Study Of AG-013736 In Patients With Refractory Metastatic Renal Cell Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00282048
• Collaborator: (none)
• Enrollment: 62
• Locations: 5
• Arm: 1
• Duration (Months): 39
• Patients Per Site: 12.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To determine the activity and response rate of AG-013736 in patients with advanced and refractory renal cell cancer, (patients who also failed on sorafenib-based therapy).

Condition or Disease	Intervention/Treatment	Phase
Kidney Neoplasms; Carcinoma, Renal Cell	Drug: AG-013736 (axitinib)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study Of AG-013736 In Patients With Refractory Metastatic Renal Cell Cancer
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AG-013736 (axitinib) AG-013736 single agent in continuous dosing until disease progression or unacceptable toxicity	Drug: AG-013736 (axitinib); AG-013736 5 mg twice daily [bid] continuous dosing in 28 day cycles.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Response (OR) [Baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 152 weeks]

   Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of responses. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum of longest dimensions.

Secondary Outcome Measures

1. Progression-free Survival (PFS) [Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 152 weeks]

   Time in days from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

2. Duration of Response (DR) [Baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 152 weeks]

   Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

3. Overall Survival (OS) [Baseline to death due to any cause or at least 1 year after the first dose for the last participant]

   Time in days from the start of study treatment to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.

4. Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index for Disease Cancer Related Symptoms (FKSI-DRS) Score [Baseline (Day 1 of Cycle 1), Day 1 of all subsequent cycles up to Cycle 38 and follow up (28 days after last dose)]

   FKSI-DRS is a subset of FKSI which is a questionnaire for FACT -Kidney Symptom Index used to assess Quality of Life (QoL)/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions and the FKSI-DRS consisted of 9 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI-DRS ranged between 0-36. Since the questions could be reversed coded, as appropriate, before calculating FKSI-DRS, 0 and 36 could be considered the worst and best health states based on the 9 questions comprising FKSI-DRS.

5. Population Pharmacokinetics of Axitinib (AG-013736) [Day 1 (Pre-dose), Day 29, Day 57 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks]

   Data for this outcome measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

Other Outcome Measures

1. Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index (FKSI) Score [Baseline (Day 1 of Cycle 1), Day 1 of all subsequent cycles up to Cycle 38 and follow up (28 days after last dose)]

   FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.

2. Correlation of Area Under the Concentration-time Curve at Steady State (AUCss) With Confirmed Partial Response (PR) [Day 1 (Pre-dose), Day 29 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks]

   AUCss: pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods, computed as each participant's average total daily dose (accounting for dose reductions and any recorded missed doses) divided by population estimated posthoc individual apparent clearance (CL/F), i.e., AUCss = Daily Dose/(CL/F), where F refers to the oral bioavailability, and CL refers to the systemic clearance. PR: responses with at least 30% decrease in sum of longest dimensions of target lesions using baseline (pre-treatment) sum of longest dimensions as reference. Logistic regression with general linear model was applied to data of PR using AUCss; PR was correlated with AUCss as fold increase in odds of PR with increase in AUCss. Fold increase was calculated as exponent of product of logistic regression slope coefficient and unit change of AUCss.

3. Relationship of Area Under the Concentration-time Curve at Steady State (AUCss) With Progression-free Survival (PFS) [Day 1 (Pre-dose), Day 29, and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks]

   AUCss is a pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods. PFS is median time from first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. Relationship of PFS versus AUCss was determined as median PFS in participants with high AUCss [AUCss greater than or equal to (>=) median AUCss] or low AUCss [AUCss less than (<) median AUCss].

4. Relationship of Area Under the Concentration-time Curve at Steady State (AUCss) With Overall Survival (OS) [Day 1 (Pre-dose), Day 29 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks]

   AUCss is a pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods. OS is time in weeks from the start of study treatment to date of death due to any cause. Relationship of OS versus AUCss was determined as median OS in participants with high AUCss [AUCss >= median AUCss] or low AUCss [AUCss < median AUCss].

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• RCC with metastases and nephrectomy

• failure of prior sorafenib-based therapy

• at least 1 target lesion that has not been irradiated

• adequate bone marrow, hepatic and renal function, > or equal to 18 years of age.

