SU011248 In The Treatment Of Patients With Bevacizumab (Avastin)-Refractory Metastatic Renal Cell Carcinoma

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00089648
• Collaborator: (none)
• Enrollment: 61
• Locations: 11
• Arm: 1
• Duration (Months): 39
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to test whether sunitinib (SU011248) has activity and is safe in patients with renal cell carcinoma (RCC) who have failed prior therapy with bevacizumab (Avastin) -based treatment.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell	Drug: Sunitinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study Of SU011248 In The Treatment Of Patients With Bevacizumab-Refractory Metastatic Renal Cell Carcinoma
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Sunitinib; 50 mg orally daily for 4 weeks followed by 2 weeks off treatment for approximately 1 year or until disease progression/unacceptable toxicity; after completion of 1 year, pts with clinical benefit can continue the study treatment in a separate continuation protocol; Other Names: SUTENT, SU011248,

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST) [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up]

   Objective disease response = subjects with confirmed complete response (CR) or partial response (PR) according to RECIST. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

Secondary Outcome Measures

1. Time to Tumor Progression (TTP) [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up]

   TTP was defined as the time from the date of first dose of study medication to the date of the first documentation of tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.

2. Duration of Response (DR) [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up]

   DR was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to to any cause that occurred within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was only calculated for the subgroup of subjects with a confirmed objective response. DR was calculated as [the end date for DR minus first CR or PR that was subsequently confirmed +1]/7. Kaplan-Meier method was used.

3. Overall Survival (OS) [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up]

   OS was defined as the time from start of study treatment to date of death due to any cause. OS (in weeks) was calculated as [date of death minus first dose date +1]/7. For a subject not expiring, the OS time was censored on the last date of known contact that they were known to be alive. Subjects lacking data beyond the day of the first dose had their OS times censored at 1 day. Kaplan-Meier method was used.

4. Progression Free Survival (PFS) [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up]

   PFS was defined as the time from start of study medication to first documentation of objective tumor progression or to death due to any cause that occurred on treatment including within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.

5. Trough Plasma Concentrations (Cmin) of Sunitinib [Day 28 of Cycle 1 to Cycle 4]

6. Trough Plasma Concentrations (Cmin) of SU012662 [Day 28 of Cycle 1 to Cycle 4]

7. Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662) [Day 28 of Cycle 1 to Cycle 4]

8. Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A) [Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1)]

   Plasma concentrations of VEGF-A that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.

9. Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) [Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1)]

   Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.

10. Plasma Concentration of Placental Growth Factor (PlGF) [Cycle 1 (Days 1, 14, and 28)]

    Plasma concentrations of PlGF that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.

11. Plasma Concentration of VEGF-C [Cycle 1 (Days 1, 14, and 28)]

    Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.

12. Plasma Concentration of Soluble VEGF Receptor-2(sVEGFR-2) [1 year]

    Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were to have been analyzed by ELISA analysis; however, no data were collected.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically proven renal cell carcinoma of clear cell histology with metastases

• Evidence of measurable disease

• Radiographic evidence of disease progression during or within 3 months of completion of bevacizumab-based treatment

• Prior radical or partial nephrectomy

Exclusion Criteria:

• Prior treatment with any other anti-angiogenic therapy other than bevacizumab

• Prior systemic treatment for RCC > 2 regimens

• History of or known brain metastases

• Serious acute or chronic illness or recent history of significant cardiac abnormality

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Duarte	California	United States	91010
2	Pfizer Investigational Site	Pasadena	California	United States	91105
3	Pfizer Investigational Site	San Francisco	California	United States	94115
4	Pfizer Investigational Site	Chicago	Illinois	United States	60637-1460
5	Pfizer Investigational Site	Boston	Massachusetts	United States	02114
6	Pfizer Investigational Site	Boston	Massachusetts	United States	02115
7	Pfizer Investigational Site	Boston	Massachusetts	United States	02215
8	Pfizer Investigational Site	Durham	North Carolina	United States	27710
9	Pfizer Investigational Site	Cleveland	Ohio	United States	44195
10	Pfizer Investigational Site	Nashville	Tennessee	United States	37232-5536
11	Pfizer Investigational Site	Dallas	Texas	United States	75246

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.

