Clinical trial NCT00835978: Axitinib (AG-013736) With Or Without Dose Titration (Increase) In Patients With Kidney Cancer
Official title: Randomized, Double-blind Phase 2 Study Of Axitinib (Ag-013736) With Or Without Dose Titration In Patients With Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Renal Cell
Keywords: axitinib or AG-013736 dose titration (increase) renal cell carcinoma
kidney cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-02-04
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: Axitinib dose titration (giving a higher dose of the drug above its standard starting dose) among certain patients may improve the response to treatment.


Eligibility criteria: Inclusion Criteria:

* metastatic renal cell carcinoma (kidney cancer) with clear cell component
* no prior systemic therapy (including no prior adjuvant or neoadjuvant)
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
* Blood Pressure \< or = 140/90mmHg

Exclusion Criteria:

* brain/CNS metastasis
* using more than 2 blood pressure medications

Primary outcomes:
measure: Objective Response Rate (ORR) - Percentage of Participants With Objective Response
timeFrame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.
measure: Duration of Response (DR)
timeFrame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks
measure: Overall Survival (OS)
timeFrame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.
measure: Maximum Observed Plasma Concentration (Cmax) of Axitinib
timeFrame: Cycle 2 Day 15 (C2D15): pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib,
timeFrame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Axitinib
timeFrame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
measure: Area Under the Curve From Time Zero to 24 Hours[AUC(0-24)] for Axitinib
timeFrame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
measure: Plasma Decay Half-Life (t1/2) for Axitinib
timeFrame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
measure: Apparent Oral Clearance (CL/F) of Axitinib
timeFrame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
measure: Apparent Volume of Distribution During the Elimination Phase (Vz/F) for Axitinib
timeFrame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
measure: Change From Baseline in Systolic Blood Pressure
timeFrame: At screening (D-14 to D-1); lead-in period: Cycle 1 - Day 1 and Day 15; Cycle 2 - Day 1 and Day 15; Cycle 3 & subsequent cycles Day 1; end of study and follow-up 28 days after last dose.
measure: Change From Baseline in Diastolic Blood Pressure
timeFrame: At screening (D-14 to D-1); lead-in period: Cycle 1 - Day 1 and Day 15; Cycle 2 - Day 1 and Day 15; Cycle 3 & subsequent cycles Day 1; end of study and follow-up 28 days after last dose.
measure: Comparison of Circulating Endothelial Cells (CECs) in Blood: Cluster of Differentiation (CD)146+/CD105+ at Baseline
timeFrame: At baseline - Beginning of the lead-in period (Cycle 1 Day 1)
measure: Comparison of the Ratio of CECs in Blood: CD146+/CD105+ at Each Time Point to Baseline
timeFrame: At end of the lead-in period (Cycle 1 Day 15), Cycle 2 Day 15 and End of therapy (EOT)
measure: Circulating Endothelial Cells (CECs) in Blood: CD31+/CD146+
timeFrame: At baseline - Beginning of the lead-in period (Cycle 1 Day 1)
measure: Comparison of Ratio of CECs in Blood: CD31+/CD146+ at Each Time Point to Baseline
timeFrame: At end of the lead-in period (Cycle 1 Day 15), Cycle 2 Day 15 and End of therapy (EOT)
measure: ORR in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms
timeFrame: At baseline - Beginning of the lead-in period (Cycle 1 Day 1)
measure: PFS in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms
timeFrame: At baseline - Beginning of the lead-in period (Cycle 1 Day 1)
Other outcomes:
Locations:
city: Antioch
country: United States
facility: East Bay Medical Oncology/Hematology Medical Associates Inc.
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Pleasant Hill
country: United States
facility: Bay Area Cancer Research Group, LLC
state: California
city: Pleasant Hill
country: United States
facility: Diablo Valley Oncology and Hematology Medical Group Inc
state: California
city: Pleasant Hill
country: United States
facility: East Bay Medical Oncology/Hematology Medical Associates Inc
state: California
city: San Leandro
country: United States
facility: East Bay Medical Oncology/Hematology Medical Associates Inc
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Drug Services, IUHSCC
state: Indiana
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Cincinnati
country: United States
facility: The University Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University, James Cancer Hospital
state: Ohio
city: Columbus
country: United States
facility: JamesCare in Kenny
state: Ohio
city: West Chester
country: United States
facility: West Chester Hospital Medical Building
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Dallas
country: United States
facility: Texas Oncology, Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
state: CZE
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc Onkologicka klinika
city: Praha 8
country: Czechia
facility: Fakultni nemocnice Na Bulovce
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni, a.s. - Masarykova nemocnice V Usti nad Labem, o.z.
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Frankfurt
country: Germany
facility: Klinikum der J. W. Goethe-Universitaet, Medizinische Klinik II
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Abt. Haematologie, Haemostaseologie & Onkologie
city: Tuebingen
country: Germany
facility: Eberhardt-Karls-Universitaet Tuebingen, Klinik fuer Urologie
city: Weiden
country: Germany
facility: Klinikum Weiden Klinik fuer Urologie, Andrologie und Kinderurologie
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Osakasayama
country: Japan
facility: Kinki University Hospital
state: Osaka
city: Hamamatsu-City
country: Japan
facility: Hamamatsu University School of Medicine, University Hospital
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center
state: Tokyo
city: Koto-ku
country: Japan
facility: Japanese Foundation For Cancer Research Cancer Institute Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Akita
country: Japan
facility: Akita University Hospital
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Obninsk
country: Russian Federation
facility: Medical Radiology Research Center of the Minzdravsotsrazvitiya of Russia
state: Kaluga Region
city: Poselok Kuzmolovskiy
country: Russian Federation
facility: State Healthcare Institution "Leningrad Regional Oncology Dispensary"
state: Vsevolozhskiy Region, Leningradskaya Oblast
city: Moscow
country: Russian Federation
facility: FSBSI "N.N. Blokhin Russian Cancer Research Center"
city: Moscow
country: Russian Federation
facility: FSBI"Russian Scientific Center of Roengenoradiology" of the MH of RF
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg's State Healthcare Institution 'City Clinical Oncology Dispensary'
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg's State Healthcare Institution 'City Clinical Oncology Dispensary'
city: Samara
country: Russian Federation
facility: GBUZ "Samara Regional Clinical Oncology Dispensary"
city: Madrid
country: Spain
facility: Hospital de La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Tomita Y, Uemura H, Oya M, Shinohara N, Habuchi T, Fujii Y, Kamei Y, Umeyama Y, Bair AH, Rini BI. Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study. BMC Cancer. 2019 Jan 7;19(1):17. doi: 10.1186/s12885-018-5224-6.
citation: 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.
citation: 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.
citation: Rini BI, Melichar B, Ueda T, Grunwald V, Fishman MN, Arranz JA, Bair AH, Pithavala YK, Andrews GI, Pavlov D, Kim S, Jonasch E. Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial. Lancet Oncol. 2013 Nov;14(12):1233-42. doi: 10.1016/S1470-2045(13)70464-9. Epub 2013 Oct 18.