Axitinib (AG-013736) With Or Without Dose Titration (Increase) In Patients With Kidney Cancer

Carcinoma, Renal Cell Clinical Trial

Official title:

Randomized, Double-blind Phase 2 Study Of Axitinib (Ag-013736) With Or Without Dose Titration In Patients With Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00835978
• Other study ID #: A4061046
• Secondary ID: 2008-007786-23
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 2, 2009
• Last updated: December 10, 2015
• Start date: August 2009
• Est. completion date: February 2016

Study information

• Verified date: December 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 213
• Est. completion date: February 2016
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• axitinib
axitinib 5mg BID (open-label) + axitinib dose titration (blinded)
• axitinib
axitinib 5mg BID (open-label) + placebo dose titration (blinded)
• axitinib
axitinib 5mg BID (open-label)

Locations

Country	Name	City	State
Czech Republic	Masarykuv onkologicky ustav	Brno	CZE
Czech Republic	Fakultni nemocnice Olomouc Onkologicka klinika	Olomouc
Czech Republic	Fakultni nemocnice Na Bulovce	Praha 8
Czech Republic	Krajska zdravotni, a.s. - Masarykova nemocnice V Usti nad Labem, o.z.	Usti nad Labem
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Klinikum der J. W. Goethe-Universitaet, Medizinische Klinik II	Frankfurt
Germany	Medizinische Hochschule Hannover, Abt. Haematologie, Haemostaseologie & Onkologie	Hannover
Germany	Eberhardt-Karls-Universitaet Tuebingen, Klinik fuer Urologie	Tuebingen
Germany	Klinikum Weiden Klinik fuer Urologie, Andrologie und Kinderurologie	Weiden
Japan	Akita University Hospital	Akita
Japan	Chiba Cancer Center	Chiba
Japan	National Cancer Center	Chuo-ku	Tokyo
Japan	Kyushu University Hospital	Fukuoka
Japan	Hamamatsu University School of Medicine, University Hospital	Hamamatsu-City	Shizuoka
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	Japanese Foundation For Cancer Research Cancer Institute Hospital	Koto-ku	Tokyo
Japan	Nagasaki University Hospital	Nagasaki
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Kinki University Hospital	Osakasayama	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Tokushima University Hospital	Tokushima
Japan	Yamagata University Hospital	Yamagata
Russian Federation	FSBI"Russian Scientific Center of Roengenoradiology" of the MH of RF	Moscow
Russian Federation	Institution of Russian Academy of Medical Sciences	Moscow
Russian Federation	Medical Radiology Research Center of the Minzdravsotsrazvitiya of Russia	Obninsk	Kaluga region
Russian Federation	State Healthcare Institution "Leningrad Regional Oncology Dispensary"	Poselok Kuzmolovskiy	Vsevolozhskiy region, Leningradskaya oblast
Russian Federation	Saint-Petersburg's State Healthcare Institution 'City Clinical Oncology Dispensary'	Saint-Petersburg
Russian Federation	Saint-Petersburg's State Healthcare Institution 'City Clinical Oncology Dispensary'	Saint-Petersburg
Russian Federation	GBUZ "Samara Regional Clinical Oncology Dispensary"	Samara
Spain	Hospital de La Princesa	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario La Paz	Madrid
United States	East Bay Medical Oncology/Hematology Medical Associates Inc.	Antioch	California
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University Hospital	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	JamesCare in Kenny	Columbus	Ohio
United States	The Ohio State University, James Cancer Hospital	Columbus	Ohio
United States	Texas Oncology, Sammons Cancer Center	Dallas	Texas
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center- Investigational Pharmacy Services	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Investigational Drug Services, IUHSCC	Indianapolis	Indiana
United States	IU Health University Hospital	Indianapolis	Indiana
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Bay Area Cancer Research Group, LLC	Pleasant Hill	California
United States	Diablo Valley Oncology and Hematology Medical Group Inc	Pleasant Hill	California
United States	East Bay Medical Oncology/Hematology Medical Associates Inc	Pleasant Hill	California
United States	Oregon Health and Science University	Portland	Oregon
United States	East Bay Medical Oncology/Hematology Medical Associates Inc	San Leandro	California
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Barnes-Jewish Hospital	St. Louis	Missouri
United States	Washington University	St. Louis	Missouri
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	West Chester Hospital Medical Building	West Chester	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Czech Republic,  Germany,  Japan,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) - Percentage of Participants With Objective Response	ORR was defined as the proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease. No new lesions. PR was defined as >=30% decrease on study under baseline of the sum of longest diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions.	Baseline up to disease progression, death, or withdrawal with minimum follow-up of 12 months; assessments performed at baseline and repeated every 8 weeks.	No
Secondary	Objective Response Rate (ORR) - Percentage of Participants With Objective Response (All Participants)	ORR was defined as the proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease. No new lesions. PR was defined as >=30% decrease on study under baseline of the sum of longest diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions.	Baseline up to disease progression, death, or withdrawal with minimum follow-up of 12 months; assessments performed at baseline and repeated every 8 weeks.	No
Secondary	Progression-Free Survival (PFS)	The time from first dose administration to first documentation of objective tumor progression or to death due to any cause. PFS in each arm was assessed using the Kaplan-Meier method and estimates of the PFS curves from the Kaplan-Meier method were presented.	Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks	No
