AG-013736 In Combination With Docetaxel Versus Docetaxel Alone For Patients With Metastatic Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00076024
• Collaborator: (none)
• Enrollment: 174
• Locations: 54
• Arms: 2
• Duration (Months): 57
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary purpose of the study is to determine the time to progression of the combination of study drug (AG-013736) and docetaxel versus docetaxel alone in patients who have not received prior chemotherapy for metastatic breast cancer. The secondary purpose of the study is to determine the dose of study drug that can be given with docetaxel administered on an every 3 week schedule.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Placebo; Drug: Docetaxel; Drug: AG-013736 (axitinib); Drug: Docetaxel	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 174 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study Of AG-013736 In Combination With Docetaxel Versus Docetaxel Alone In Patients With Metastatic Breast Cancer Preceded By A Phase 1 Evaluation Of The Combination
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Other: Docetaxel + Placebo Docetaxel + Placebo	Drug: Placebo; 5 mg twice daily [bid] continuous dosing; Drug: Docetaxel; Standard of care drug administration
Experimental: Docetaxel + AG-013736 Docetaxel + AG-013736	Drug: AG-013736 (axitinib); 5mg twice daily [bid] continuous dosing; Drug: Docetaxel; Standard of care drug administration

Outcome Measures

Primary Outcome Measures

1. Time to Tumor Progression (TTP) [Phase 2 double-blind baseline until tumor progression or death or discontinuation from study treatment, assessed every 9 weeks up to 129 weeks]

   Time in days from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP 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]).

Secondary Outcome Measures

1. Percentage of Participants With Objective Response (OR) for Phase 2 (Double-blind) [Phase 2 double- blind baseline until the date of first documented progression or discontinuation from the study treatment due to any cause, assessed every 9 weeks up to 129 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 response. 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 longest dimensions.

2. Percentage of Participants With Objective Response (OR) for Phase 2 (Open-label) [Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 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 response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

3. Duration of Response (DR) for Phase 2 (Double-blind) [Phase 2 double-blind baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 9 weeks up to 129 weeks]

   Time in days 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 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.

4. Duration of Response (DR) for Phase 2 (Open-label) [Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks]

   Time in days 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 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.

Other Outcome Measures

1. Population Pharmacokinetics of Axitinib (AG-013736) for Phase 2 (Double-blind) [Day 1 (pre-dose), Day 22 and Day 43 and then every 9 weeks up to 129 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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Female patients with histologically/cytologically proven metastatic breast carcinoma (stage IV, or recurrent with local or regional spread or distant metastatic disease)

• Adequate bone marrow, liver, and renal function

Exclusion Criteria:

