Study Of AG-013736 In Patients With 131I-Refractory Thyroid Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00389441
• Collaborator: (none)
• Enrollment: 52
• Locations: 26
• Arm: 1
• Duration (Months): 69
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary purpose is to determine how effective AG-013736 is in shrinking thyroid cancer that is resistant to radioactive iodine

Condition or Disease	Intervention/Treatment	Phase
Thyroid Neoplasms	Drug: AG-013736	Phase 2

Detailed Description

Additional study details: assess safety and efficacy

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: A Pivotal Phase 2 Study Of The Anti-Angiogenesis Agent AG-013736 In Patients With 131I-Refractory Metastatic Or Unresectable Locally-Advanced Thyroid Cancer
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: AG-013736; AG-013736, tablets 5 mg BID , treatment will continue until tumor progression or toxicity

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Response (OR) [Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up)]

   Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST). CR: disappearance of all target/non-target lesions and no appearance of new lesions. PR: at least (>=)30 percent(%) decrease in sum of the longest dimensions (LDs) of the target lesions (taking as a reference the baseline sum), without progression of non-target lesions and no appearance of new lesions. Confirmed responses: those persist on repeat imaging study >=4 weeks after initial documentation of response.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up)]

   PFS: Time in weeks from the start of study treatment to first documentation of objective disease progression or to death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of first dose of study treatment plus 1) divided by 7. Progression is defined using RECIST, as >=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD since start of study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

2. Duration of Response (DR) [Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up)]

   Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. 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 2 year after the first dose for the last participant]

   Time in weeks 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) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

4. Change From Baseline in MD Anderson Symptom Assessment Inventory (MDASI) Symptom Severity Score [Baseline, Cycle 1 Day 15 (C1D15), C2D1, C2D15, thereafter D1 of each cycle up to 28 days after last dose (follow-up)]

   Symptom severity score is comprised of average of 13 MDASI core items (pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting, numbness or tingling). Participants were asked to rate severity of each symptom at their worst in last 24 hours; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Total average score range: 0 to 10. Lower scores indicated better outcome.

5. Change From Baseline in MD Anderson Symptom Assessment Inventory (MDASI) Symptom Interference Score [Baseline, Cycle 1 Day 15 (C1D15), C2D1, C2D15, thereafter D1 of each cycle up to 28 days after last dose (follow-up)]

   Symptom interference score is comprised of average of 6 function items from MDASI core (general activity, mood, work, relations with others, walking, and enjoyment of life). Participants were asked to rate how much symptoms have interfered in last 24 hours; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Total average score range: 0 to 10. Lower scores indicated better outcome.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Radioiodine-refractory metastatic or unresectable locally-advanced thyroid cancer

• At least 1 measurable target lesion, as defined by RECIST

Exclusion Criteria:

• Thyroid lymphoma

• Previous treatment with anti-angiogenesis agents

• No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism within 12 months prior.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Orange	California	United States	92868
2	Pfizer Investigational Site	Aurora	Colorado	United States	80010
3	Pfizer Investigational Site	Tampa	Florida	United States	33612
4	Pfizer Investigational Site	Chicago	Illinois	United States	60637-1470
5	Pfizer Investigational Site	Wichita	Kansas	United States	67226
6	Pfizer Investigational Site	Witchita	Kansas	United States	67220
7	Pfizer Investigational Site	Boston	Massachusetts	United States	02114
8	Pfizer Investigational Site	Boston	Massachusetts	United States	02115
9	Pfizer Investigational Site	Boston	Massachusetts	United States	02215
10	Pfizer Investigational Site	Buffalo	New York	United States	14263
11	Pfizer Investigational Site	Edmonton	Alberta	Canada	T6G 1Z2
12	Pfizer Investigational Site	London	Ontario	Canada	N6A 4L6
13	Pfizer Investigational Site	Montreal	Quebec	Canada	H2L 4M1
14	Pfizer Investigational Site	Nanjing	Jiangsu	China	210002
15	Pfizer Investigational Site	Beijing		China	100021
16	Pfizer Investigational Site	Shanghai		China	20001/200127
17	Pfizer Investigational Site	Shanghai		China	200233
18	Pfizer Investigational Site	Praha 5		Czech Republic	150 06
19	Pfizer Investigational Site	Vellore	Tamil Nadu	India	632 004
20	Pfizer Investigational Site	Milano		Italy	20133
21	Pfizer Investigational Site	Pisa		Italy	56124
22	Pfizer Investigational Site	Gliwice		Poland	44-101
23	Pfizer Investigational Site	Warszawa		Poland	02-781
24	Pfizer Investigational Site	Pamplona	Navarra	Spain	31008
25	Pfizer Investigational Site	Madrid		Spain	28033
26	Pfizer Investigational Site	Glasgow		United Kingdom	G12 0YN