Exclusion Criteria:

• Gastrointestinal abnormalities

• current use or inability to avoid chronic antacid therapy

• current use or anticipated inability to avoid potent CYP3A4 inhibitors or CYP1A2 inducers

• active seizure disorder or evidence of brain metastases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Chicago	Illinois	United States	60637
2	Pfizer Investigational Site	Bronx	New York	United States	10466
3	Pfizer Investigational Site	Cleveland	Ohio	United States	44195
4	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19111-2497
5	Pfizer Investigational Site	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00282048
• Other Study ID Numbers: A4061023
• First Posted: Jan 25, 2006
• Last Update Posted: Jul 31, 2012
• Last Verified: Jul 1, 2012

• Additional relevant MeSH terms: Carcinoma, Renal Cell; Kidney Neoplasms; Axitinib

Study Results

Participant Flow

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Period Title: Overall Study
STARTED	62
COMPLETED	0
NOT COMPLETED	62

Baseline Characteristics

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Overall Participants	62
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.9 (9.4)
Sex: Female, Male (Count of Participants)
Female	20 32.3%
Male	42 67.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of responses. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum of longest dimensions.
Time Frame	Baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 152 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of the study medication, had a baseline assessment of disease and had the correct histological cancer type.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	62
Number (95% Confidence Interval) [Percentage of Participants]	22.6 36.5%

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Time in days from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame	Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 152 weeks

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants who received at least 1 dose of the study medication, had a baseline assessment of disease and had the correct histological cancer type.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	62
Median (95% Confidence Interval) [Days]	225

3. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame	Baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 152 weeks

Outcome Measure Data

Analysis Population Description

Subgroup of participants from the ITT population, with a confirmed objective tumor response (CR or PR).

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	14
Median (95% Confidence Interval) [Days]	531

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Time in days from the start of study treatment to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.
Time Frame	Baseline to death due to any cause or at least 1 year after the first dose for the last participant

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants who received at least 1 dose of the study medication, had a baseline assessment of disease and had the correct histological cancer type.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	62
Median (95% Confidence Interval) [Days]	412.5

5. Secondary Outcome

Title	Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index for Disease Cancer Related Symptoms (FKSI-DRS) Score
Description	FKSI-DRS is a subset of FKSI which is a questionnaire for FACT -Kidney Symptom Index used to assess Quality of Life (QoL)/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions and the FKSI-DRS consisted of 9 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI-DRS ranged between 0-36. Since the questions could be reversed coded, as appropriate, before calculating FKSI-DRS, 0 and 36 could be considered the worst and best health states based on the 9 questions comprising FKSI-DRS.
Time Frame	Baseline (Day 1 of Cycle 1), Day 1 of all subsequent cycles up to Cycle 38 and follow up (28 days after last dose)

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants who received at least 1 dose of the study medication, had a baseline assessment of disease and had the correct histological cancer type. 'n' is the number of participants who completed at least one question.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	62
Baseline (n=62)	28.94
Day 1 (Cycle 2) (n=52)	27.12
Day 1 (Cycle 3) (n=46)	27.11
Day 1 (Cycle 4) (n=41)	27.68
Day 1 (Cycle 5) (n=39)	27.94
Day 1 (Cycle 6) (n=33)	27.31
Day 1 (Cycle 7) (n=32)	28.56
Day 1 (Cycle 8) (n=30)	28.55
Day 1 (Cycle 9) (n=27)	28.75
Day 1 (Cycle 10) (n=19)	29.37
Day 1 (Cycle 11) (n=17)	29.35
Day 1 (Cycle 12) (n=17)	29.24
Day 1 (Cycle 13) (n=16)	30.41
Day 1 (Cycle 14) (n=15)	31.02
Day 1 (Cycle 15) (n=14)	30.29
Day 1 (Cycle 16) (n=14)	30.79
Day 1 (Cycle 17) (n=13)	31.46
Day 1 (Cycle 18) (n=12)	31.08
Day 1 (Cycle 19) (n=9)	29.44
Day 1 (Cycle 20) (n=10)	29.80
Day 1 (Cycle 21) (n=11)	29.91
Day 1 (Cycle 22) (n=10)	30.80
Day 1 (Cycle 23) (n=9)	30.22
Day 1 (Cycle 24) (n=8)	31.75
Day 1 (Cycle 25) (n=7)	31.14
Day 1 (Cycle 26) (n=7)	31.29
Day 1 (Cycle 27) (n=7)	32.00
Day 1 (Cycle 28) (n=5)	34.00
Day 1 (Cycle 29) (n=6)	33.83
Day 1 (Cycle 30) (n=6)	34.00
Day 1 (Cycle 31) (n=4)	33.75
Day 1 (Cycle 32) (n=1)	34.00
Day 1 (Cycle 33) (n=1)	34.00
Day 1 (Cycle 34) (n=0)	NA
Day 1 (Cycle 35) (n=1)	33.00
Day 1 (Cycle 36) (n=1)	33.00
Day 1 (Cycle 37) (n=1)	29.00
Day 1 (Cycle 38) (n=1)	30.00
at Follow Up (n=9)	25.11

