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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00678392




Registration number
NCT00678392
Ethics application status
Date submitted
12/05/2008
Date registered
15/05/2008
Date last updated
9/01/2019

Titles & IDs
Public title
Axitinib (AG 013736) As Second Line Therapy For Metastatic Renal Cell Cancer
Scientific title
AXITINIB (AG-013736) AS SECOND LINE THERAPY FOR METASTATIC RENAL CELL CANCER: AXIS TRIAL
Secondary ID [1] 0 0
AXIS TRIAL
Secondary ID [2] 0 0
A4061032
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Axitinib (AG-013736)
Treatment: Drugs - Sorafenib

Experimental: Axitinib -

Active comparator: Sorafenib -


Treatment: Drugs: Axitinib (AG-013736)
axitinib will be given at a starting dose of 5 mg twice daily \[BID\] with continuous dosing

Treatment: Drugs: Sorafenib
sorafenib will be given at a dose of 400 mg twice daily \[BID\] with continuous dosing
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [3] 0 0
Duration of Response (DR)
Timepoint [3] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [4] 0 0
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [4] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [5] 0 0
Percentage of Participants With Adverse Events (AEs) by Severity
Timepoint [5] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [6] 0 0
Percentage of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [6] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [7] 0 0
Number of Participants With Clinically Significant Laboratory Abnormalities: Hematology
Timepoint [7] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [8] 0 0
Number of Participants With Clinically Significant Laboratory Abnormalities: Biochemistry
Timepoint [8] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [9] 0 0
Number of Participants With Clinically Significant Laboratory Abnormalities: Urinalysis
Timepoint [9] 0 0
From initiation of treatment up to follow-up period (up to 3 years)
Secondary outcome [10] 0 0
Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15) Score
Timepoint [10] 0 0
Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)
Secondary outcome [11] 0 0
Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Score
Timepoint [11] 0 0
Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)
Secondary outcome [12] 0 0
Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Health State Profile Utility Score
Timepoint [12] 0 0
Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)
Secondary outcome [13] 0 0
Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Visual Analog Scale (VAS)
Timepoint [13] 0 0
Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/09/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/02/2016
Sample size
Target
Accrual to date
Final
723
Recruitment in Australia
Recruitment state(s)
ACT,SA,VIC
Recruitment hospital [1] 0 0
The Canberra Hospital, Medical Oncology - Garran
Recruitment hospital [2] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [3] 0 0
Ballarat Oncology & Haematology Services - Ballarat
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [5] 0 0
Heidelberg Repatriation Hospital, Austin Health - Heidelberg West
Recruitment hospital [6] 0 0
Austin Hospital, Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [3] 0 0
3350 - Ballarat
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment outside Australia
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United States of America
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California
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Colorado
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District of Columbia
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Indiana
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Tennessee
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Wien
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RS
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New Brunswick
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Newfoundland and Labrador
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Ontario
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P.R.
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Essen
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Hannover
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Germany
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Mainz
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Germany
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Muenchen
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Germany
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Oldenburg
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Greece
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Attiki
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Greece
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Macedonia
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India
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Haryana
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India
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Kerala
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India
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Maharashtra
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India
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Punjab
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India
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Rajasthan
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Ireland
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Dublin 24
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Arezzo
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Aviano (PN)
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Brescia
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Napoli
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Pavia
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Roma
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Rozzano (MI)
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Ibaraki
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Chiba
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Fukuoka
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Tokushima
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Yamagata
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Korea, Republic of
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Gyeonggi-do
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Busan
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Wroclaw
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Russian Federation
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Singapore
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Bratislava
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Zilina
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Spain
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Barcelona
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Navarra
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Madrid
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Malaga
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Sevilla
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Spain
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Zaragoza
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Sweden
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Linkoping
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Sweden
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Umea
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Sweden
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Vaxjo
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Taiwan
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Kaohsiung Hsien
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Taiwan
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Taichung
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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United Kingdom
State/province [116] 0 0
England
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United Kingdom
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Middlesex
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United Kingdom
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Bebington, Wirral
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United Kingdom
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Birmingham
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United Kingdom
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Bournemouth
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United Kingdom
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Bristol
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United Kingdom
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Cambridge
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United Kingdom
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Glasgow
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United Kingdom
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London
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United Kingdom
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Oxford
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United Kingdom
State/province [126] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00678392
Trial related presentations / publications
Murphy DA, Rini BI, Escudier B, Motzer RJ, Wang P, Li S, Williams JA, Tarazi JC, Martini JF. Angiogenic and immunomodulatory biomarkers in axitinib-treated patients with advanced renal cell carcinoma. Future Oncol. 2020 Jun;16(17):1199-1210. doi: 10.2217/fon-2020-0212. Epub 2020 May 4.
Bracarda S, Bamias A, Casper J, Negrier S, Sella A, Staehler M, Tarazi J, Felici A, Rosbrook B, Jardinaud-Lopez M, Escudier B. Is Axitinib Still a Valid Option for mRCC in the Second-Line Setting? Prognostic Factor Analyses From the AXIS Trial. Clin Genitourin Cancer. 2019 Jun;17(3):e689-e703. doi: 10.1016/j.clgc.2019.03.017. Epub 2019 Apr 1.
de Velasco G, McKay RR, Lin X, Moreira RB, Simantov R, Choueiri TK. Comprehensive Analysis of Survival Outcomes in Non-Clear Cell Renal Cell Carcinoma Patients Treated in Clinical Trials. Clin Genitourin Cancer. 2017 Dec;15(6):652-660.e1. doi: 10.1016/j.clgc.2017.03.004. Epub 2017 Mar 21.
Grunwald V, Lin X, Kalanovic D, Simantov R. Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26.
Grunwald V, McKay RR, Krajewski KM, Kalanovic D, Lin X, Perkins JJ, Simantov R, Choueiri TK. Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol. 2015 May;67(5):952-8. doi: 10.1016/j.eururo.2014.12.036. Epub 2015 Jan 7.
Escudier B, Michaelson MD, Motzer RJ, Hutson TE, Clark JI, Lim HY, Porfiri E, Zalewski P, Kannourakis G, Staehler M, Tarazi J, Rosbrook B, Cisar L, Hariharan S, Kim S, Rini BI. Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomised phase III trial. Br J Cancer. 2014 Jun 10;110(12):2821-8. doi: 10.1038/bjc.2014.244. Epub 2014 May 13.
Ueda T, Uemura H, Tomita Y, Tsukamoto T, Kanayama H, Shinohara N, Tarazi J, Chen C, Kim S, Ozono S, Naito S, Akaza H. Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from the global randomized Phase 3 AXIS trial. Jpn J Clin Oncol. 2013 Jun;43(6):616-28. doi: 10.1093/jjco/hyt054. Epub 2013 Apr 28.
Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. doi: 10.1016/S1470-2045(13)70093-7. Epub 2013 Apr 16. Erratum In: Lancet Oncol. 2013 Jun;14(7):e254.
Cella D, Escudier B, Rini B, Chen C, Bhattacharyya H, Tarazi J, Rosbrook B, Kim S, Motzer R. Patient-reported outcomes for axitinib vs sorafenib in metastatic renal cell carcinoma: phase III (AXIS) trial. Br J Cancer. 2013 Apr 30;108(8):1571-8. doi: 10.1038/bjc.2013.145. Epub 2013 Apr 11.
Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. doi: 10.1016/S0140-6736(11)61613-9. Epub 2011 Nov 4. Erratum In: Lancet. 2012 Nov 24;380(9856):1818.
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00678392