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: NCT00389441
• Other Study ID Numbers: A4061027
• First Posted: Oct 18, 2006
• Last Update Posted: Nov 25, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Pfizer: VEGFR inhibitor; tyrosine kinase inhibitor; anti-angiogenic; carcinoma; papillary; follicular; medullary; anaplastic
• Additional relevant MeSH terms: Thyroid Neoplasms; Thyroid Diseases; Axitinib

Study Results

Participant Flow

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
Period Title: Overall Study
STARTED	52
COMPLETED	0
NOT COMPLETED	52

Baseline Characteristics

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
Overall Participants	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.6 (12.1)
Sex: Female, Male (Count of Participants)
Female	24 46.2%
Male	28 53.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST). CR: disappearance of all target/non-target lesions and no appearance of new lesions. PR: at least (>=)30 percent(%) decrease in sum of the longest dimensions (LDs) of the target lesions (taking as a reference the baseline sum), without progression of non-target lesions and no appearance of new lesions. Confirmed responses: those persist on repeat imaging study >=4 weeks after initial documentation of response.
Time Frame	Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all participants who were enrolled in the study and received at least 1 dose of study treatment.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
Measure Participants	52
Number (95% Confidence Interval) [percentage of participants]	34.6 66.5%

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS: Time in weeks from the start of study treatment to first documentation of objective disease progression or to death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of first dose of study treatment plus 1) divided by 7. Progression is defined using RECIST, as >=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD since start of study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time Frame	Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were enrolled in the study and received at least 1 dose of study treatment.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
Measure Participants	52
Median (95% Confidence Interval) [weeks]	70.14

3. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame	Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up)

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 continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
Measure Participants	18
Median (95% Confidence Interval) [weeks]	74.71

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Time in weeks 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) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time Frame	Baseline to death due to any cause or at least 2 year after the first dose for the last participant

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were enrolled in the study and received at least 1 dose of study treatment.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
Measure Participants	52
Median (95% Confidence Interval) [weeks]	118.43