• ClinicalTrials.gov Identifier: NCT00089648
• Other Study ID Numbers: A6181039
• First Posted: Aug 11, 2004
• Last Update Posted: Jan 12, 2010
• Last Verified: Jan 1, 2010

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Period Title: Overall Study
STARTED	61
COMPLETED	20
NOT COMPLETED	41

Baseline Characteristics

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Overall Participants	61
Age, Customized (participants) [Number]
< 65 years	43 70.5%
> = 65 years	18 29.5%
Sex: Female, Male (Count of Participants)
Female	27 44.3%
Male	34 55.7%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Objective disease response = subjects with confirmed complete response (CR) or partial response (PR) according to RECIST. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT)=all subjects enrolled in the study that received at least 1 dose of study medication.

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Number [participants]	14 23%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Response Rate (ORR) (percent)
	Estimated Value	23.0
	Confidence Interval	() 95%; 13.2 to 35.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	ORR=proportion of subjects with confirmed CR or PR, relative to total number of subjects who received at least 1 dose of study medication, were refractory to bevacizumab, had a baseline disease assessment and had the correct histological cancer type.

2. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	TTP was defined as the time from the date of first dose of study medication to the date of the first documentation of tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT. 20 subjects were censored.

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Median (95% Confidence Interval) [weeks]	30.4

3. Secondary Outcome

Title	Duration of Response (DR)
Description	DR was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to to any cause that occurred within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was only calculated for the subgroup of subjects with a confirmed objective response. DR was calculated as [the end date for DR minus first CR or PR that was subsequently confirmed +1]/7. Kaplan-Meier method was used.
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT subjects (i.e, all subjects enrolled in the study that received at least 1 dose of study medication) who had a confirmed CR or PR. 14 subjects who had a response were analyzed for DR.

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Median (95% Confidence Interval) [weeks]	36.1

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from start of study treatment to date of death due to any cause. OS (in weeks) was calculated as [date of death minus first dose date +1]/7. For a subject not expiring, the OS time was censored on the last date of known contact that they were known to be alive. Subjects lacking data beyond the day of the first dose had their OS times censored at 1 day. Kaplan-Meier method was used.
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Median (95% Confidence Interval) [weeks]	47.1

5. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time from start of study medication to first documentation of objective tumor progression or to death due to any cause that occurred on treatment including within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT. 20 subjects were censored.

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Median (Full Range) [weeks]	30.4

6. Secondary Outcome

Title	Trough Plasma Concentrations (Cmin) of Sunitinib
Time Frame	Day 28 of Cycle 1 to Cycle 4

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	59
Cycle 1, Day 28 (n=20)	52.05
Cycle 2, Day 28 (n=23)	43.50
Cycle 3, Day 28 (n=10)	46.10
Cycle 4, Day 28 (n=16)	44.90

7. Secondary Outcome

Title	Trough Plasma Concentrations (Cmin) of SU012662
Time Frame	Day 28 of Cycle 1 to Cycle 4

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	59
Cycle 1, Day 28 (n=20)	30.50
Cycle 2, Day 28 (n=23)	21.40
Cycle 3, Day 28 (n=10)	22.10
Cycle 4, Day 28 (n=16)	23.75

8. Secondary Outcome

Title	Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662)
Time Frame	Day 28 of Cycle 1 to Cycle 4

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	59
Cycle 1, Day 28 (n=20)	85.40
Cycle 2, Day 28 (n=23)	66.60
Cycle 3, Day 28 (n=10)	68.40
Cycle 4, Day 28 (n=16)	68.15

9. Secondary Outcome

Title	Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A)
Description	Plasma concentrations of VEGF-A that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Time Frame	Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Cycle 1, Day 1 (Baseline) (n=59)	567.4
Cycle 1, Day 14 (n=57)	1320.6
Cycle 1, Day 28 (n=55)	1212.3
Cycle 2, Day 1 (n=54)	316.2

10. Secondary Outcome

Title	Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
Description	Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Time Frame	Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Cycle 1, Day 1 (Baseline) (n=54)	54170.4
Cycle 1, Day 14 (n=32)	37747.0
Cycle 1, Day 28 (n=22)	46891.0
Cycle 2, Day 1 (n=46)	51280.0