6. Secondary Outcome

Title	Population Pharmacokinetics of Axitinib (AG-013736)
Description	Data for this outcome measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time Frame	Day 1 (Pre-dose), Day 29, Day 57 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index (FKSI) Score
Description	FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.
Time Frame	Baseline (Day 1 of Cycle 1), Day 1 of all subsequent cycles up to Cycle 38 and follow up (28 days after last dose)

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants who received at least 1 dose of the study medication, had a baseline assessment of disease and had the correct histological cancer type. 'n' is the number of participants who completed at least one question.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	62
Baseline (n=62)	44.84
Day 1 (Cycle 2) (n=52)	41.40
Day 1 (Cycle 3) (n=46)	41.62
Day 1 (Cycle 4) (n=41)	42.26
Day 1 (Cycle 5) (n=39)	42.35
Day 1 (Cycle 6) (n=33)	41.65
Day 1 (Cycle 7) (n=32)	43.77
Day 1 (Cycle 8) (n=30)	44.00
Day 1 (Cycle 9) (n=27)	44.80
Day 1 (Cycle 10) (n=19)	45.39
Day 1 (Cycle 11) (n=17)	44.14
Day 1 (Cycle 12) (n=17)	44.73
Day 1 (Cycle 13) (n=16)	46.13
Day 1 (Cycle 14) (n=15)	47.04
Day 1 (Cycle 15) (n=14)	45.93
Day 1 (Cycle 16) (n=14)	46.16
Day 1 (Cycle 17) (n=13)	48.14
Day 1 (Cycle 18) (n=12)	47.08
Day 1 (Cycle 19) (n=9)	44.98
Day 1 (Cycle 20) (n=10)	45.81
Day 1 (Cycle 21) (n=11)	47.02
Day 1 (Cycle 22) (n=10)	47.50
Day 1 (Cycle 23) (n=9)	46.30
Day 1 (Cycle 24) (n=8)	48.64
Day 1 (Cycle 25) (n=7)	49.11
Day 1 (Cycle 26) (n=7)	50.26
Day 1 (Cycle 27) (n=7)	49.82
Day 1 (Cycle 28) (n=5)	53.20
Day 1 (Cycle 29) (n=6)	52.67
Day 1 (Cycle 30) (n=6)	53.17
Day 1 (Cycle 31) (n=4)	53.00
Day 1 (Cycle 32) (n=1)	53.00
Day 1 (Cycle 33) (n=1)	51.00
Day 1 (Cycle 34) (n=0)	NA
Day 1 (Cycle 35) (n=1)	51.00
Day 1 (Cycle 36) (n=1)	51.00
Day 1 (Cycle 37) (n=1)	45.00
Day 1 (Cycle 38) (n=1)	48.00
At Follow Up (n=9)	38.98

8. Other Pre-specified Outcome

Title	Correlation of Area Under the Concentration-time Curve at Steady State (AUCss) With Confirmed Partial Response (PR)
Description	AUCss: pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods, computed as each participant's average total daily dose (accounting for dose reductions and any recorded missed doses) divided by population estimated posthoc individual apparent clearance (CL/F), i.e., AUCss = Daily Dose/(CL/F), where F refers to the oral bioavailability, and CL refers to the systemic clearance. PR: responses with at least 30% decrease in sum of longest dimensions of target lesions using baseline (pre-treatment) sum of longest dimensions as reference. Logistic regression with general linear model was applied to data of PR using AUCss; PR was correlated with AUCss as fold increase in odds of PR with increase in AUCss. Fold increase was calculated as exponent of product of logistic regression slope coefficient and unit change of AUCss.
Time Frame	Day 1 (Pre-dose), Day 29 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks

Outcome Measure Data

Analysis Population Description

Participants for whom both Pharmacokinetic (PK) and PR data were available were included in analysis.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	14
Fold change per 1 ng*hr/mL: Cycle1	1.0028
Fold change per 100 ng*hr/mL: Cycle1	1.3300

9. Other Pre-specified Outcome

Title	Relationship of Area Under the Concentration-time Curve at Steady State (AUCss) With Progression-free Survival (PFS)
Description	AUCss is a pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods. PFS is median time from first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. Relationship of PFS versus AUCss was determined as median PFS in participants with high AUCss [AUCss greater than or equal to (>=) median AUCss] or low AUCss [AUCss less than (<) median AUCss].
Time Frame	Day 1 (Pre-dose), Day 29, and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks

Outcome Measure Data

Analysis Population Description

Participants for whom both PK and PFS data were available were included in analysis. 'n' signifies number of participants evaluable for the corresponding category.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	57
PFS at Low AUCss: Cycle1 (n=28)	31
PFS at High AUCss: Cycle1 (n=29)	39

10. Other Pre-specified Outcome

Title	Relationship of Area Under the Concentration-time Curve at Steady State (AUCss) With Overall Survival (OS)
Description	AUCss is a pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods. OS is time in weeks from the start of study treatment to date of death due to any cause. Relationship of OS versus AUCss was determined as median OS in participants with high AUCss [AUCss >= median AUCss] or low AUCss [AUCss < median AUCss].
Time Frame	Day 1 (Pre-dose), Day 29 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks

Outcome Measure Data

Analysis Population Description

Participants for whom both PK and OS data were available were included in analysis. 'n' signifies number of participants evaluable for the corresponding category.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
Measure Participants	57
OS at Low AUCss: Cycle1 (n=28)	43
OS at High AUCss: Cycle1 (n=29)	88