• Adjuvant chemotherapy given in the past 12 months

• Uncontrolled brain metastases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Tucson	Arizona	United States	85724-5024
2	Pfizer Investigational Site	Tucson	Arizona	United States	85724
3	Pfizer Investigational Site	Berkeley	California	United States	94704
4	Pfizer Investigational Site	Montebello	California	United States	90640
5	Pfizer Investigational Site	Monterey Park	California	United States	91754
6	Pfizer Investigational Site	San Francisco	California	United States	94115
7	Pfizer Investigational Site	San Gabriel	California	United States	91776
8	Pfizer Investigational Site	Whittier	California	United States	90602
9	Pfizer Investigational Site	Jacksonville Beach	Florida	United States	32250
10	Pfizer Investigational Site	Jacksonville	Florida	United States	32204
11	Pfizer Investigational Site	Jacksonville	Florida	United States	32207
12	Pfizer Investigational Site	Jacksonville	Florida	United States	32223
13	Pfizer Investigational Site	Melbourne	Florida	United States	32901
14	Pfizer Investigational Site	Orange Park	Florida	United States	32073
15	Pfizer Investigational Site	Palatka	Florida	United States	32177
16	Pfizer Investigational Site	St. Augustine	Florida	United States	32086
17	Pfizer Investigational Site	Chicago	Illinois	United States	60612
18	Pfizer Investigational Site	Chicago	Illinois	United States	60637
19	Pfizer Investigational Site	Zion	Illinois	United States	60099
20	Pfizer Investigational Site	Boston	Massachusetts	United States	02118
21	Pfizer Investigational Site	Ann Arbor	Michigan	United States	48106
22	Pfizer Investigational Site	Stony Brook	New York	United States	11794
23	Pfizer Investigational Site	Cleveland	Ohio	United States	44195
24	Pfizer Investigational Site	Corvallis	Oregon	United States	97330
25	Pfizer Investigational Site	Edmonton	Alberta	Canada	T6G 1Z2
26	Pfizer Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
27	Pfizer Investigational Site	Montreal	Quebec	Canada	H2L 4M1
28	Pfizer Investigational Site	Novy Jicin		Czech Republic	741 01
29	Pfizer Investigational Site	Praha 8		Czech Republic	180 00
30	Pfizer Investigational Site	Berlin		Germany	10117
31	Pfizer Investigational Site	Essen		Germany	45122
32	Pfizer Investigational Site	Frankfurt		Germany	60590
33	Pfizer Investigational Site	Freiburg		Germany	79106
34	Pfizer Investigational Site	Hamburg		Germany	22081
35	Pfizer Investigational Site	Bangalore	Karnataka	India	560 034
36	Pfizer Investigational Site	Pune	Maharashtra	India	411 004
37	Pfizer Investigational Site	Napoli		Italy	80131
38	Pfizer Investigational Site	Roma		Italy	00128
39	Pfizer Investigational Site	Roma		Italy	00135
40	Pfizer Investigational Site	Roma		Italy	00144
41	Pfizer Investigational Site	Rozzano (Mi)		Italy	20089
42	Pfizer Investigational Site	Taormina, ME		Italy	98039
43	Pfizer Investigational Site	Hospitalet de Llobregat	Barcelona	Spain	08907
44	Pfizer Investigational Site	Sabadell	Barcelona	Spain	08208
45	Pfizer Investigational Site	Girona		Spain	17007
46	Pfizer Investigational Site	Madrid		Spain	28040
47	Pfizer Investigational Site	Madrid		Spain	28041
48	Pfizer Investigational Site	Malaga		Spain	29010
49	Pfizer Investigational Site	Valencia		Spain	46009
50	Pfizer Investigational Site	Valencia		Spain	46010
51	Pfizer Investigational Site	Southampton	Hampshire	United Kingdom	SO16 6YD
52	Pfizer Investigational Site	Rickmansworth	Middlesex	United Kingdom	HA5 2RN
53	Pfizer Investigational Site	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
54	Pfizer Investigational Site	Sheffield	Yorkshire	United Kingdom	S10 2SJ

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: NCT00076024
• Other Study ID Numbers: A4061010
• First Posted: Jan 14, 2004
• Last Update Posted: Jun 26, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Pfizer: metastatic breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Docetaxel; Axitinib

Study Results

Participant Flow

Pre-assignment Detail	Participants who progressed in Docetaxel + Placebo (Phase 2, Double-blind) after consent were eligible to continue to open-label phase. 16 participants crossed-over to open-label phase.

Arm/Group Title	Axitinib + Docetaxel (Phase-1, Lead-in)	Axitinib + Docetaxel (Phase 2, Double-blind)	Docetaxel + Placebo (Phase 2, Double-blind)	Axitinib (Phase 2, Open-label)
Arm/Group Description	Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily (BID) starting from Day 3 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 milligram/square meter (mg/m^2) 1 hour (hr) intravenous (IV) infusion on Day 1 of each cycle, in cycles of 3 weeks.	Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response.	Placebo matched to axitinib (AG-013736) tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response. Participants with disease progression after consent were continued to open-label phase.	Axitinib (AG-013736) 5 mg tablet orally BID continuously in cycles of 4 weeks.
Period Title: Phase 1, Lead-in
STARTED	6	0	0	0
COMPLETED	0	0	0	0
NOT COMPLETED	6	0	0	0
Period Title: Phase 1, Lead-in
STARTED	0	112	56	0
Treated	0	111	56	0
COMPLETED	0	0	0	0
NOT COMPLETED	0	112	56	0
Period Title: Phase 1, Lead-in
STARTED	0	0	0	16
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	0	16