11. Secondary Outcome

Title	Plasma Concentration of Placental Growth Factor (PlGF)
Description	Plasma concentrations of PlGF that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Time Frame	Cycle 1 (Days 1, 14, and 28)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Cycle 1, Day 1 (Baseline) (n=37)	55.0
Cycle 1, Day 14 (n=58)	146.1
Cycle 1, Day 28 (n=53)	137.9

12. Secondary Outcome

Title	Plasma Concentration of VEGF-C
Description	Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Time Frame	Cycle 1 (Days 1, 14, and 28)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	61
Cycle 1, Day 1 (Baseline) (n=57)	833.0
Cycle 1, Day 14 (n=57)	688.0
Cycle 1, Day 28 (n=54)	566.5

13. Secondary Outcome

Title	Plasma Concentration of Soluble VEGF Receptor-2(sVEGFR-2)
Description	Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were to have been analyzed by ELISA analysis; however, no data were collected.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
Measure Participants	0

Adverse Events

Arm/Group Title	Sunitinib
Arm/Group Description	50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle).
All Cause Mortality
	Sunitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	30/61 (49.2%)
Blood and lymphatic system disorders
Anaemia	2/61 (3.3%)
Cardiac disorders
Angina pectoris	1/61 (1.6%)
Atrial fibrillation	1/61 (1.6%)
Pericardial effusion	1/61 (1.6%)
Endocrine disorders
Adrenal insufficiency	2/61 (3.3%)
Hypothyroidism	1/61 (1.6%)
Gastrointestinal disorders
Nausea	4/61 (6.6%)
Vomiting	4/61 (6.6%)
Abdominal pain	2/61 (3.3%)
Ascites	2/61 (3.3%)
Diarrhoea	2/61 (3.3%)
Gastrointestinal haemorrhage	2/61 (3.3%)
Abdominal distension	1/61 (1.6%)
Abdominal pain lower	1/61 (1.6%)
Haemorrhoidal haemorrhage	1/61 (1.6%)
General disorders
Disease progression	5/61 (8.2%)
Fatigue	4/61 (6.6%)
Pyrexia	2/61 (3.3%)
Chest pain	1/61 (1.6%)
Generalised oedema	1/61 (1.6%)
Oedema	1/61 (1.6%)
Pain	1/61 (1.6%)
Infections and infestations
Diverticulitis	2/61 (3.3%)
Pneumonia	2/61 (3.3%)
Wound infection	2/61 (3.3%)
Abdominal abscess	1/61 (1.6%)
Appendicitis	1/61 (1.6%)
Injury, poisoning and procedural complications
Accidental overdose	1/61 (1.6%)
Investigations
Activated partial thromboplastin time prolonged	1/61 (1.6%)
Electrocardiogram QT corrected interval prolonged	1/61 (1.6%)
Metabolism and nutrition disorders
Dehydration	3/61 (4.9%)
Anorexia	2/61 (3.3%)
Hyponatraemia	1/61 (1.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/61 (1.6%)
Back pain	1/61 (1.6%)
Buttock pain	1/61 (1.6%)
Muscular weakness	1/61 (1.6%)
Pain in extremity	1/61 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	1/61 (1.6%)
Nervous system disorders
Cerebral haemorrhage	1/61 (1.6%)
Depressed level of consciousness	1/61 (1.6%)
Loss of consciousness	1/61 (1.6%)
Spinal cord compression	1/61 (1.6%)
Syncope	1/61 (1.6%)
Psychiatric disorders
Confusional state	1/61 (1.6%)
Psychotic disorder	1/61 (1.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	5/61 (8.2%)
Pleural effusion	2/61 (3.3%)
Haemoptysis	1/61 (1.6%)
Pulmonary embolism	1/61 (1.6%)
Skin and subcutaneous tissue disorders
Angioneurotic oedema	1/61 (1.6%)
Vascular disorders