5. Secondary Outcome

Title	Change From Baseline in MD Anderson Symptom Assessment Inventory (MDASI) Symptom Severity Score
Description	Symptom severity score is comprised of average of 13 MDASI core items (pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting, numbness or tingling). Participants were asked to rate severity of each symptom at their worst in last 24 hours; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Total average score range: 0 to 10. Lower scores indicated better outcome.
Time Frame	Baseline, Cycle 1 Day 15 (C1D15), C2D1, C2D15, thereafter D1 of each cycle up to 28 days after last dose (follow-up)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were enrolled in the study and received at least 1 dose of study treatment. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies participants evaluable at each time point.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
Measure Participants	49
Baseline (n= 49)	1.66 (1.301)
Change at C1D15 (n= 40)	0.18 (1.158)
Change at C2D1 (n= 42)	0.43 (1.274)
Change at C2D15 (n= 37)	0.52 (1.407)
Change at C3D1 (n= 43)	0.53 (1.602)
Change at C4D1 (n= 39)	0.58 (1.199)
Change at C5D1 (n= 36)	0.69 (1.550)
Change at C6D1 (n= 36)	0.53 (1.484)
Change at C7D1 (n= 29)	0.40 (1.344)
Change at C8D1 (n= 28)	0.44 (1.395)
Change at C9D1 (n= 27)	0.56 (1.516)
Change at C10D1 (n= 25)	0.59 (1.494)
Change at C11D1 (n= 25)	0.63 (1.669)
Change at C12D1 (n= 24)	0.59 (1.584)
Change at C13D1 (n= 24)	0.60 (1.281)
Change at C14D1 (n= 24)	0.59 (1.476)
Change at C15D1 (n= 24)	0.76 (1.654)
Change at C16D1 (n= 23)	0.81 (1.911)
Change at C17D1 (n= 20)	0.73 (1.816)
Change at C18D1 (n= 20)	0.60 (1.729)
Change at C19D1 (n= 18)	0.40 (1.201)
Change at C20D1 (n= 16)	0.50 (0.864)
Change at C21D1 (n= 16)	0.84 (1.094)
Change at C22D1 (n= 15)	0.61 (0.970)
Change at C23D1 (n= 14)	0.87 (1.086)
Change at C24D1 (n= 11)	1.05 (0.990)
Change at C25D1 (n= 11)	0.87 (1.016)
Change at C26D1 (n= 9)	1.15 (0.960)
Change at C27D1 (n= 9)	1.19 (1.244)
Change at C28D1 (n= 10)	0.95 (1.291)
Change at C29D1 (n= 10)	0.98 (1.080)
Change at C30D1 (n= 10)	1.03 (0.970)
Change at C31D1 (n= 9)	1.14 (1.100)
Change at C32D1 (n= 9)	1.44 (1.058)
Change at C33D1 (n= 9)	1.32 (1.233)
Change at C34D1 (n= 8)	1.54 (1.366)
Change at C35D1 (n= 6)	1.29 (1.233)
Change at C36D1 (n= 6)	1.27 (1.610)
Change at C37D1 (n= 5)	1.48 (1.347)
Change at C38D1 (n= 5)	1.27 (1.117)
Change at C39D1 (n= 5)	1.49 (1.288)
Change at C40D1 (n= 5)	1.47 (1.176)
Change at C41D1 (n= 5)	1.48 (1.267)
Change at C42D1 (n= 5)	1.59 (1.312)
Change at C43D1 (n= 5)	1.59 (1.259)
Change at C44D1 (n= 5)	1.42 (1.258)
Change at C45D1 (n= 4)	1.49 (1.349)
Change at C46D1 (n= 4)	1.73 (1.425)
Change at C47D1 (n= 4)	1.70 (1.543)
Change at C48D1 (n= 3)	1.90 (1.377)
Change at C49D1 (n= 3)	2.26 (1.554)
Change at C50D1 (n= 3)	2.38 (1.425)
Change at C51D1 (n= 3)	2.46 (1.533)
Change at C52D1 (n= 1)	3.38 (NA)
Change at C53D1 (n= 1)	3.54 (NA)
Change at C54D1 (n= 1)	3.00 (NA)
Change at C55D1 (n= 1)	3.38 (NA)
Change at C56D1 (n= 1)	3.15 (NA)
Change at C57D1 (n= 1)	3.62 (NA)
Change at C58D1 (n= 1)	3.23 (NA)
Change at C59D1 (n= 1)	3.08 (NA)
Change at C60D1 (n= 1)	3.85 (NA)
Change at C61D1 (n= 1)	3.31 (NA)
Change at C62D1 (n= 1)	3.46 (NA)
Change at follow-up (n= 12)	0.37 (0.939)

6. Secondary Outcome

Title	Change From Baseline in MD Anderson Symptom Assessment Inventory (MDASI) Symptom Interference Score
Description	Symptom interference score is comprised of average of 6 function items from MDASI core (general activity, mood, work, relations with others, walking, and enjoyment of life). Participants were asked to rate how much symptoms have interfered in last 24 hours; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Total average score range: 0 to 10. Lower scores indicated better outcome.
Time Frame	Baseline, Cycle 1 Day 15 (C1D15), C2D1, C2D15, thereafter D1 of each cycle up to 28 days after last dose (follow-up)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were enrolled in the study and received at least 1 dose of study treatment. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure and 'n' signifies participants evaluable at each time point.