Baseline Characteristics

Arm/Group Title	Axitinib + Docetaxel (Phase 1, Lead-in)	Axitinib + Docetaxel (Phase 2, Double-blind)	Docetaxel + Placebo (Double-blind)	Total
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet orally twice daily BID starting from Day 3 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks.	Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response.	Placebo matched to axitinib (AG-013736) tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response. Participants with disease progression after consent were continued with axitinib (AG-013736) 5 mg tablet orally BID continuously in cycles of 4 weeks.	Total of all reporting groups
Overall Participants	6	112	56	174
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.80 (9.68)	54.10 (10.43)	54.70 (10.12)	54.2 (10.3)
Sex: Female, Male (Count of Participants)
Female	6 100%	112 100%	56 100%	174 100%
Male	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Time to Tumor Progression (TTP)
Description	Time in days from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP 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]).
Time Frame	Phase 2 double-blind baseline until tumor progression or death or discontinuation from study treatment, assessed every 9 weeks up to 129 weeks

Outcome Measure Data

Analysis Population Description

Study population included all randomized participants who had a baseline assessment of disease and the correct histological cancer type.

Arm/Group Title	Axitinib + Docetaxel (Phase 2, Double-blind)	Docetaxel + Placebo (Phase 2, Double-blind)
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response.	Placebo matched to axitinib (AG-013736) tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response. Participants with disease progression after consent were continued to open-label phase.
Measure Participants	112	55
Median (95% Confidence Interval) [days]	247	215

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib + Docetaxel (Phase 2, Double-blind), Docetaxel + Placebo (Phase 2, Double-blind)
	Comments	P-value was calculated using one-sided Log rank test, stratified for estrogen receptor (ER) status (ER-positive or ER-negative/unknown), prior adjuvant chemotherapy (yes or no), and Eastern Cooperative Oncology Group (ECOG) performance status (less than or equal to [=<1] or 2). The stratified Cox proportional hazards model was fitted, using the same stratification variables as above.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.156
	Comments
	Method	Log Rank
	Comments	One-sided log-rank test at alpha = 0.1 significance level was used.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.237
	Confidence Interval	(2-Sided) 95%; 0.819 to 1.867
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR) for Phase 2 (Double-blind)
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 response. 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 longest dimensions.
Time Frame	Phase 2 double- blind baseline until the date of first documented progression or discontinuation from the study treatment due to any cause, assessed every 9 weeks up to 129 weeks

Outcome Measure Data

Analysis Population Description

Study population included all randomized participants who had a baseline assessment of disease and the correct histological cancer type.

Arm/Group Title	Axitinib + Docetaxel (Phase 2, Double-blind)	Docetaxel + Placebo (Phase 2, Double-blind)
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response.	Placebo matched to axitinib (AG-013736) tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response. Participants with disease progression after consent were continued to open-label phase.
Measure Participants	112	55
Number (95% Confidence Interval) [percentage of participants]	41.1 685%	23.6 21.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib + Docetaxel (Phase 2, Double-blind), Docetaxel + Placebo (Phase 2, Double-blind)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	17.4
	Confidence Interval	(2-Sided) 95%; 3.0 to 31.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR) for Phase 2 (Open-label)
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 response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks

Outcome Measure Data

Analysis Population Description

All treated (AT) population included participants from Phase 2 who progressed by RECIST criteria while in the placebo + docetaxel treatment group and had a baseline disease assessment and received at least 1 dose of study medication.

Arm/Group Title	Axitinib (Phase 2, Open-label)
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet orally BID continuously in cycles of 4 weeks.
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	6.3 105%

4. Secondary Outcome

Title	Duration of Response (DR) for Phase 2 (Double-blind)
Description	Time in days 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 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	Phase 2 double-blind baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 9 weeks up to 129 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Axitinib + Docetaxel (Phase 2, Double-blind)	Docetaxel + Placebo (Phase 2, Double-blind)
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response.	Placebo matched to axitinib (AG-013736) tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response. Participants with disease progression after consent were continued to open-label phase.
Measure Participants	46	13
Median (95% Confidence Interval) [days]	211	149

