Axitinib dose titration (giving a higher dose of the drug above its standard starting dose) among certain patients may improve the response to treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
213
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 v1.0). 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.
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.
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.
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.
Duration of Response (DR)
DR was defined as the time from the first documentation of objective tumor response (complete response - CR or Partial response - PR) 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.
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
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.
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East Bay Medical Oncology/Hematology Medical Associates Inc.
Antioch, California, United States
Comprehensive Blood and Cancer Center
Bakersfield, California, 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
East Bay Medical Oncology/Hematology Medical Associates Inc
San Leandro, California, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 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
...and 55 more locations
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.
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.
Time frame: Cycle 2 Day 15 (C2D15): pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib,
Tmax for steady-state axitinib was evaluated on Cycle 2 Day 15.
Time frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
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.
Time frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
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.
Time frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
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.
Time frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
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.
Time frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
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.
Time frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose
Change From Baseline in Systolic Blood Pressure
Value at respective visit minus value at baseline
Time frame: 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.
Change From Baseline in Diastolic Blood Pressure
Value at respective visit minus value at baseline.
Time frame: 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.
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.
Time frame: At baseline - Beginning of the lead-in period (Cycle 1 Day 1)
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.
Time frame: At end of the lead-in period (Cycle 1 Day 15), Cycle 2 Day 15 and End of therapy (EOT)
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.
Time frame: At baseline - Beginning of the lead-in period (Cycle 1 Day 1)
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.
Time frame: At end of the lead-in period (Cycle 1 Day 15), Cycle 2 Day 15 and End of therapy (EOT)
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.
Time frame: At baseline - Beginning of the lead-in period (Cycle 1 Day 1)
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.
Time frame: At baseline - Beginning of the lead-in period (Cycle 1 Day 1)