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
Measure Participants	48
Baseline (n= 48)	2.24 (2.193)
Change at C1D15 (n= 40)	-0.05 (2.161)
Change at C2D1 (n= 41)	0.28 (2.763)
Change at C2D15 (n= 36)	0.67 (2.403)
Change at C3D1 (n= 42)	0.46 (2.669)
Change at C4D1 (n= 37)	0.47 (2.311)
Change at C5D1 (n= 36)	0.50 (2.377)
Change at C6D1 (n= 36)	0.65 (2.605)
Change at C7D1 (n= 29)	0.19 (2.386)
Change at C8D1 (n= 28)	0.22 (2.242)
Change at C9D1 (n= 27)	0.46 (2.450)
Change at C10D1 (n= 25)	0.35 (2.386)
Change at C11D1 (n= 25)	0.51 (2.784)
Change at C12D1 (n= 23)	0.32 (2.593)
Change at C13D1 (n= 24)	0.42 (2.346)
Change at C14D1 (n= 24)	0.42 (2.624)
Change at C15D1 (n= 24)	0.69 (2.902)
Change at C16D1 (n= 23)	0.73 (3.179)
Change at C17D1 (n= 20)	0.26 (2.920)
Change at C18D1 (n= 20)	0.35 (2.638)
Change at C19D1 (n= 18)	-0.18 (2.497)
Change at C20D1 (n= 15)	0.30 (2.124)
Change at C21D1 (n= 15)	0.50 (1.954)
Change at C22D1 (n= 14)	0.32 (1.979)
Change at C23D1 (n= 14)	0.95 (1.615)
Change at C24D1 (n= 11)	0.77 (1.844)
Change at C25D1 (n= 11)	0.65 (1.699)
Change at C26D1 (n= 9)	1.04 (1.681)
Change at C27D1 (n= 9)	0.81 (2.463)
Change at C28D1 (n= 28)	0.67 (1.956)
Change at C29D1 (n= 29)	0.88 (1.926)
Change at C30D1 (n= 30)	1.03 (1.846)
Change at C31D1 (n= 9)	1.19 (1.910)
Change at C32D1 (n= 9)	1.52 (1.870)
Change at C33D1 (n= 9)	1.07 (1.972)
Change at C34D1 (n= 8)	1.81 (1.846)
Change at C35D1 (n= 6)	1.17 (1.517)
Change at C36D1 (n= 6)	0.97 (1.572)
Change at C37D1 (n= 5)	1.40 (1.782)
Change at C38D1 (n= 5)	1.23 (1.521)
Change at C39D1 (n= 5)	1.50 (1.453)
Change at C40D1 (n= 5)	1.83 (1.889)
Change at C41D1 (n= 5)	1.53 (1.746)
Change at C42D1 (n= 5)	1.67 (1.637)
Change at C43D1 (n= 5)	1.31 (1.267)
Change at C44D1 (n= 5)	1.34 (1.345)
Change at C45D1 (n= 4)	1.50 (1.694)
Change at C46D1 (n= 4)	2.17 (2.113)
Change at C47D1 (n= 4)	1.63 (1.950)
Change at C48D1 (n= 3)	2.00 (1.041)
Change at C49D1 (n= 3)	2.56 (1.798)
Change at C50D1 (n= 3)	0.22 (1.206)
Change at C51D1 (n= 3)	2.44 (1.251)
Change at C52D1 (n= 1)	3.33 (NA)
Change at C53D1 (n= 1)	3.33 (NA)
Change at C54D1 (n= 1)	3.33 (NA)
Change at C55D1 (n= 1)	3.50 (NA)
Change at C56D1 (n= 1)	3.50 (NA)
Change at C57D1 (n= 1)	4.50 (NA)
Change at C58D1 (n= 1)	3.67 (NA)
Change at C59D1 (n= 1)	3.33 (NA)
Change at C60D1 (n= 1)	4.83 (NA)
Change at C61D1 (n= 1)	3.33 (NA)
Change at C62D1 (n= 1)	4.00 (NA)
Change at follow-up (n= 12)	0.32 (2.396)