5. Secondary Outcome

Title	Duration of Response (DR) for Phase 2 (Open-label)
Description	Time in days 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 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	Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Axitinib (Phase 2, Open-label)
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet orally BID continuously in cycles of 4 weeks.
Measure Participants	1
Median (95% Confidence Interval) [days]	1.0

6. Other Pre-specified Outcome

Title	Population Pharmacokinetics of Axitinib (AG-013736) for Phase 2 (Double-blind)
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 22 and Day 43 and then every 9 weeks up to 129 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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 + Docetaxel (Phase-1 Lead-in)		Axitinib + Docetaxel (Phase 2, Double-blind)		Docetaxel + Placebo (Phase 2, Double-blind)		Axitinib (Phase 2, Open-label)
Arm/Group Description	Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 3 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks.		Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response.		Placebo matched to axitinib (AG-013736) tablet orally BID starting from Day 1 of Cycle 1, in cycles of 3 weeks. Docetaxel 80 mg/m^2 1 hr IV infusion on Day 1 of each cycle, in cycles of 3 weeks. Treatment was continued until disease progression, intolerable toxicity, or for 2 cycles after complete response. Participants with disease progression after consent were continued to open-label phase.		Axitinib (AG-013736) 5 mg tablet orally BID continuously in cycles of 4 weeks.
All Cause Mortality
	Axitinib + Docetaxel (Phase-1 Lead-in)		Axitinib + Docetaxel (Phase 2, Double-blind)		Docetaxel + Placebo (Phase 2, Double-blind)		Axitinib (Phase 2, Open-label)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Axitinib + Docetaxel (Phase-1 Lead-in)		Axitinib + Docetaxel (Phase 2, Double-blind)		Docetaxel + Placebo (Phase 2, Double-blind)		Axitinib (Phase 2, Open-label)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		54/111 (48.6%)		17/56 (30.4%)		2/16 (12.5%)
Blood and lymphatic system disorders
Agranulocytosis	0/6 (0%)		0/111 (0%)		1/56 (1.8%)		0/16 (0%)
Febrile neutropenia	1/6 (16.7%)		9/111 (8.1%)		3/56 (5.4%)		0/16 (0%)
Neutropenia	0/6 (0%)		10/111 (9%)		3/56 (5.4%)		0/16 (0%)
Cardiac disorders
Arrhythmia supraventricular	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Left ventricular dysfunction	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Palpitations	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Pericardial effusion	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Restrictive cardiomyopathy	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Endocrine disorders
Hypothyroidism	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Eye disorders
Angle closure glaucoma	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Diplopia	0/6 (0%)		0/111 (0%)		1/56 (1.8%)		0/16 (0%)
Uveitis	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Gastrointestinal disorders
Abdominal distension	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Abdominal pain	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Diarrhoea	0/6 (0%)		4/111 (3.6%)		1/56 (1.8%)		0/16 (0%)
Duodenal ulcer	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Dysphagia	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Haemorrhoids	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Nausea	0/6 (0%)		4/111 (3.6%)		2/56 (3.6%)		0/16 (0%)
Odynophagia	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Stomatitis	1/6 (16.7%)		5/111 (4.5%)		0/56 (0%)		0/16 (0%)
Volvulus	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Vomiting	0/6 (0%)		4/111 (3.6%)		2/56 (3.6%)		0/16 (0%)
General disorders
Asthenia	0/6 (0%)		3/111 (2.7%)		0/56 (0%)		0/16 (0%)
Chest pain	0/6 (0%)		2/111 (1.8%)		0/56 (0%)		0/16 (0%)