Adverse Events

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	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) for 4 consecutive weeks (28 days cycle) with no interval between cycles.
All Cause Mortality
	Axitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Axitinib
	Affected / at Risk (%)	# Events
Total	39/62 (62.9%)
Cardiac disorders
Atrial fibrillation	1/62 (1.6%)
Atrial tachycardia	1/62 (1.6%)
Bradycardia	1/62 (1.6%)
Bundle branch block left	1/62 (1.6%)
Cardiac disorder	1/62 (1.6%)
Cardiac failure congestive	2/62 (3.2%)
Left ventricular dysfunction	1/62 (1.6%)
Myocardial ischaemia	2/62 (3.2%)
Tachycardia	1/62 (1.6%)
Gastrointestinal disorders
Abdominal distension	2/62 (3.2%)
Abdominal pain	5/62 (8.1%)
Abdominal pain upper	1/62 (1.6%)
Diverticulum	1/62 (1.6%)
Gastrointestinal perforation	1/62 (1.6%)
Haematochezia	1/62 (1.6%)
Large intestine perforation	1/62 (1.6%)
Nausea	4/62 (6.5%)
Vomiting	4/62 (6.5%)
General disorders
Chest pain	1/62 (1.6%)
Death	1/62 (1.6%)
Disease progression	4/62 (6.5%)
Fatigue	2/62 (3.2%)
Oedema peripheral	1/62 (1.6%)
Hepatobiliary disorders
Hepatorenal syndrome	1/62 (1.6%)
Hyperbilirubinaemia	1/62 (1.6%)
Jaundice	1/62 (1.6%)
Infections and infestations
Cholecystitis infective	1/62 (1.6%)
Peritoneal infection	1/62 (1.6%)
Pneumonia	2/62 (3.2%)
Wound infection	1/62 (1.6%)
Injury, poisoning and procedural complications
Wound complication	1/62 (1.6%)
Investigations
Blood alkaline phosphatase increased	1/62 (1.6%)
Blood creatinine increased	1/62 (1.6%)
Lipase increased	1/62 (1.6%)
Metabolism and nutrition disorders
Dehydration	6/62 (9.7%)
Hypercalcaemia	2/62 (3.2%)
Musculoskeletal and connective tissue disorders
Back pain	2/62 (3.2%)
Nervous system disorders
Ataxia	1/62 (1.6%)
Cerebral haemorrhage	2/62 (3.2%)
Convulsion	1/62 (1.6%)
Dizziness	1/62 (1.6%)
Headache	1/62 (1.6%)
Lethargy	2/62 (3.2%)
Syncope	2/62 (3.2%)
Psychiatric disorders
Agitation	1/62 (1.6%)
Confusional state	2/62 (3.2%)
Mental status changes	1/62 (1.6%)
Renal and urinary disorders
Anuria	1/62 (1.6%)
Renal failure	1/62 (1.6%)
Respiratory, thoracic and mediastinal disorders
Cough	1/62 (1.6%)
Dyspnoea	7/62 (11.3%)
Pleural effusion	2/62 (3.2%)
Pleuritic pain	1/62 (1.6%)
Pneumothorax	1/62 (1.6%)
Pulmonary embolism	1/62 (1.6%)
Respiratory distress	1/62 (1.6%)
Vascular disorders
Deep vein thrombosis	1/62 (1.6%)
Embolism arterial	1/62 (1.6%)
Hypertension	3/62 (4.8%)
Hypotension	5/62 (8.1%)
Thrombosis	1/62 (1.6%)
Other (Not Including Serious) Adverse Events
	Axitinib
	Affected / at Risk (%)	# Events
Total	62/62 (100%)
Blood and lymphatic system disorders
Anaemia	3/62 (4.8%)
Polycythaemia	1/62 (1.6%)
Thrombocytopenia	3/62 (4.8%)
Cardiac disorders
Left ventricular hypertrophy	1/62 (1.6%)
Palpitations	1/62 (1.6%)
Sinus tachycardia	1/62 (1.6%)
Tachycardia	2/62 (3.2%)
Ventricular hypokinesia	1/62 (1.6%)
Ear and labyrinth disorders
Hypoacusis	1/62 (1.6%)
Tinnitus	1/62 (1.6%)
Endocrine disorders
Hypothyroidism	11/62 (17.7%)
Eye disorders
Blindness	1/62 (1.6%)
Conjunctival haemorrhage	1/62 (1.6%)
Dry eye	1/62 (1.6%)
Eye pruritus	1/62 (1.6%)
Lacrimation increased	1/62 (1.6%)
Ocular hyperaemia	1/62 (1.6%)
Scleral haemorrhage	1/62 (1.6%)
Vitreous floaters	1/62 (1.6%)
Gastrointestinal disorders
Abdominal discomfort	1/62 (1.6%)
Abdominal distension	4/62 (6.5%)