Secondary	Progression-Free Survival (PFS) - All Participants	The time from first dose administration to first documentation of objective tumor progression or to death due to any cause. PFS in each arm was assessed using the Kaplan-Meier method and estimates of the PFS curves from the Kaplan-Meier method were presented.	Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks	No
Secondary	Duration of Response (DR)	DR was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. The median values were estimated based on Kaplan-Meier method. 95% confidence interval was based on the Brookmeyer and Crowley method.	Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks	No
Secondary	Overall Survival (OS)	OS was defined as the time from date of the first dose of the study medication to date of death due to any cause. For participants who did not die, their survival times were to be censored at the last date they were known to be alive.	Baseline up to at least one year after the last patient has been randomized.	Yes
Secondary	Maximum Observed Plasma Concentration (Cmax) of Axitinib	Cmax for steady-state axitinib was evaluated on Cycle 2 Day 15. Results were normalized to axitinib 7 mg dose for active titration arm and axitinib 5 mg dose for placebo titration arm. Results were normalized to axitinib 7 mg dose for active titration arm and axitinib 5 mg dose for placebo titration arm.	Cycle 2 Day 15 (C2D15): pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib,	Tmax for steady-state axitinib was evaluated on Cycle 2 Day 15.	C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Axitinib	Area under the plasma concentration time-curve from zero to the last measurable concentration (AUClast). AUClast for steady-state axitinib was evaluated on Cycle 2 Day 15. Results were normalized to axitinib 7 mg dose for active titration arm and axitinib 5 mg dose for placebo titration arm.	C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose	No
Secondary	Area Under the Curve From Time Zero to 24 Hours[AUC(0-24)] for Axitinib	Area under the plasma concentration time-curve from zero 24 hours[AUC(0-24). AUC(0-24) for steady-state axitinib was evaluated on Cycle 2 Day 15. Results were normalized to axitinib 7 mg dose for active titration arm and axitinib 5 mg dose for placebo titration arm.	C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose	No
Secondary	Plasma Decay Half-Life (t1/2) for Axitinib	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half life for steady-state axitinib was evaluated on Cycle 2 Day 15.	C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose	No
Secondary	Apparent Oral Clearance (CL/F) of Axitinib	Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Clearance is defined as the volume of blood from which drug can be completely removed per unit of time. CL/F for steady-state axitinib was evaluated on Cycle 2 Day 15.	C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose	No
Secondary	Apparent Volume of Distribution During the Elimination Phase (Vz/F) for Axitinib	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz/F is influenced by the fraction absorbed. Vz/F for steady-state axitinb was evaluated on Cycle 2 Day 15.	C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose	No
Secondary	Change From Baseline in Systolic Blood Pressure	Value at respective visit minus value at baseline	Baseline up to follow-up visit	Yes
Secondary	Change From Baseline in Diastolic Blood Pressure	Value at respective visit minus value at baseline.	Baseline up to follow-up visit	Yes
Secondary	Comparison of Circulating Endothelial Cells (CECs) in Blood: Cluster of Differentiation (CD)146+/CD105+ at Baseline	CECs are noninvasive marker of vascular damage, remodeling, and dysfunction. Samples were collected and following proteins were analyzed: CD146+/CD105+ CECs, CD146+/CD105+ mean fluorescence intensity (MFI) platelet derived growth factor receptor (PDGFR)-beta, CD146+/CD105+ MFI phospho-PDGFR (pPDGFR)-beta, CD146+/CD105+ phospho-Vascular endothelial growth factor receptor (pVEGFR), CD146+/CD105+ MFI VEGFR. The ratio of plasma levels of the biomarkers at the selected time point vs baseline is reported.	Baseline	No
Secondary	Comparison of the Ratio of CECs in Blood: CD146+/CD105+ at Each Time Point to Baseline	CECs are noninvasive marker of vascular damage, remodeling, and dysfunction. Samples were collected and following proteins were analyzed: CD146+/CD105+ CECs, CD146+/CD105+ MFI platelet derived growth factor receptor (PDGFR)-beta, CD146+/CD105+ MFI phospho-PDGFR (pPDGFR)-beta, CD146+/CD105+ phospho-VEGFR (pVEGFR), CD146+/CD105+ MFI VEGFR. The ratio of plasma levels of the biomarkers at the selected time point vs baseline is reported.	Cycle 1 Day 1 (C1D1), C1D15, C2D15, End of therapy (EOT)	No
Secondary	Circulating Endothelial Cells (CECs) in Blood: CD31+/CD146+	CECs are noninvasive marker of vascular damage, remodeling, and dysfunction. Samples were collected and following proteins were analyzed: CD31+/CD146+ CECs, CD31+/CD146+ MFI PDGFR-beta, CD31+/CD146+ MFI pPDGFR-beta, CD31+/CD146+ pVEGFR, CD31+/CD146+ MFI VEGFR. The ratio of plasma levels of the biomarkers at the selected time point vs baseline is reported.	Baseline	No
Secondary	Comparison of Ratio of CECs in Blood: CD31+/CD146+ at Each Time Point to Baseline	CECs are noninvasive marker of vascular damage, remodeling, and dysfunction. Samples were collected and following proteins were analyzed: CD31+/CD146+ CECs, CD31+/CD146+ MFI PDGFR-beta, CD31+/CD146+ MFI pPDGFR-beta, CD31+/CD146+ pVEGFR, CD31+/CD146+ MFI VEGFR. The ratio of plasma levels of the biomarkers at the selected time point vs baseline is reported.	C1D1, C1D15, C2D15, EOT	No
Secondary	ORR in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms	ORR, defined as proportion of participants with CR or PR according to RECIST, in subgroups that were defined by VEGFA or VEGFR3 polymorphisms.	Baseline, C1D1	No
Secondary	PFS in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms	PFS, defined as the time from randomization to first documentation of objective tumor progression or to death due to any cause, in subgroups that were defined by VEGFA or VEGFR3 polymorphisms. Estimates of the PFS curves from the Kaplan-Meier method were presented.	Baseline, C1D1	No

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