Haemorrhagic cyst	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Mucosal inflammation	0/6 (0%)		3/111 (2.7%)		0/56 (0%)		0/16 (0%)
Pyrexia	0/6 (0%)		6/111 (5.4%)		1/56 (1.8%)		0/16 (0%)
Thrombosis in device	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Hepatobiliary disorders
Cholecystitis	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Cholecystitis acute	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Hyperbilirubinaemia	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Infections and infestations
Anal abscess	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Breast abscess	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Bronchopneumonia	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Catheter site infection	0/6 (0%)		2/111 (1.8%)		0/56 (0%)		0/16 (0%)
Clostridial infection	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Enterobacter infection	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Groin abscess	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Herpes zoster	0/6 (0%)		0/111 (0%)		1/56 (1.8%)		0/16 (0%)
Infection	0/6 (0%)		1/111 (0.9%)		1/56 (1.8%)		0/16 (0%)
Influenza	0/6 (0%)		0/111 (0%)		1/56 (1.8%)		0/16 (0%)
Lower respiratory tract infection	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Neutropenic sepsis	0/6 (0%)		1/111 (0.9%)		1/56 (1.8%)		0/16 (0%)
Oral candidiasis	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Pneumonia	0/6 (0%)		2/111 (1.8%)		0/56 (0%)		0/16 (0%)
Respiratory tract infection	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Urinary tract infection	0/6 (0%)		0/111 (0%)		1/56 (1.8%)		0/16 (0%)
Investigations
Gamma-glutamyltransferase increased	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Neutrophil count decreased	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Weight decreased	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
White blood cell count decreased	0/6 (0%)		0/111 (0%)		1/56 (1.8%)		0/16 (0%)
Metabolism and nutrition disorders
Dehydration	0/6 (0%)		4/111 (3.6%)		1/56 (1.8%)		0/16 (0%)
Hyponatraemia	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Malignant pleural effusion	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Metastases to liver	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Metastases to meninges	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Metastases to nervous system	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Nervous system disorders
Lethargy	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Nervous system disorder	0/6 (0%)		0/111 (0%)		1/56 (1.8%)		0/16 (0%)
Radiculopathy	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Syncope	0/6 (0%)		0/111 (0%)		2/56 (3.6%)		0/16 (0%)
Convulsion	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/6 (0%)		2/111 (1.8%)		1/56 (1.8%)		0/16 (0%)
Epistaxis	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Haemothorax	0/6 (0%)		0/111 (0%)		1/56 (1.8%)		0/16 (0%)
Nasal septum perforation	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Pleural effusion	0/6 (0%)		0/111 (0%)		2/56 (3.6%)		0/16 (0%)
Pneumonitis	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Pneumothorax	0/6 (0%)		1/111 (0.9%)		1/56 (1.8%)		0/16 (0%)
Pulmonary embolism	0/6 (0%)		3/111 (2.7%)		0/56 (0%)		0/16 (0%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Palmar-plantar erythrodysaesthesia syndrome	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Vascular disorders
Capillary leak syndrome	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Deep vein thrombosis	0/6 (0%)		2/111 (1.8%)		0/56 (0%)		0/16 (0%)
Hypertension	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Hypotension	0/6 (0%)		1/111 (0.9%)		0/56 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Axitinib + Docetaxel (Phase-1 Lead-in)		Axitinib + Docetaxel (Phase 2, Double-blind)		Docetaxel + Placebo (Phase 2, Double-blind)		Axitinib (Phase 2, Open-label)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		111/111 (100%)		56/56 (100%)		12/16 (75%)
Blood and lymphatic system disorders