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 continuously in 28-day cycles until tumor progression, unmanageable toxicity, or withdrawal of consent occurred. Dose was increased (to 7 mg or 10 mg twice daily) or decreased (to 3 mg or 2 mg twice daily) based on the tolerability.
All Cause Mortality
	Axitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Axitinib
	Affected / at Risk (%)	# Events
Total	22/52 (42.3%)
Cardiac disorders
Cardiac failure congestive	1/52 (1.9%)
Hypertensive heart disease	1/52 (1.9%)
Myocardial infarction	1/52 (1.9%)
Myocardial ischaemia	1/52 (1.9%)
Gastrointestinal disorders
Haematemesis	1/52 (1.9%)
Oral pain	1/52 (1.9%)
Pancreatitis	1/52 (1.9%)
General disorders
Chest pain	1/52 (1.9%)
Disease progression	2/52 (3.8%)
Fatigue	3/52 (5.8%)
Immune system disorders
Hypersensitivity	1/52 (1.9%)
Infections and infestations
Appendicitis	1/52 (1.9%)
Upper respiratory tract infection	1/52 (1.9%)
Injury, poisoning and procedural complications
Fracture	1/52 (1.9%)
Investigations
Weight decreased	2/52 (3.8%)
Musculoskeletal and connective tissue disorders
Flank pain	1/52 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	1/52 (1.9%)
Nervous system disorders
Cerebral ischaemia	1/52 (1.9%)
Monoplegia	1/52 (1.9%)
Neuropathy peripheral	1/52 (1.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/52 (5.8%)
Hydrothorax	1/52 (1.9%)
Laryngeal obstruction	1/52 (1.9%)
Respiratory failure	1/52 (1.9%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/52 (1.9%)
Vascular disorders
Arteriosclerosis	1/52 (1.9%)
Jugular vein thrombosis	1/52 (1.9%)
Other (Not Including Serious) Adverse Events
	Axitinib
	Affected / at Risk (%)	# Events
Total	52/52 (100%)
Blood and lymphatic system disorders
Anaemia	3/52 (5.8%)
Leukocytosis	1/52 (1.9%)
Leukopenia	1/52 (1.9%)
Lymphadenopathy	1/52 (1.9%)
Lymphopenia	1/52 (1.9%)
Neutropenia	1/52 (1.9%)
Paratracheal lymphadenopathy	1/52 (1.9%)
Thrombocytopenia	1/52 (1.9%)
Cardiac disorders
Atrial thrombosis	1/52 (1.9%)
Sinus bradycardia	1/52 (1.9%)
Sinus tachycardia	1/52 (1.9%)
Tachycardia	1/52 (1.9%)
Congenital, familial and genetic disorders
Phimosis	1/52 (1.9%)
Ear and labyrinth disorders
Ear pain	1/52 (1.9%)
Hypoacusis	1/52 (1.9%)
Tinnitus	1/52 (1.9%)
Vertigo	1/52 (1.9%)
Endocrine disorders
Hyperparathyroidism	1/52 (1.9%)
Hyperparathyroidism secondary	1/52 (1.9%)
Hypothyroidism	3/52 (5.8%)
Eye disorders
Cataract	1/52 (1.9%)
Conjunctival haemorrhage	1/52 (1.9%)
Conjunctivitis	2/52 (3.8%)
Diplopia	1/52 (1.9%)
Eye swelling	1/52 (1.9%)
Lacrimation increased	1/52 (1.9%)
Orbital oedema	1/52 (1.9%)
Periorbital oedema	1/52 (1.9%)
Vision blurred	1/52 (1.9%)
Vitreous floaters	1/52 (1.9%)
Gastrointestinal disorders
Abdominal discomfort	1/52 (1.9%)
Abdominal distension	2/52 (3.8%)
Abdominal pain	5/52 (9.6%)
Abdominal pain upper	8/52 (15.4%)
Barrett's oesophagus	1/52 (1.9%)
Chapped lips	1/52 (1.9%)
Colitis	1/52 (1.9%)
Colonic polyp	1/52 (1.9%)
Constipation	7/52 (13.5%)
Diarrhoea	31/52 (59.6%)