Abdominal pain	11/62 (17.7%)
Abdominal pain lower	1/62 (1.6%)
Abdominal pain upper	3/62 (4.8%)
Anorectal discomfort	1/62 (1.6%)
Cheilitis	1/62 (1.6%)
Constipation	16/62 (25.8%)
Diarrhoea	38/62 (61.3%)
Dry mouth	5/62 (8.1%)
Dyspepsia	12/62 (19.4%)
Dysphagia	2/62 (3.2%)
Erosive oesophagitis	1/62 (1.6%)
Eructation	4/62 (6.5%)
Flatulence	5/62 (8.1%)
Gastritis	1/62 (1.6%)
Gastrointestinal haemorrhage	1/62 (1.6%)
Gastrooesophageal reflux disease	3/62 (4.8%)
Gingivitis	1/62 (1.6%)
Glossodynia	3/62 (4.8%)
Haematochezia	1/62 (1.6%)
Haemorrhoids	2/62 (3.2%)
Impaired gastric emptying	1/62 (1.6%)
Large intestinal ulcer	1/62 (1.6%)
Nausea	27/62 (43.5%)
Oral pain	7/62 (11.3%)
Proctalgia	3/62 (4.8%)
Rectal fissure	1/62 (1.6%)
Rectal haemorrhage	3/62 (4.8%)
Stomatitis	11/62 (17.7%)
Tongue ulceration	1/62 (1.6%)
Vomiting	19/62 (30.6%)
General disorders
Asthenia	1/62 (1.6%)
Axillary pain	1/62 (1.6%)
Chest pain	6/62 (9.7%)
Chills	7/62 (11.3%)
Fatigue	47/62 (75.8%)
Hypothermia	1/62 (1.6%)
Impaired healing	1/62 (1.6%)
Influenza like illness	1/62 (1.6%)
Mucosal inflammation	21/62 (33.9%)
Non-cardiac chest pain	1/62 (1.6%)
Oedema peripheral	11/62 (17.7%)
Pain	7/62 (11.3%)
Pyrexia	9/62 (14.5%)
Suprapubic pain	1/62 (1.6%)
Temperature intolerance	2/62 (3.2%)
Hepatobiliary disorders
Bile duct obstruction	1/62 (1.6%)
Immune system disorders
Hypersensitivity	3/62 (4.8%)
Seasonal allergy	1/62 (1.6%)
Infections and infestations
Abscess	1/62 (1.6%)
Bacteraemia	1/62 (1.6%)
Bronchitis	2/62 (3.2%)
Candidiasis	1/62 (1.6%)
Ear infection	1/62 (1.6%)
Folliculitis	1/62 (1.6%)
Herpes zoster	1/62 (1.6%)
Localised infection	1/62 (1.6%)
Oral candidiasis	1/62 (1.6%)
Oral fungal infection	1/62 (1.6%)
Oral infection	2/62 (3.2%)
Pharyngitis	5/62 (8.1%)
Pneumonia	4/62 (6.5%)
Rhinitis	4/62 (6.5%)
Septic shock	1/62 (1.6%)
Sinusitis	5/62 (8.1%)
Tinea pedis	1/62 (1.6%)
Tooth abscess	1/62 (1.6%)
Upper respiratory tract infection	4/62 (6.5%)
Urinary tract infection	8/62 (12.9%)
Vaginal infection	1/62 (1.6%)
Vulvovaginal mycotic infection	3/62 (4.8%)
Wound infection	1/62 (1.6%)
Injury, poisoning and procedural complications
Contusion	2/62 (3.2%)
Gastrointestinal injury	1/62 (1.6%)
Procedural pain	1/62 (1.6%)
Splinter	1/62 (1.6%)
Investigations
Activated partial thromboplastin time prolonged	1/62 (1.6%)
Alanine aminotransferase	1/62 (1.6%)
Alanine aminotransferase increased	2/62 (3.2%)
Aspartate aminotransferase	2/62 (3.2%)
Aspartate aminotransferase increased	3/62 (4.8%)
Blood alkaline phosphatase increased	1/62 (1.6%)
Blood amylase increased	1/62 (1.6%)
Blood bilirubin increased	1/62 (1.6%)
Blood cholesterol increased	1/62 (1.6%)
Blood creatine increased	2/62 (3.2%)
Blood creatinine increased	4/62 (6.5%)
Blood lactate dehydrogenase increased	1/62 (1.6%)
Blood triglycerides increased	1/62 (1.6%)
Breath sounds abnormal	1/62 (1.6%)
International normalised ratio	1/62 (1.6%)
International normalised ratio increased	2/62 (3.2%)
Lipase increased	1/62 (1.6%)
Urobilinogen urine increased	1/62 (1.6%)
Weight decreased	19/62 (30.6%)
Metabolism and nutrition disorders
Decreased appetite	33/62 (53.2%)
Dehydration	8/62 (12.9%)
Hypercalcaemia	1/62 (1.6%)
Hyperkalaemia	1/62 (1.6%)
Hyperlipasaemia	1/62 (1.6%)
Hypocalcaemia	1/62 (1.6%)
Hypokalaemia	1/62 (1.6%)
Hyponatraemia	1/62 (1.6%)
Vitamin B12 deficiency	1/62 (1.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	16/62 (25.8%)
Arthritis	2/62 (3.2%)
Back pain	8/62 (12.9%)
Bone pain	6/62 (9.7%)
Flank pain	2/62 (3.2%)
Groin pain	2/62 (3.2%)
Joint swelling	1/62 (1.6%)
Muscle spasms	4/62 (6.5%)
Muscle tightness	1/62 (1.6%)
Muscular weakness	3/62 (4.8%)
Musculoskeletal chest pain	4/62 (6.5%)
Musculoskeletal discomfort	1/62 (1.6%)
Musculoskeletal pain	3/62 (4.8%)
Myalgia	11/62 (17.7%)
Neck pain	2/62 (3.2%)
Pain in extremity	13/62 (21%)
Pain in jaw	1/62 (1.6%)
Pubic pain	1/62 (1.6%)
Nervous system disorders
Ageusia	1/62 (1.6%)
Aphonia	1/62 (1.6%)
Balance disorder	1/62 (1.6%)
Brain mass	1/62 (1.6%)
Cognitive disorder	1/62 (1.6%)
Convulsion	1/62 (1.6%)
Dizziness	11/62 (17.7%)
Dysgeusia	14/62 (22.6%)
Extrapyramidal disorder	1/62 (1.6%)
Headache	16/62 (25.8%)
Hyperaesthesia	2/62 (3.2%)
Hypoaesthesia	1/62 (1.6%)
Neuropathy peripheral	1/62 (1.6%)
Paraesthesia	6/62 (9.7%)
Peripheral sensory neuropathy	2/62 (3.2%)
Peroneal nerve palsy	2/62 (3.2%)
Sciatica	3/62 (4.8%)
Tremor	2/62 (3.2%)
Psychiatric disorders
Anxiety	6/62 (9.7%)
Confusional state	3/62 (4.8%)
Depression	10/62 (16.1%)
Disorientation	1/62 (1.6%)
Insomnia	6/62 (9.7%)
Renal and urinary disorders
Bladder spasm	1/62 (1.6%)
Dysuria	3/62 (4.8%)
Glycosuria	1/62 (1.6%)
Haematuria	1/62 (1.6%)
Micturition urgency	2/62 (3.2%)
Nocturia	1/62 (1.6%)
Pollakiuria	3/62 (4.8%)
Proteinuria	8/62 (12.9%)
Renal failure	1/62 (1.6%)
Urinary hesitation	1/62 (1.6%)
Urinary retention	1/62 (1.6%)
Reproductive system and breast disorders
Breast oedema	1/62 (1.6%)
Erectile dysfunction	1/62 (1.6%)
Genital rash	1/62 (1.6%)
Scrotal disorder	1/62 (1.6%)
Respiratory, thoracic and mediastinal disorders
Cough	17/62 (27.4%)
Dysphonia	23/62 (37.1%)
Dyspnoea	21/62 (33.9%)
Dyspnoea exertional	2/62 (3.2%)
Epistaxis	10/62 (16.1%)
Hiccups	3/62 (4.8%)
Hypoxia	1/62 (1.6%)
Nasal congestion	3/62 (4.8%)
Oropharyngeal pain	5/62 (8.1%)
Pleural effusion	1/62 (1.6%)
Pleuritic pain	1/62 (1.6%)
Productive cough	3/62 (4.8%)
Pulmonary haemorrhage	1/62 (1.6%)
Rhinorrhoea	4/62 (6.5%)
Sinus congestion	1/62 (1.6%)
Upper-airway cough syndrome	1/62 (1.6%)
Wheezing	1/62 (1.6%)
Skin and subcutaneous tissue disorders
Alopecia	5/62 (8.1%)
Dry skin	9/62 (14.5%)
Erythema	4/62 (6.5%)
Hair texture abnormal	2/62 (3.2%)
Hidradenitis	1/62 (1.6%)
Hyperhidrosis	2/62 (3.2%)
Hyperkeratosis	4/62 (6.5%)
Nail discolouration	1/62 (1.6%)
Night sweats	4/62 (6.5%)
Pain of skin	2/62 (3.2%)
Palmar erythema	1/62 (1.6%)
Palmar-plantar erythrodysaesthesia syndrome	21/62 (33.9%)
Petechiae	1/62 (1.6%)
Plantar erythema	1/62 (1.6%)
Pruritus	4/62 (6.5%)
Psoriasis	1/62 (1.6%)
Rash	1/62 (1.6%)
Rosacea	1/62 (1.6%)
Skin disorder	1/62 (1.6%)
Skin exfoliation	2/62 (3.2%)
Skin reaction	1/62 (1.6%)
Skin ulcer	2/62 (3.2%)
Swelling face	1/62 (1.6%)
Surgical and medical procedures
Wound drainage	1/62 (1.6%)
Vascular disorders
Flushing	5/62 (8.1%)
Haemorrhage	1/62 (1.6%)
Hot flush	1/62 (1.6%)
Hypertension	26/62 (41.9%)
Hypotension	7/62 (11.3%)
Thrombosis	1/62 (1.6%)

Limitations/Caveats

Population pharmacokinetics was not presented, as the data was not available for the single study and data of other axitinib (AG-013736) Phase 2 studies would be pooled together in a separate report.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.