Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study Of AG-013736 (Axitinib) In Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00447005
Recruitment Status : Completed
First Posted : March 13, 2007
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 Carcinoma
Intervention Drug: Axitinib (AG-013736)
Enrollment 12
Recruitment Details  
Pre-assignment Details Six participants initially received a single dose of AG-013736 5 mg followed by 5 mg twice daily (BID) multiple dosing. They were monitored for dose limiting toxicity (DLT) up to multiple dosing Cycle 1. Since no more than 1 of the first 6 participants had a DLT, 6 additional participants initiated AG-013736 from multiple dosing per the protocol.
Arm/Group Title AG-013736
Hide Arm/Group Description

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Period Title: Overall Study
Started 12
Completed 0
Not Completed 12
Reason Not Completed
Adverse Event             1
Lack of Efficacy             11
Arm/Group Title AG-013736
Hide Arm/Group Description

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Baseline Participants 12
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants
60.2  (13.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
5
  41.7%
Male
7
  58.3%
1.Primary 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 Version 3.0 (CTCAE) Grade 3 or higher, serious adverse events, and adverse events resulted in discontinuation.
Time Frame Up to 795 days of treatment plus 28-days follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of the study drug.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: participants
Any adverse events 12
Any serious adverse events 5
Any Grade-3 or -4 adverse events 7
Any Grade-5 adverse events (= death) 0
Discontinuation due to adverse events 1
2.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax): Single Dose
Hide Description [Not Specified]
Time Frame Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacokinetic blood sampling for at least one day (Pharmacokinetic Analysis Set). Only the first 6 participants were administered a single dose.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
29.97  (9.97)
3.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax): Single Dose
Hide Description [Not Specified]
Time Frame Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacokinetic blood sampling for at least one day (Pharmacokinetic Analysis Set). Only the first 6 participants were administered a single dose.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: hours
4
(2 to 6)
4.Secondary Outcome
Title Area Under The Plasma Concentration-Time Curve From Time Zero to Time Infinity (AUCinf): Single Dose
Hide Description AUCinf is obtained from AUC (0 - t) plus AUC (t - infinity).
Time Frame Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacokinetic blood sampling for at least one day (Pharmacokinetic Analysis Set). Only the first 6 participants were administered a single dose.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
210.3  (146.5)
5.Secondary Outcome
Title Terminal Phase Plasma Half-Life (t1/2): Single Dose
Hide Description t1/2 is the time measured for the plasma concentration to decrease by one half.
Time Frame Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacokinetic blood sampling for at least one day (Pharmacokinetic Analysis Set). Only the first 6 participants were administered a single dose.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: hours
4.8  (1.146)
6.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax): Multiple Dose
Hide Description [Not Specified]
Time Frame Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacokinetic blood sampling for at least one day (Pharmacokinetic Analysis Set); n= number of participants assessed.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1 Day 1 (n=12) 23.85  (10.94)
Cycle 1 Day 15 (n=11) 32.14  (18.04)
7.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax): Multiple Dose
Hide Description [Not Specified]
Time Frame Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacokinetic blood sampling for at least one day (Pharmacokinetic Analysis Set); n= number of participants assessed.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: hours
Cycle 1 Day 1 (n=12)
3
(2 to 4)
Cycle 1 Day 15 (n=11)
4
(1 to 4)
8.Secondary Outcome
Title Area Under The Plasma Concentration-Time Curve Over Dosing Interval Tau (AUCtau): Multiple Dose
Hide Description Dosing Interval was 12 hours in this study.
Time Frame Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacokinetic blood sampling for at least one day (Pharmacokinetic Analysis Set); n= number of participants assessed.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
Cycle 1 Day 1 (n=12) 137.3  (84.3)
Cycle 1 Day 15 (n=11) 187.8  (125.3)
9.Secondary Outcome
Title Accumulation Ratio for Cmax (Rac Cmax) and Accumulation Ratio for AUCtau (Rac AUCtau): Multiple Dose
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 Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacokinetic blood sampling for at least one day (Pharmacokinetic Analysis Set); n= number of participants assessed.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ratio
Rac Cmax (n=11) 1.449  (0.471)
Rac AUCtau (n=11) 1.541  (0.489)
10.Secondary Outcome
Title Percent Change From Baseline in Soluble Vascular Endothelial Growth Factor Receptor 2 and 3 (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., VEGFR2, s-VEGFR3, s-KIT, and VEGF.
Time Frame Prior to the initial dose (baseline), Day 1 of Cycle 2 and at the discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one study drug and completed pharmacodynamic blood sampling for at least one day (Pharmacodynamic Analysis Set); n= number of participants assessed.
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: percent change
s-VEGFR2: Cycle 2 Day 1 (n=12)
-41.73
(-53.2 to -10.1)
s-VEGFR2: At discontinuation (n=11)
-40.57
(-53.0 to -8.4)
s-VEGFR3: Cycle 2 Day 1 (n=12)
-52.50
(-93.7 to -15.6)
s-VEGFR3: At discontinuation (n=11)
-65.48
(-81.2 to 39.4)
s-KIT: Cycle 2 Day 1 (n=12)
-0.26
(-23.8 to 33.5)
s-KIT: At discontinuation (n=11)
4.66
(-31.2 to 12.9)
VEGF: Cycle 2 Day 1 (n=12)
266.92
(14.9 to 1030.4)
VEGF: At discontinuation (n=11)
43.48
(-15.5 to 423.1)
11.Secondary Outcome
Title The Numbers 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 795 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with at least 1 target lesion according to RECIST and who received at least 1 dose of study drug (Anti-tumor Response Analysis Set).
Arm/Group Title AG-013736
Hide Arm/Group Description:

Single dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: participants
CR 0
PR 0
SD 10
PD 2
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 dose (first 6 participants only): Single AG-013736 5 mg was administered orally.