Dry mouth	4/52 (7.7%)
Dyspepsia	2/52 (3.8%)
Dysphagia	2/52 (3.8%)
Gastrooesophageal reflux disease	1/52 (1.9%)
Gingival bleeding	2/52 (3.8%)
Glossodynia	1/52 (1.9%)
Haematochezia	3/52 (5.8%)
Haemorrhoids	1/52 (1.9%)
Mouth ulceration	1/52 (1.9%)
Nausea	14/52 (26.9%)
Odynophagia	2/52 (3.8%)
Oral pain	1/52 (1.9%)
Proctitis	2/52 (3.8%)
Rectal haemorrhage	1/52 (1.9%)
Stomatitis	6/52 (11.5%)
Tongue ulceration	2/52 (3.8%)
Toothache	2/52 (3.8%)
Vomiting	7/52 (13.5%)
General disorders
Asthenia	4/52 (7.7%)
Chest discomfort	1/52 (1.9%)
Chest pain	3/52 (5.8%)
Facial pain	1/52 (1.9%)
Fatigue	23/52 (44.2%)
Feeling cold	2/52 (3.8%)
Gait disturbance	2/52 (3.8%)
Mucosal inflammation	10/52 (19.2%)
Oedema peripheral	4/52 (7.7%)
Pain	3/52 (5.8%)
Pyrexia	4/52 (7.7%)
Hepatobiliary disorders
Cholecystitis	1/52 (1.9%)
Cholelithiasis	2/52 (3.8%)
Infections and infestations
Anal abscess	1/52 (1.9%)
Bronchitis	1/52 (1.9%)
Candidiasis	1/52 (1.9%)
Dermatitis infected	1/52 (1.9%)
Fungal infection	1/52 (1.9%)
Gastroenteritis	1/52 (1.9%)
Herpes simplex ophthalmic	1/52 (1.9%)
Herpes zoster	1/52 (1.9%)
Influenza	5/52 (9.6%)
Laryngitis	1/52 (1.9%)
Lung infection	1/52 (1.9%)
Nasopharyngitis	4/52 (7.7%)
Otitis externa	1/52 (1.9%)
Otitis media	1/52 (1.9%)
Parotitis	1/52 (1.9%)
Pharyngitis	2/52 (3.8%)
Pneumonia	1/52 (1.9%)
Sinusitis	1/52 (1.9%)
Subcutaneous abscess	1/52 (1.9%)
Tonsillitis	1/52 (1.9%)
Tooth abscess	1/52 (1.9%)
Upper respiratory tract infection	4/52 (7.7%)
Urinary tract infection	1/52 (1.9%)
Viral infection	1/52 (1.9%)
Injury, poisoning and procedural complications
Contusion	1/52 (1.9%)
Excoriation	1/52 (1.9%)
Fall	1/52 (1.9%)
Hand fracture	1/52 (1.9%)
Joint dislocation	1/52 (1.9%)
Overdose	2/52 (3.8%)
Post procedural haemorrhage	3/52 (5.8%)
Procedural pain	1/52 (1.9%)
Investigations
Alanine aminotransferase	1/52 (1.9%)
Alanine aminotransferase increased	1/52 (1.9%)
Aspartate aminotransferase	1/52 (1.9%)
Aspartate aminotransferase increased	2/52 (3.8%)
Blood alkaline phosphatase increased	1/52 (1.9%)
Blood bilirubin increased	1/52 (1.9%)
Blood cholesterol increased	1/52 (1.9%)
Blood creatinine increased	3/52 (5.8%)
Blood lactate dehydrogenase increased	2/52 (3.8%)
Blood phosphorus increased	1/52 (1.9%)
Blood pressure decreased	1/52 (1.9%)
Blood pressure diastolic increased	1/52 (1.9%)
Blood pressure increased	4/52 (7.7%)
Blood thyroid stimulating hormone decreased	1/52 (1.9%)
Blood thyroid stimulating hormone increased	3/52 (5.8%)
Crystal urine present	1/52 (1.9%)
Gamma-glutamyltransferase increased	1/52 (1.9%)
Haematocrit increased	1/52 (1.9%)
Haemoglobin increased	5/52 (9.6%)
Platelet count decreased	1/52 (1.9%)
Protein urine present	2/52 (3.8%)
Thyroglobulin increased	1/52 (1.9%)
Thyroxine increased	2/52 (3.8%)
Weight decreased	18/52 (34.6%)
Metabolism and nutrition disorders
Decreased appetite	19/52 (36.5%)
Dehydration	1/52 (1.9%)
Gout	1/52 (1.9%)
Hypercholesterolaemia	2/52 (3.8%)
Hyperglycaemia	2/52 (3.8%)
Hyperkalaemia	1/52 (1.9%)
