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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00835978
First received: February 2, 2009
Last updated: August 5, 2014
Last verified: August 2014

February 2, 2009
August 5, 2014
August 2009
October 2012   (final data collection date for primary outcome measure)
Objective Response Rate (ORR) - Percentage of Participants With Objective Response [ Time Frame: Baseline up to disease progression, death, or withdrawal with minimum follow-up of 12 months; assessments performed at baseline and repeated every 8 weeks. ] [ Designated as safety issue: No ]
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.
Overall Response Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00835978 on ClinicalTrials.gov Archive Site
  • Objective Response Rate (ORR) - Percentage of Participants With Objective Response (All Participants) [ Time Frame: Baseline up to disease progression, death, or withdrawal with minimum follow-up of 12 months; assessments performed at baseline and repeated every 8 weeks. ] [ Designated as safety issue: No ]
    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.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks ] [ Designated as safety issue: No ]
    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.
  • Progression-Free Survival (PFS) - All Participants [ Time Frame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks ] [ Designated as safety issue: No ]
    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.
  • Duration of Response (DR) [ Time Frame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks ] [ Designated as safety issue: No ]
    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.
  • Overall Survival (OS) [ Time Frame: Baseline up to at least one year after the last patient has been randomized. ] [ Designated as safety issue: Yes ]
    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.
  • Maximum Observed Plasma Concentration (Cmax) of Axitinib [ Time Frame: Cycle 2 Day 15 (C2D15): pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ] [ Designated as safety issue: No ]
    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.
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ] [ Designated as safety issue: No ]
    Tmax for steady-state axitinib was evaluated on Cycle 2 Day 15.
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Axitinib [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ] [ Designated as safety issue: No ]
    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.
  • Area Under the Curve From Time Zero to 24 Hours[AUC(0-24)] for Axitinib [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ] [ Designated as safety issue: No ]
    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.
  • Plasma Decay Half-Life (t1/2) for Axitinib [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ] [ Designated as safety issue: No ]
    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.
  • Apparent Oral Clearance (CL/F) of Axitinib [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ] [ Designated as safety issue: No ]
    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.
  • Apparent Volume of Distribution During the Elimination Phase (Vz/F) for Axitinib [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline in Systolic Blood Pressure [ Time Frame: Baseline up to follow-up visit ] [ Designated as safety issue: Yes ]
    Value at respective visit minus value at baseline
  • Change From Baseline in Diastolic Blood Pressure [ Time Frame: Baseline up to follow-up visit ] [ Designated as safety issue: Yes ]
    Value at respective visit minus value at baseline.
  • Comparison of Circulating Endothelial Cells (CECs) in Blood: Cluster of Differentiation (CD)146+/CD105+ at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.
  • Comparison of the Ratio of CECs in Blood: CD146+/CD105+ at Each Time Point to Baseline [ Time Frame: Cycle 1 Day 1 (C1D1), C1D15, C2D15, End of therapy (EOT) ] [ Designated as safety issue: No ]
    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.
  • Circulating Endothelial Cells (CECs) in Blood: CD31+/CD146+ [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.
  • Comparison of Ratio of CECs in Blood: CD31+/CD146+ at Each Time Point to Baseline [ Time Frame: C1D1, C1D15, C2D15, EOT ] [ Designated as safety issue: No ]
    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.
  • ORR in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms [ Time Frame: Baseline, C1D1 ] [ Designated as safety issue: No ]
    ORR, defined as proportion of participants with CR or PR according to RECIST, in subgroups that were defined by VEGFA or VEGFR3 polymorphisms.
  • PFS in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms [ Time Frame: Baseline, C1D1 ] [ Designated as safety issue: No ]
    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.
  • Progression Free Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Safety Profile [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Response Duration [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Axitinib (AG-013736) With Or Without Dose Titration (Increase) In Patients With Kidney Cancer
Randomized, Double-Blind Phase 2 Study of Axitinib (AG-013736) With Or Without Dose Titration In Patients With Metastatic Renal Cell Carcinoma

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

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Carcinoma, Renal Cell
  • Drug: axitinib
    axitinib 5mg BID (open-label) + axitinib dose titration (blinded)
  • Drug: axitinib
    axitinib 5mg BID (open-label) + placebo dose titration (blinded)
  • Drug: axitinib
    axitinib 5mg BID (open-label)
  • A
    Randomized arm
    Intervention: Drug: axitinib
  • B
    Randomized arm
    Intervention: Drug: axitinib
  • C
    Non-randomized arm
    Intervention: Drug: axitinib
Rini BI, Melichar B, Ueda T, Grünwald 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
213
August 2014
October 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Czech Republic,   Germany,   Japan,   Russian Federation,   Spain
 
NCT00835978
A4061046
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP