SC, LLC - Eastside Medical Center
Cancer Centers of the Carolinas, Seneca
Cancer Centers of the Carolinas
Chattanooga Oncology and Hematology Associates, PC
Chattanooga Oncology Hematology Associates P.C.
Tennessee Oncology, PLLC
Vanderbilt-Ingram Cancer Center-Cool Springs
Tennessee Oncology, PLLC
Tennessee Oncology, PLLC
Chattanooga Oncology & Hematology Associates
Tennessee Oncology, PLLC
Tennessee Oncology, PLLC
Sarah Cannon Research Institute
Tennessee Oncology, PLLC
Tennessee Oncology, PLLC
Tennessee Oncology, PLLC
Tennessee Oncology, PLLC
Vanderbilt-Ingram Cancer Center
Vanderbilt University Medical Center
Tennessee Oncology, PLLC
Texas Oncology - Austin Midtown
Texas Oncology - Central Midtown
Texas Oncology - Austin Central
Texas Oncology - South Austin
Texas Oncolgoy - Austin North
Texas Oncology - Austin Northwest
Texas Oncology, P.A.
Texas Oncology - Cedar Park
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Investigation Products Center (IPC)
Investigational Products Center (IPC)
US Oncology Research and Clinical Pharmacy
Genitourinary Cancer Center
The University of Texas MD Anderson Cancer Center
Texas Oncology - Seton Williamson
Texas Oncology - Round Rock
Texas Oncology, P.A.
Deke Slayton Cancer Center
Texas Oncology - Clear Lake
Virginia Cancer Specialists, PC
Virginia Oncology Associates
Virginia Cancer Specialists, PC
Virginia Cancer Specialists, PC
Virginia Oncology Associates
Virginia Cancer Specialists, PC
Virginia Oncology Associates
Virginia Oncology Associates
Virginia Oncology Associates
Virginia Cancer Specialists, PC
Virginia Mason Medical Center, Section of Hematology/Oncology
Seattle Cancer Care Alliance
University of Washington Medical Center
The Canberra Hospital, Medical Oncology
Ashford Cancer Centre Research
Ballarat Oncology & Haematology Services
Peter MacCallum Cancer Centre
Heidelberg Repatriation Hospital, Austin Health
Austin Hospital, Austin Health
Med. Abt. KH Barmherzige Brueder Wien, Krankenhaus der Barmherzigen Brueder Wien
Universitaets-Klinik fuer Innere Medizin I
Clinica Oncologistas Associados
Irmandade da Santa Casa de Misericordia de Porto Alegre (ISCMPA) - Hospital Santa Rita
Fundacao Pio XII Hospital de Cancer de Barretos
Fundacao Antonio Prudente
Tom Baker Cancer Centre
Cross Cancer Institute
British Columbia Cancer Agency - Cancer Centre for the Southern Interior
Dr. Leon Richard Oncology Centre
Dr. H. Bliss Murphy Cancer Centre
RSM Durham Regional Cancer Centre Lakeridge Health Oshawa
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
The Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital
Beijing Cancer Hospital
Xijing Hospital, The Fourth Military Medical University
Sun Yet-Sen University Cancer Center
Urology Department, Renji Hospital,Shanghai Jiao Tong University School of Medicine
Tianjin Oncology Hospital,biology treatment department
Centre Leon Berard
Hopital Saint-André
Hôpital Henri Mondor
Institut Paoli-Calmettes
Hopital Europeen Georges Pompidou
Centre Eugene Marquis
Centre Rene Gauducheau - Service Oncologie Medicale
CHRU de Tours - Hopital Bretonneau
Centre Alexis Vautrin
Institut Gustave Roussy / Service d'Immunotherapie
RWTH Aachen, Urologische Klinik
Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
Innere Klinik und Poliklinik fuer Tumorforschung, Universitaetsklinikum Essen
Klinikum Region Hannover Krankenhaus Siloah
Klinikum der Johannes-Gutenberg-Universitaet, III. Medizinische Klinik und Poliklinik
Ludwig-Maximilians-Universitaet Muenchen, Klinikum Grosshadern Urologische Klinik und Poliklinik
Klinikum Oldenburg gGmbH, Klinik fuer Innere Medizin II Onkologie / Haematologie
Alexandra University Hospital / Oncology Dept.
"Theagenio"Cancer Hospital / 3rd. Dept. of Clinical Oncology
Fortis Memorial Research Institute
Amrita Institute of Medical Sciences
Dept. of Medical Oncology, Tata Memorial Hospital
