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A Study In Patients With Advanced Solid Tumor

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ClinicalTrials.gov Identifier: NCT00726752
Recruitment Status : Completed
First Posted : August 1, 2008
Results First Posted : March 26, 2012
Last Update Posted : May 23, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms
Intervention Drug: Axitinib (AG-013736)
Enrollment 6
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AG-013736
Hide Arm/Group Description Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Period Title: Overall Study
Started 6
Completed 0
Not Completed 6
Reason Not Completed
Lack of Efficacy             6
Arm/Group Title AG-013736
Hide Arm/Group Description Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Baseline Participants 6
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants
53.8  (15.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Female
3
  50.0%
Male
3
  50.0%
1.Primary Outcome
Title Single Dose: Maximum Observed Plasma Concentration (Cmax)
Hide Description [Not Specified]
Time Frame Predose, 0.5, 1, 2, 4, 6, 8, 10, 24, and 32-hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacokinetic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
5 mg Single Dose 20.732  (14.492)
7 mg Single Dose 32.007  (28.223)
10 mg Single Dose 53.123  (60.921)
2.Primary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time Zero to Time Infinity (AUCinf)
Hide Description AUCinf is obtained from AUC (0 - t) plus AUC (t - infinity).
Time Frame Predose, 0.5, 1, 2, 4, 6, 8, 10, 24, and 32-hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacokinetic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
5 mg Single Dose 180.25  (154.90)
7 mg Single Dose 228.45  (183.12)
10 mg Single Dose 379.12  (345.50)
3.Primary Outcome
Title Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Hide Description [Not Specified]
Time Frame Predose, 0.5, 1, 2, 4, 6, 8, 10, 24, and 32-hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacokinetic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: hours
5 mg Single Dose
4.1000
(3.950 to 6.020)
7 mg Single Dose
4.0000
(0.983 to 9.880)
10 mg Single Dose
4.0150
(2.050 to 6.000)
4.Primary Outcome
Title Single Dose: Plasma Decay Half-Life (t1/2)
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame Predose, 0.5, 1, 2, 4, 6, 8, 10, 24, and 32-hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacokinetic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: hours
5 mg Single Dose 4.778  (2.815)
7 mg Single Dose 5.088  (2.592)
10 mg Single Dose 5.880  (3.456)
5.Secondary Outcome
Title Multiple Dose: Maximum Observed Plasma Concentration (Cmax)
Hide Description Cmax at multiple dosing
Time Frame Cycle 1 Day 15 predose in the morning, and 0.5, 1, 2, 4, 8 and 12 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacokinetic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
25.933  (21.703)
6.Secondary Outcome
Title Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Hide Description The dosing interval was 12 hours in this study.
Time Frame Cycle 1 Day 15 predose in the morning, and 0.5, 1, 2, 4, 8 and 12 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacokinetic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
164.55  (128.15)
7.Secondary Outcome
Title Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Hide Description Tmax at multiple dosing
Time Frame Cycle 1 Day 15 predose in the morning, and 0.5, 1, 2, 4, 8 and 12 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacokinetic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: hours
4.0400
(3.930 to 7.700)
8.Secondary Outcome
Title Multiple Dose: Accumulation Ratio for Cmax (Rac Cmax) and Accumulation Ratio for AUCtau (Rac AUCtau)
Hide Description Rac Cmax is obtained from Cmax (Cycle 1, Day 15) divided by Cmax (Cycle 1, Day 1) Rac AUCtau is obtained from AUCtau (Cycle 1, Day 15) divided by AUCtau (Cycle 1, Day 1)
Time Frame Cycle 1 Day 15 predose in the morning, and 0.5, 1, 2, 4, 8 and 12 hour postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacokinetic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ratio
Rac Cmax 1.3540  (0.5335)
Rac AUCtau 1.4185  (0.3951)
9.Secondary Outcome
Title Percent Change From Baseline in Soluble Vascular Endothelial Growth Factor Receptor 1, 2, and 3 (s-VEGFR1, s-VEGFR2 and s-VEGFR3), Vascular Endothelial Growth Factor (VEGF), Soluble Stem Cell Factor Receptor (s-KIT )
Hide Description Percent change from baseline is obtained from (observed value minus baseline value) divided by baseline value multiplied by 100 in each parameter, i.e., s-VEGFR1, VEGFR2, s-VEGFR3, s-KIT, and VEGF
Time Frame Prior to the initial dose (baseline) and Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic analysis set was defined as all enrolled participants who received at least 1 dose of the study medication and who completed pharmacodynamic blood sampling for at least 1 day.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: percent
s-VEGFR1
-29.15
(-31.4 to -25.3)
s-VEGFR2
-33.16
(-58.4 to -26.2)
s-VEGFR3
-56.38
(-66.2 to -42.1)
s-KIT
-14.59
(-23.7 to -5.2)
VEGF
179.52
(37.0 to 1444.6)
10.Secondary Outcome
Title Number of Participants With Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression of Disease (PD) According to the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)
Hide Description CR was defined as the disappearance of all target and nontarget lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (SLD) of the targeted lesions. CR and PR had to be documented on 2 occasions separated by at least 4 weeks. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as PD being demonstrated during the first 8 weeks. PD was defined as at least a 20% increase in the SLD of target lesions compared to the smallest SLD since the study treatment started.
Time Frame Up to 470 days
Hide Outcome Measure Data
Hide Analysis Population Description
Anti-tumor response analysis set was defined as all participants with at least 1 target lesion according to RECIST and who received at least 1 dose of study drug.