Anaemia	2/6 (33.3%)		10/111 (9%)		13/56 (23.2%)		1/16 (6.3%)
Febrile neutropenia	0/6 (0%)		9/111 (8.1%)		0/56 (0%)		0/16 (0%)
Leukopenia	0/6 (0%)		15/111 (13.5%)		12/56 (21.4%)		0/16 (0%)
Neutropenia	4/6 (66.7%)		39/111 (35.1%)		20/56 (35.7%)		0/16 (0%)
Eye disorders
Conjunctivitis	0/6 (0%)		15/111 (13.5%)		4/56 (7.1%)		0/16 (0%)
Lacrimation increased	3/6 (50%)		33/111 (29.7%)		11/56 (19.6%)		0/16 (0%)
Gastrointestinal disorders
Abdominal pain	4/6 (66.7%)		26/111 (23.4%)		5/56 (8.9%)		2/16 (12.5%)
Abdominal pain upper	0/6 (0%)		8/111 (7.2%)		6/56 (10.7%)		2/16 (12.5%)
Constipation	2/6 (33.3%)		37/111 (33.3%)		12/56 (21.4%)		2/16 (12.5%)
Diarrhoea	5/6 (83.3%)		69/111 (62.2%)		24/56 (42.9%)		4/16 (25%)
Dry mouth	0/6 (0%)		9/111 (8.1%)		4/56 (7.1%)		1/16 (6.3%)
Dyspepsia	3/6 (50%)		16/111 (14.4%)		6/56 (10.7%)		0/16 (0%)
Dysphagia	2/6 (33.3%)		6/111 (5.4%)		0/56 (0%)		1/16 (6.3%)
Gastrooesophageal reflux disease	0/6 (0%)		7/111 (6.3%)		0/56 (0%)		0/16 (0%)
Glossodynia	3/6 (50%)		8/111 (7.2%)		4/56 (7.1%)		3/16 (18.8%)
Haemorrhoids	1/6 (16.7%)		8/111 (7.2%)		0/56 (0%)		0/16 (0%)
Nausea	5/6 (83.3%)		54/111 (48.6%)		19/56 (33.9%)		10/16 (62.5%)
Oral pain	4/6 (66.7%)		11/111 (9.9%)		5/56 (8.9%)		3/16 (18.8%)
Rectal haemorrhage	0/6 (0%)		8/111 (7.2%)		0/56 (0%)		0/16 (0%)
Stomatitis	3/6 (50%)		47/111 (42.3%)		6/56 (10.7%)		1/16 (6.3%)
Vomiting	4/6 (66.7%)		42/111 (37.8%)		17/56 (30.4%)		5/16 (31.3%)
General disorders
Asthenia	0/6 (0%)		39/111 (35.1%)		10/56 (17.9%)		1/16 (6.3%)
Chest pain	0/6 (0%)		6/111 (5.4%)		7/56 (12.5%)		1/16 (6.3%)
Chills	1/6 (16.7%)		8/111 (7.2%)		6/56 (10.7%)		1/16 (6.3%)
Fatigue	4/6 (66.7%)		52/111 (46.8%)		24/56 (42.9%)		7/16 (43.8%)
Mucosal inflammation	3/6 (50%)		42/111 (37.8%)		12/56 (21.4%)		1/16 (6.3%)
Oedema peripheral	1/6 (16.7%)		18/111 (16.2%)		13/56 (23.2%)		1/16 (6.3%)
Pain	1/6 (16.7%)		7/111 (6.3%)		9/56 (16.1%)		0/16 (0%)
Pyrexia	1/6 (16.7%)		22/111 (19.8%)		10/56 (17.9%)		0/16 (0%)
Immune system disorders
Seasonal allergy	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Cellulitis	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Infected sebaceous cyst	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Oral candidiasis	2/6 (33.3%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Rhinitis	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Tooth abscess	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Tooth infection	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Vulvovaginal candidiasis	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Vulvovaginal mycotic infection	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Skin laceration	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Alanine aminotransferase	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Aspartate aminotransferase	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Haemoglobin	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Neutrophil count	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Neutrophil count decreased	2/6 (33.3%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
White blood cell count decreased	2/6 (33.3%)		0/111 (0%)		3/56 (5.4%)		0/16 (0%)
Hypoalbuminaemia	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Pain in jaw	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Dyskinesia	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Hyperaesthesia	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Migraine	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Haematuria	2/6 (33.3%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Micturition urgency	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Urinary incontinence	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Vaginal discharge	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Vaginal haemorrhage	2/6 (33.3%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Vulvovaginal discomfort	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Vulvovaginal