Christian Medical College & Hospital
Bhagwan Mahaveer Cancer Hospital and Research Center
Oncology Department
UOC Oncologia Medica, Ospedale San Donato
Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS
Dipartimento dei laboratori diagnositici e per le terapie cellulari
Azienda Ospedaliera Spedali Civili di Brescia, Unita' Operativa Oncologia Medica
Struttura Complessa di Oncologia
UOC Oncologia Medica B, IRCCS AO Universitaria San Martino
Fondazione IRCCS, Istituto Nazionale dei Tumori, SC Oncologia Medica 2
Divisione di Oncologia, AORN Antonio Cardarelli
Istituto per lo Studio e la Cura dei Tumori Fondazione Pascale
Unita' Operativa Oncologia Medica 2, Regione del Veneto
IRCCS Policlinico San Matteo
Struttura Complessa di Oncologia Medica A
Azienda Ospedaliera San Camillo Forlanini, Oncologia Medica, Padiglione Flajani, I piano
UO di Oncologia ed Ematologia, Istituto Clinico Humanitas
Sapporo Medical University School of Medicine
Hokkaido University Hospital
University of Tsukuba, Graduate School of Comprehensive Human Sciences, Department of Urology
Kinki University Hospital
Hamamatsu University School of Medicine
Shizuoka Cancer Center
Tokyo Women's Medical University Medical Center East, Department of Urology
National Cancer Center Hospital
Nihon University Itabashi Hospital
Keio University Hospital
Tokyo Women's Medical University Hospital
Yamaguchi University Hospital
Akita University Hospital
Chiba Cancer Center
Kyushu University Hospital
Kumamoto University Hospital
Tokushima University
Yamagata University Hospital
National Cancer Center, Urologic Oncology Clinic, Center for Specific Organs Cancer
Dong-A University Medical Center, Department of Medicine, Division of Hemato-Oncology
Seoul National University Hospital
Severance Hospital
Samsung Medical Center
Catholic University of Korea, Seoul St. Mary's Hospital, Department of Oncology
Centrum Medyczne HCP
Wielkopolskie Centrum Onkologii im.Marii Sklodowskiej-Curie
Wojewodzkie Centrum Onkologii
Klinika Onkologii, Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego
Pracownia Tomografii Komputerowej
Klinika Onkologii, Wojskowy Instytut Medyczny
Klinika Urologii i Onkologii Urologicznej
Medical Radiology Research Center of the Minzdravsotsrazvitiya of Russia
Cancer Research Center named after N.N. Blokhin, Biotherapy Department
Cancer Research Center named after N.N.Blokhin, Chemotherapy Department
Russian Research Center of Roentgenology and Radiology
The Main Clinical Hospital of the Ministry of Internal Affairs of Russian Federation
Moscow Research Institute of Oncology P.A. Herzen
City Clinical Oncology Dispensary
National Cancer Centre Singapore
Onkologicky Ustav sv. Alzbety
Narodny Onkologicky ustav
Nemocnica s poliklinikou Zilina
Institut Catala D'Oncologia L'Hospitalet
Clinica Universitaria de Navarra
Hospital de Navarra
Hospital Vall D¿Hebron
Hospital Universitario Ramon Y Cajal
Hospital Universitario 12 de Octubre
Hospital Clinico Universitario Virgen de La Victoria
Hospital Universitario Virgen Macarena
Hospital Universitario Miguel Servet
Universitetssjukhuset, Onkologiska kliniken
Norrlands Universitetssjukhus, Onkologkliniken
Onkologkliniken
Chang Gung Medical Foundation-Kaohsiung Branch
Taichung Veterans General Hospital, Department of Surgery
Department of Oncology, National Taiwan University Hospital
Chang Gung Medical Foundation-Linkou Branch
Royal Marsden Hospital
Mount Vernon Cancer Centre
Clatterbridge Centre for Oncology NHS Foundation Trust
University of Birmingham, CRUK Institute for Cancer Studies
Royal Bournemouth & Poole Hospitals
Bristol Haematology and Oncology Centre
Addenbrooke's Hospital
The Beatson West of Scotland Cancer Centre
Department of Medical Oncology, St. Bartholomew's Hospital
University Department of Medical Oncology/Oxford Cancer Centre
Royal Marsden Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Axitinib