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants
CR 0
PR 0
SD 3
PD 3
11.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description Number of participants with any adverse events, adverse events graded as Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade 3 or higher , serious adverse events, and adverse events resulted in discontinuation.
Time Frame Up to 470 days of treatment plus 28-days follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set was defined as all enrolled participants who received the study drug at least once in this study (same as the full analysis set:FAS).
Arm/Group Title AG-013736
Hide Arm/Group Description:
Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants
Any adverse events 6
Any serious adverse events 1
Any Grade-3 or -4 adverse events 4
Any Grade-5 adverse events (= death) 1
Discontinuation due to adverse events 0
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title AG-013736
Hide Arm/Group Description Single Dosing: Participants received single AG-013736 5 mg, followed by 7 mg, and subsequently 10 mg. After the single dose at each dose level, participants were monitored for at least 48 hours prior to the next dosing. Multiple Dosing (28-day cycle ): After the monitoring period following the 10 mg single dose, participants received multiple doses of AG-013736 at 5 mg twice daily (BID) at approximately 12 hours apart. The treatment was continued until participants experienced intolerable toxicity or progressive disease.
All-Cause Mortality
AG-013736
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AG-013736
Affected / at Risk (%)
Total   1/6 (16.67%) 
General disorders   
Disease progression  1 [1]  1/6 (16.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
[1]
Caused death.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
AG-013736
Affected / at Risk (%)
Total   6/6 (100.00%) 
Endocrine disorders   
Thyroiditis chronic  1  1/6 (16.67%) 
Eye disorders   
Eye irritation  1  1/6 (16.67%) 
Gastrointestinal disorders   
Abdominal pain upper  1  1/6 (16.67%) 
Ascites  1  1/6 (16.67%) 
Cheilitis  1  1/6 (16.67%) 
Constipation  1  2/6 (33.33%) 
Diarrhoea  1  3/6 (50.00%) 
Nausea  1  2/6 (33.33%) 
Stomatitis  1  2/6 (33.33%) 
General disorders   
Chest pain  1  1/6 (16.67%) 
Fatigue  1  5/6 (83.33%) 
Mucosal inflammation  1  1/6 (16.67%) 
Oedema  1  2/6 (33.33%) 
Hepatobiliary disorders   
Jaundice cholestatic  1  1/6 (16.67%) 
Infections and infestations   
Nasopharyngitis  1  2/6 (33.33%) 
Paronychia  1  1/6 (16.67%) 
Injury, poisoning and procedural complications   
Contusion  1  1/6 (16.67%) 
Fracture  1  1/6 (16.67%) 
Investigations   
Alanine aminotransferase increased  1  1/6 (16.67%) 
Aspartate aminotransferase increased  1  2/6 (33.33%) 
Blood alkaline phosphatase increased  1  3/6 (50.00%) 
Blood amylase increased  1  3/6 (50.00%) 
Blood cholesterol increased  1  2/6 (33.33%) 
Blood lactate dehydrogenase increased  1  3/6 (50.00%) 
Blood potassium increased  1  1/6 (16.67%) 
Blood thyroid stimulating hormone decreased  1  2/6 (33.33%) 
Blood thyroid stimulating hormone increased  1  4/6 (66.67%) 
Blood urine present  1  1/6 (16.67%) 
Lipase increased  1  1/6 (16.67%) 
Neutrophil count decreased  1  2/6 (33.33%) 
Platelet count decreased  1  1/6 (16.67%) 
Thyroglobulin increased  1  1/6 (16.67%) 
Thyroxine free decreased  1  2/6 (33.33%) 
Thyroxine free increased  1  1/6 (16.67%) 
Tri-iodothyronine free decreased  1  2/6 (33.33%) 
Weight decreased  1  1/6 (16.67%) 
White blood cell count decreased  1  2/6 (33.33%) 
Metabolism and nutrition disorders   
Decreased appetite  1  3/6 (50.00%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/6 (16.67%) 
Myalgia  1  2/6 (33.33%) 
Neck pain  1  1/6 (16.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Cancer pain  1  2/6 (33.33%) 
Nervous system disorders   
Dizziness  1  1/6 (16.67%) 
Headache  1  2/6 (33.33%) 
Neuropathy peripheral  1  3/6 (50.00%) 
Somnolence  1  1/6 (16.67%) 
Renal and urinary disorders   
Proteinuria  1  4/6 (66.67%) 
Reproductive system and breast disorders   
Menstruation irregular  1  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/6 (16.67%) 
Dysphonia  1  2/6 (33.33%) 
Epistaxis  1  2/6 (33.33%) 
Skin and subcutaneous tissue disorders   
Dermatitis  1  1/6 (16.67%) 
Dermatitis acneiform  1  1/6 (16.67%) 
Haemorrhage subcutaneous  1  1/6 (16.67%) 
Palmar-plantar erythrodysaesthesia syndrome  1  4/6 (66.67%) 
Pruritus  1  1/6 (16.67%) 
Rash  1  3/6 (50.00%) 
Telangiectasia  1  1/6 (16.67%) 
Urticaria  1  1/6 (16.67%) 
Vascular disorders   
Hypertension  1  5/6 (83.33%) 
Hypotension  1  2/6 (33.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00726752     History of Changes
Other Study ID Numbers: A4061044
First Submitted: July 30, 2008
First Posted: August 1, 2008
Results First Submitted: February 25, 2012
Results First Posted: March 26, 2012
Last Update Posted: May 23, 2012