Deep vein thrombosis	2/61 (3.3%)
Other (Not Including Serious) Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	60/61 (98.4%)
Blood and lymphatic system disorders
Anaemia	16/61 (26.2%)
Thrombocytopenia	4/61 (6.6%)
Endocrine disorders
Hypothyroidism	14/61 (23%)
Eye disorders
Lacrimation increased	5/61 (8.2%)
Gastrointestinal disorders
Abdominal distension	4/61 (6.6%)
Abdominal pain	10/61 (16.4%)
Cheilitis	8/61 (13.1%)
Constipation	25/61 (41%)
Diarrhoea	42/61 (68.9%)
Dry mouth	6/61 (9.8%)
Dyspepsia	20/61 (32.8%)
Eructation	4/61 (6.6%)
Flatulence	7/61 (11.5%)
Gastrooesophageal reflux disease	10/61 (16.4%)
Glossodynia	4/61 (6.6%)
Haemorrhoids	7/61 (11.5%)
Nausea	37/61 (60.7%)
Stomatitis	28/61 (45.9%)
Vomiting	29/61 (47.5%)
General disorders
Chest pain	8/61 (13.1%)
Chills	12/61 (19.7%)
Fatigue	54/61 (88.5%)
Mucosal inflammation	21/61 (34.4%)
Oedema peripheral	20/61 (32.8%)
Pain	5/61 (8.2%)
Pyrexia	13/61 (21.3%)
Infections and infestations
Sinusitis	8/61 (13.1%)
Upper respiratory tract infection	5/61 (8.2%)
Urinary tract infection	10/61 (16.4%)
Excoriation	4/61 (6.6%)
Investigations
Alanine aminotransferase increased	6/61 (9.8%)
Aspartate aminotransferase increased	8/61 (13.1%)
Blood creatinine increased	9/61 (14.8%)
Blood glucose increased	4/61 (6.6%)
Blood phosphorus decreased	4/61 (6.6%)
Blood uric acid increased	4/61 (6.6%)
Ejection fraction decreased	7/61 (11.5%)
Haemoglobin decreased	5/61 (8.2%)
Lipase increased	5/61 (8.2%)
Neutrophil count decreased	8/61 (13.1%)
Platelet count decreased	5/61 (8.2%)
Weight decreased	11/61 (18%)
Weight increased	5/61 (8.2%)
White blood cell count decreased	7/61 (11.5%)
Metabolism and nutrition disorders
Anorexia	37/61 (60.7%)
Dehydration	9/61 (14.8%)
Hyperglycaemia	6/61 (9.8%)
Hyperuricaemia	4/61 (6.6%)
Hypokalaemia	5/61 (8.2%)
Hyponatraemia	6/61 (9.8%)
Hypophosphataemia	4/61 (6.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/61 (13.1%)
Back pain	14/61 (23%)
Flank pain	4/61 (6.6%)
Muscle spasms	4/61 (6.6%)
Muscular weakness	4/61 (6.6%)
Musculoskeletal chest pain	4/61 (6.6%)
Musculoskeletal pain	5/61 (8.2%)
Myalgia	8/61 (13.1%)
Neck pain	5/61 (8.2%)
Pain in extremity	20/61 (32.8%)
Nervous system disorders
Dizziness	12/61 (19.7%)
Dysgeusia	34/61 (55.7%)
Headache	14/61 (23%)
Peripheral sensory neuropathy	4/61 (6.6%)
Psychiatric disorders
Anxiety	6/61 (9.8%)
Confusional state	4/61 (6.6%)
Insomnia	13/61 (21.3%)
Respiratory, thoracic and mediastinal disorders
Cough	20/61 (32.8%)
Dysphonia	5/61 (8.2%)
Dyspnoea	22/61 (36.1%)
Epistaxis	10/61 (16.4%)
Haemoptysis	4/61 (6.6%)
Nasal congestion	4/61 (6.6%)
Pharyngolaryngeal pain	9/61 (14.8%)
Rhinitis allergic	5/61 (8.2%)
Skin and subcutaneous tissue disorders
Alopecia	4/61 (6.6%)
Dry skin	12/61 (19.7%)
Exfoliative rash	5/61 (8.2%)
Hair colour changes	8/61 (13.1%)
Palmar-plantar erythrodysaesthesia syndrome	22/61 (36.1%)
Periorbital oedema	8/61 (13.1%)
Pruritus	5/61 (8.2%)
Rash	12/61 (19.7%)
Skin discolouration	24/61 (39.3%)
Skin reaction	11/61 (18%)
Vascular disorders
Hypertension	20/61 (32.8%)
Hypotension	5/61 (8.2%)

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 < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.