Sorafenib

Arm Description

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)

PFS was defined as the time in months from start of study treatment to the first documentation of objective tumor progression of disease (PD) or to death due to any cause, whichever occurs first. PD was assessed by response evaluation criteria in solid tumors (RECIST) version 1.0. PD: >=20 percent (%) increase in the sum of the longest dimensions (LD) of the target lesions taking as a reference the smallest sum of the LD recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. Occurrence of a pleural effusion or ascites was also considered PD if demonstrated by cytological investigation and it was not previously documented. New bone lesions not previously documented were considered PD if confirmed by computed tomography/magnetic resonance imaging or X-ray.

Secondary Outcome Measures

Overall Survival (OS)

OS was defined as the duration from start of study treatment to date of death due to any cause. OS was calculated as (months) = (date of death minus the date of first dose of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored on last date the participants were known to be alive.

Objective Response Rate (ORR)

ORR = percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0 recorded from first dose of study treatment until PD or death due to any cause. CR: disappearance of all target, non target lesions and no appearance of new lesions, documented on 2 occasions separated by at least 4 weeks. PR: at least 30 % decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non target lesions, no appearance of new lesions. PD: >=20% increase in sum of LD of the target lesions taking as a reference smallest sum of LD recorded since the start of treatment or unequivocal progression in non-target lesions or appearance of 1 or more new lesions. Occurrence of pleural effusion or ascites if demonstrated by cytological investigation, not previously documented. New bone lesions not previously documented if confirmed by computed tomography/magnetic resonance imaging or X-ray.

Duration of Response (DR)

DR: time from 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 occurred first as per RECIST version 1.0, a) CR: disappearance of all target, non target lesions and no appearance of new lesions, documented on 2 occasions separated by at least 4 weeks, b) PR: at least 30 % decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non target lesions, no appearance of new lesions, c) PD: >=20% increase in sum of LD of the target lesions taking as a reference smallest sum of LD recorded since the start of treatment or unequivocal progression in non-target lesions or appearance of 1 or more new lesions. Occurrence of pleural effusion or ascites if demonstrated by cytological investigation, not previously documented. New bone lesions not previously documented if confirmed by computed tomography/magnetic resonance imaging or X-ray.

Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.

Percentage of Participants With Adverse Events (AEs) by Severity

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 1= mild; Grade 2= moderate; Grade 3= severe; Grade 4= life-threatening or disabling; Grade 5= death related to AE.

Percentage of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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. AEs included both serious and non -serious AEs.

Number of Participants With Clinically Significant Laboratory Abnormalities: Hematology

Hematology laboratory test included hemoglobin, platelet count, white blood cells count, neutrophils and lymphocytes. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

Number of Participants With Clinically Significant Laboratory Abnormalities: Biochemistry

Biochemistry laboratory test included parameters: alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bicarbonate, bilirubin, creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, hypophosphatemia and lipase. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

Number of Participants With Clinically Significant Laboratory Abnormalities: Urinalysis

Urinalysis included urine blood/ hemoglobin, glucose and protein. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15) Score

FKSI was used to assess quality of life (QoL) for those diagnosed with renal cell cancer and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher scores indicate greater presence of symptoms.

Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Score

FKSI-DRS was used to assess quality of life for those diagnosed with renal cell cancer and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptoms) to 36 (very much); higher scores indicate greater presence of symptoms.

Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Health State Profile Utility Score

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility or index score. Health state profile component assesses level of health for 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain was rated on a 3-point response scale (1= no problems, 2= some/moderate problems and 3= extreme problems). Scoring formula developed by EuroQol Group assigned a utility value for each domain in the profile. Score were transformed and resulted in a total score range of 0 to 1, with higher scores indicating better health.

Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Visual Analog Scale (VAS)

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. VAS component: participants rated their current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health.

Full Information

NCT ID

NCT00678392

First Posted

May 12, 2008

Last Updated

December 20, 2018

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00678392

Brief Title

Axitinib (AG 013736) As Second Line Therapy For Metastatic Renal Cell Cancer

Official Title

AXITINIB (AG-013736) AS SECOND LINE THERAPY FOR METASTATIC RENAL CELL CANCER: AXIS TRIAL

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Completed

Study Start Date

September 3, 2008 (Actual)

Primary Completion Date

August 31, 2010 (Actual)

Study Completion Date

February 25, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The study is designed to demonstrate that axitinib (AG-013736) is superior to sorafenib in delaying tumor progression in patients with metastatic renal cell cancer after failure of one first line regimen.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kidney Neoplasms

Keywords

Axitinib in Second Line Treatment of Patients With Metastatic Renal Cell Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

723 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Axitinib

Arm Type

Experimental

Arm Title

Sorafenib

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Axitinib (AG-013736)

Intervention Description

axitinib will be given at a starting dose of 5 mg twice daily [BID] with continuous dosing

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Intervention Description

sorafenib will be given at a dose of 400 mg twice daily [BID] with continuous dosing

Primary Outcome Measure Information:

Title

Progression-Free Survival (PFS)

Description

Time Frame