pain	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Nasal congestion	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Nasal discomfort	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Productive cough	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Rhinitis allergic	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Sputum discoloured	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Upper-airway cough syndrome	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Wheezing	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Hirsutism	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Onychalgia	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Pain of skin	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Rash erythematous	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Skin reaction	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Umbilical erythema	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Urticaria	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Flushing	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Hypotension	1/6 (16.7%)		0/111 (0%)		5/56 (8.9%)		1/16 (6.3%)
Eye pain	0/6 (0%)		0/111 (0%)		3/56 (5.4%)		0/16 (0%)
Abdominal distension	0/6 (0%)		0/111 (0%)		3/56 (5.4%)		0/16 (0%)
Catheter site pain	0/6 (0%)		0/111 (0%)		4/56 (7.1%)		0/16 (0%)
Face oedema	0/6 (0%)		0/111 (0%)		4/56 (7.1%)		0/16 (0%)
Oedema	0/6 (0%)		0/111 (0%)		5/56 (8.9%)		0/16 (0%)
Dyspnoea exertional	0/6 (0%)		0/111 (0%)		3/56 (5.4%)		0/16 (0%)
Pleural effusion	0/6 (0%)		0/111 (0%)		5/56 (8.9%)		0/16 (0%)
Hot flush	0/6 (0%)		0/111 (0%)		4/56 (7.1%)		0/16 (0%)
Lymphoedema	0/6 (0%)		0/111 (0%)		6/56 (10.7%)		0/16 (0%)
Lymphadenopathy	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Eyelid oedema	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Hyperchlorhydria	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Oral discomfort	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Retching	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Catheter site erythema	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Chest discomfort	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Influenza like illness	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Influenza	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Sinusitis	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Transaminases increased	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Flank pain	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Groin pain	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Muscle fatigue	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Balance disorder	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Facial neuralgia	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Sinus headache	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Proteinuria	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Postnasal drip	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Eczema	0/6 (0%)		0/111 (0%)		0/56 (0%)		2/16 (12.5%)
Hyperkeratosis	0/6 (0%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Infections and infestations
Nasopharyngitis	0/6 (0%)		8/111 (7.2%)		6/56 (10.7%)		0/16 (0%)
Upper respiratory tract infection	1/6 (16.7%)		7/111 (6.3%)		4/56 (7.1%)		0/16 (0%)
Urinary tract infection	3/6 (50%)		14/111 (12.6%)		4/56 (7.1%)		0/16 (0%)
Investigations
Weight decreased	2/6 (33.3%)		16/111 (14.4%)		0/56 (0%)		1/16 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	3/6 (50%)		36/111 (32.4%)		13/56 (23.2%)		5/16 (31.3%)
Dehydration	4/6 (66.7%)		12/111 (10.8%)		0/56 (0%)		1/16 (6.3%)
Hyperglycaemia	0/6 (0%)		6/111 (5.4%)		0/56 (0%)		1/16 (6.3%)
Hypokalaemia	0/6 (0%)		6/111 (5.4%)		0/56 (0%)		1/16 (6.3%)
Hyponatraemia	0/6 (0%)		6/111 (5.4%)		0/56 (0%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/6 (50%)		21/111 (18.9%)		10/56 (17.9%)		1/16 (6.3%)
Back pain	1/6 (16.7%)		21/111 (18.9%)		11/56 (19.6%)		2/16 (12.5%)