Hypoalbuminaemia	2/52 (3.8%)
Hypocalcaemia	4/52 (7.7%)
Hypokalaemia	2/52 (3.8%)
Hyponatraemia	1/52 (1.9%)
Malnutrition	1/52 (1.9%)
Vitamin D deficiency	2/52 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/52 (13.5%)
Back pain	9/52 (17.3%)
Bone pain	2/52 (3.8%)
Mastication disorder	1/52 (1.9%)
Muscle spasms	3/52 (5.8%)
Musculoskeletal chest pain	2/52 (3.8%)
Musculoskeletal pain	3/52 (5.8%)
Myalgia	3/52 (5.8%)
Neck pain	2/52 (3.8%)
Osteoporosis	1/52 (1.9%)
Pain in extremity	16/52 (30.8%)
Pain in jaw	2/52 (3.8%)
Spinal osteoarthritis	1/52 (1.9%)
Spondylolisthesis	1/52 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipofibroma	1/52 (1.9%)
Pyogenic granuloma	1/52 (1.9%)
Nervous system disorders
Ataxia	1/52 (1.9%)
Burning sensation	1/52 (1.9%)
Disturbance in attention	1/52 (1.9%)
Dizziness	4/52 (7.7%)
Dysgeusia	1/52 (1.9%)
Headache	10/52 (19.2%)
Hypoaesthesia	2/52 (3.8%)
Lethargy	1/52 (1.9%)
Motor dysfunction	1/52 (1.9%)
Neuralgia	1/52 (1.9%)
Neuropathy peripheral	4/52 (7.7%)
Paraesthesia	7/52 (13.5%)
Somnolence	2/52 (3.8%)
Syncope	1/52 (1.9%)
Thrombotic cerebral infarction	1/52 (1.9%)
Tremor	1/52 (1.9%)
Psychiatric disorders
Anxiety	1/52 (1.9%)
Depression	5/52 (9.6%)
Insomnia	5/52 (9.6%)
Mood altered	1/52 (1.9%)
Sleep disorder	2/52 (3.8%)
Renal and urinary disorders
Dysuria	1/52 (1.9%)
Haematuria	2/52 (3.8%)
Pollakiuria	1/52 (1.9%)
Proteinuria	6/52 (11.5%)
Urinary retention	1/52 (1.9%)
Urinary tract pain	2/52 (3.8%)
Reproductive system and breast disorders
Amenorrhoea	1/52 (1.9%)
Dyspareunia	1/52 (1.9%)
Erectile dysfunction	2/52 (3.8%)
Menstrual disorder	2/52 (3.8%)
Pelvic pain	1/52 (1.9%)
Vulvovaginal dryness	1/52 (1.9%)
Respiratory, thoracic and mediastinal disorders
Cough	11/52 (21.2%)
Dry throat	1/52 (1.9%)
Dysphonia	7/52 (13.5%)
Dyspnoea	12/52 (23.1%)
Dyspnoea exertional	1/52 (1.9%)
Epistaxis	1/52 (1.9%)
Haemoptysis	6/52 (11.5%)
Oropharyngeal discomfort	1/52 (1.9%)
Oropharyngeal pain	6/52 (11.5%)
Pleural effusion	2/52 (3.8%)
Rhinitis allergic	2/52 (3.8%)
Tachypnoea	1/52 (1.9%)
Throat irritation	1/52 (1.9%)
Skin and subcutaneous tissue disorders
Alopecia	7/52 (13.5%)
Dermal cyst	1/52 (1.9%)
Dermatitis	2/52 (3.8%)
Dry skin	5/52 (9.6%)
Eczema	3/52 (5.8%)
Erythema	1/52 (1.9%)
Hair colour changes	1/52 (1.9%)
Hyperkeratosis	1/52 (1.9%)
Nail disorder	1/52 (1.9%)
Nail pigmentation	1/52 (1.9%)
Palmar-plantar erythrodysaesthesia syndrome	6/52 (11.5%)
Petechiae	1/52 (1.9%)
Pruritus	4/52 (7.7%)
Rash	8/52 (15.4%)
Skin disorder	1/52 (1.9%)
Skin exfoliation	1/52 (1.9%)
Skin fissures	1/52 (1.9%)
Skin haemorrhage	1/52 (1.9%)
Skin lesion	1/52 (1.9%)
Skin reaction	1/52 (1.9%)
Skin swelling	1/52 (1.9%)
Skin ulcer	1/52 (1.9%)
Surgical and medical procedures
Mole excision	1/52 (1.9%)
Vascular disorders
Hypertension	28/52 (53.8%)
Hypertensive crisis	1/52 (1.9%)
Peripheral artery thrombosis	1/52 (1.9%)
Thrombosis	1/52 (1.9%)

Limitations/Caveats

[Not Specified]

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.