Multiple dose (all participants): AG-013736 5 mg twice daily (BID) was administered orally in fed state, 12 hours apart at approximately the same time each day. AG-013736 dose was titrated or reduced based on the dose modification criteria: the available dose was 2, 3, 5, 7, or 10 mg at a time. One cycle length was 28 days and participants continued the study treatment until intolerable toxicity or disease progression occurred.

All-Cause Mortality
AG-013736
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AG-013736
Affected / at Risk (%)
Total   5/12 (41.67%) 
Cardiac disorders   
Cardiac tamponade  1  1/12 (8.33%) 
Gastrointestinal disorders   
Intestinal obstruction  1  2/12 (16.67%) 
General disorders   
Pyrexia  1  2/12 (16.67%) 
Infections and infestations   
Liver abscess  1  1/12 (8.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
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   12/12 (100.00%) 
Blood and lymphatic system disorders   
Lymphopenia  1  1/12 (8.33%) 
Neutropenia  1  1/12 (8.33%) 
Cardiac disorders   
Palpitations  1  1/12 (8.33%) 
Ear and labyrinth disorders   
Ear discomfort  1  1/12 (8.33%) 
Endocrine disorders   
Hyperthyroidism  1  1/12 (8.33%) 
Gastrointestinal disorders   
Abdominal discomfort  1  1/12 (8.33%) 
Abdominal pain  1  5/12 (41.67%) 
Constipation  1  6/12 (50.00%) 
Diarrhoea  1  10/12 (83.33%) 
Dyspepsia  1  2/12 (16.67%) 
Nausea  1  4/12 (33.33%) 
Proctalgia  1  1/12 (8.33%) 
Stomatitis  1  9/12 (75.00%) 
Toothache  1  2/12 (16.67%) 
General disorders   
Face oedema  1  1/12 (8.33%) 
Fatigue  1  10/12 (83.33%) 
Generalised oedema  1  1/12 (8.33%) 
Pyrexia  1  1/12 (8.33%) 
Thirst  1  1/12 (8.33%) 
Infections and infestations   
Herpes zoster  1  1/12 (8.33%) 
Nasopharyngitis  1  3/12 (25.00%) 
Onychomycosis  1  1/12 (8.33%) 
Tinea infection  1  1/12 (8.33%) 
Investigations   
Alanine aminotransferase increased  1  3/12 (25.00%) 
Aspartate aminotransferase increased  1  6/12 (50.00%) 
Blood albumin decreased  1  1/12 (8.33%) 
Blood alkaline phosphatase increased  1  6/12 (50.00%) 
Blood amylase increased  1  1/12 (8.33%) 
Blood bilirubin increased  1  3/12 (25.00%) 
Blood creatinine increased  1  1/12 (8.33%) 
Blood glucose increased  1  5/12 (41.67%) 
Blood thyroid stimulating hormone decreased  1  4/12 (33.33%) 
Blood thyroid stimulating hormone increased  1  9/12 (75.00%) 
Blood urea increased  1  1/12 (8.33%) 
Blood urine present  1  7/12 (58.33%) 
Haemoglobin decreased  1  1/12 (8.33%) 
Lipase increased  1  5/12 (41.67%) 
Platelet count decreased  1  5/12 (41.67%) 
Thyroxine free decreased  1  1/12 (8.33%) 
Thyroxine free increased  1  3/12 (25.00%) 
Tri-iodothyronine free increased  1  3/12 (25.00%) 
Urine bilirubin increased  1  2/12 (16.67%) 
Weight decreased  1  4/12 (33.33%) 
White blood cell count decreased  1  3/12 (25.00%) 
Metabolism and nutrition disorders   
Decreased appetite  1  11/12 (91.67%) 
Hypoalbuminaemia  1  1/12 (8.33%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/12 (8.33%) 
Back pain  1  3/12 (25.00%) 
Musculoskeletal pain  1  2/12 (16.67%) 
Musculoskeletal stiffness  1  1/12 (8.33%) 
Myalgia  1  1/12 (8.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumour associated fever  1  1/12 (8.33%) 
Tumour pain  1  2/12 (16.67%) 
Nervous system disorders   
Dysgeusia  1  1/12 (8.33%) 
Headache  1  3/12 (25.00%) 
Lacunar infarction  1  1/12 (8.33%) 
Post herpetic neuralgia  1  1/12 (8.33%) 
Somnolence  1  2/12 (16.67%) 
Psychiatric disorders   
Insomnia  1  2/12 (16.67%) 
Renal and urinary disorders   
Proteinuria  1  6/12 (50.00%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  4/12 (33.33%) 
Dysphonia  1  7/12 (58.33%) 
Dyspnoea  1  2/12 (16.67%) 
Dyspnoea exertional  1  1/12 (8.33%) 
Epistaxis  1  3/12 (25.00%) 
Haemoptysis  1  1/12 (8.33%) 
Nasal mucosal disorder  1  1/12 (8.33%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  1/12 (8.33%) 
Erythema  1  1/12 (8.33%) 
Palmar-plantar erythrodysaesthesia syndrome  1  8/12 (66.67%) 
Rash  1  3/12 (25.00%) 
Vascular disorders   
Hypertension  1  6/12 (50.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
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: NCT00447005     History of Changes
Other Study ID Numbers: A4061022
First Submitted: March 12, 2007
First Posted: March 13, 2007
Results First Submitted: February 25, 2012
Results First Posted: March 26, 2012
Last Update Posted: May 23, 2012