Bone pain	1/6 (16.7%)		18/111 (16.2%)		11/56 (19.6%)		2/16 (12.5%)
Muscle spasms	0/6 (0%)		6/111 (5.4%)		0/56 (0%)		1/16 (6.3%)
Muscular weakness	2/6 (33.3%)		10/111 (9%)		3/56 (5.4%)		2/16 (12.5%)
Musculoskeletal chest pain	2/6 (33.3%)		6/111 (5.4%)		3/56 (5.4%)		1/16 (6.3%)
Musculoskeletal pain	2/6 (33.3%)		9/111 (8.1%)		5/56 (8.9%)		2/16 (12.5%)
Myalgia	2/6 (33.3%)		22/111 (19.8%)		7/56 (12.5%)		0/16 (0%)
Neck pain	0/6 (0%)		6/111 (5.4%)		0/56 (0%)		0/16 (0%)
Pain in extremity	0/6 (0%)		25/111 (22.5%)		10/56 (17.9%)		6/16 (37.5%)
Nervous system disorders
Dizziness	1/6 (16.7%)		22/111 (19.8%)		6/56 (10.7%)		3/16 (18.8%)
Dysgeusia	4/6 (66.7%)		25/111 (22.5%)		10/56 (17.9%)		1/16 (6.3%)
Headache	3/6 (50%)		27/111 (24.3%)		13/56 (23.2%)		6/16 (37.5%)
Hypoaesthesia	1/6 (16.7%)		9/111 (8.1%)		3/56 (5.4%)		0/16 (0%)
Neuropathy peripheral	4/6 (66.7%)		14/111 (12.6%)		8/56 (14.3%)		0/16 (0%)
Paraesthesia	0/6 (0%)		13/111 (11.7%)		5/56 (8.9%)		0/16 (0%)
Peripheral sensory neuropathy	2/6 (33.3%)		16/111 (14.4%)		6/56 (10.7%)		1/16 (6.3%)
Psychiatric disorders
Anxiety	2/6 (33.3%)		9/111 (8.1%)		5/56 (8.9%)		0/16 (0%)
Depression	0/6 (0%)		7/111 (6.3%)		4/56 (7.1%)		1/16 (6.3%)
Insomnia	0/6 (0%)		20/111 (18%)		7/56 (12.5%)		0/16 (0%)
Renal and urinary disorders
Dysuria	1/6 (16.7%)		8/111 (7.2%)		3/56 (5.4%)		0/16 (0%)
Pollakiuria	0/6 (0%)		7/111 (6.3%)		0/56 (0%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/6 (50%)		18/111 (16.2%)		14/56 (25%)		2/16 (12.5%)
Dysphonia	1/6 (16.7%)		10/111 (9%)		4/56 (7.1%)		4/16 (25%)
Dyspnoea	1/6 (16.7%)		23/111 (20.7%)		10/56 (17.9%)		5/16 (31.3%)
Epistaxis	3/6 (50%)		30/111 (27%)		10/56 (17.9%)		0/16 (0%)
Oropharyngeal pain	3/6 (50%)		20/111 (18%)		8/56 (14.3%)		1/16 (6.3%)
Rhinorrhoea	0/6 (0%)		7/111 (6.3%)		5/56 (8.9%)		0/16 (0%)
Skin and subcutaneous tissue disorders
Alopecia	4/6 (66.7%)		56/111 (50.5%)		30/56 (53.6%)		1/16 (6.3%)
Blister	2/6 (33.3%)		7/111 (6.3%)		0/56 (0%)		0/16 (0%)
Dry skin	1/6 (16.7%)		14/111 (12.6%)		7/56 (12.5%)		2/16 (12.5%)
Erythema	0/6 (0%)		9/111 (8.1%)		4/56 (7.1%)		0/16 (0%)
Nail discolouration	0/6 (0%)		6/111 (5.4%)		0/56 (0%)		0/16 (0%)
Nail disorder	5/6 (83.3%)		23/111 (20.7%)		14/56 (25%)		0/16 (0%)
Onycholysis	0/6 (0%)		8/111 (7.2%)		0/56 (0%)		0/16 (0%)
Palmar-plantar erythrodysaesthesia syndrome	1/6 (16.7%)		11/111 (9.9%)		0/56 (0%)		0/16 (0%)
Pruritus	0/6 (0%)		13/111 (11.7%)		5/56 (8.9%)		0/16 (0%)
Rash	2/6 (33.3%)		26/111 (23.4%)		7/56 (12.5%)		2/16 (12.5%)
Skin exfoliation	0/6 (0%)		10/111 (9%)		0/56 (0%)		0/16 (0%)
Vascular disorders
Hypertension	4/6 (66.7%)		36/111 (32.4%)		3/56 (5.4%)		8/16 (50%)
Bradycardia	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Tachycardia	1/6 (16.7%)		0/111 (0%)		3/56 (5.4%)		2/16 (12.5%)
Dacryostenosis acquired	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Glaucoma	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Keratitis	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Ocular hyperaemia	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Vision blurred	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Abdominal discomfort	2/6 (33.3%)		0/111 (0%)		0/56 (0%)		1/16 (6.3%)
Dental caries	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Flatulence	2/6 (33.3%)		0/111 (0%)		3/56 (5.4%)		0/16 (0%)
Haemorrhoidal haemorrhage	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Odynophagia	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Toothache	1/6 (16.7%)		0/111 (0%)		4/56 (7.1%)		1/16 (6.3%)
Axillary pain	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)
Irritability	1/6 (16.7%)		0/111 (0%)		0/56 (0%)		0/16 (0%)

Limitations/Caveats

Analysis of TTP (Phase 2, Double-blind) was performed with both discontinuation due to lack of efficacy (LOE) considered a progression and not considered a progression event. Latter was considered primary analysis and former a sensitivity analysis.

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.