A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00121836
• Collaborator: (none)
• Enrollment: 109
• Locations: 57
• Arm: 1
• Duration (Months): 42
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This single-arm study was designed to evaluate the efficacy and safety of oral Xeloda plus intravenous Avastin as first-line treatment in women with metastatic breast cancer. Patients received Xeloda 1000 mg/m² orally (PO) twice daily (BID) on Days 1-15, and Avastin 15 mg intravenously (IV) on Day 1 of each 3-week cycle. The anticipated time on study treatment was until disease progression or unacceptable toxicity. The target sample size was <100 individuals.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Capecitabine; Drug: Bevacizumab	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study of Xeloda Plus Avastin at Time of Disease Progression in Treatment-naïve Women With HER2-negative Metastatic Breast Cancer
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Capecitabine; 1000 mg/m² PO BID on Days 1-15 of each 3-week cycle; Other Names: Xeloda ; Drug: Bevacizumab; 15 mg IV on Day 1 of each 3-week cycle; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Overall Survival [approximately 505 days (Median Time to Death)]

   Overall survival was defined as the time from date of first treatment dose (Day 1) to date of death, across the study phases regardless of the cause of death

Secondary Outcome Measures

1. Number of Subjects With Adverse Events [Throughout study]

   The secondary outcome measure was to evaluate the safety profile, including a summary of adverse events (AEs) assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Intensity of AEs were graded according to NCI CTCAE version 3.0 on a 5-point scale: Grade 1=Mild Discomfort, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life Threatening/Disabling and Grade 5=Death. An SAE was defined as any experience that suggested a significant hazard,contraindication, side effect, or precaution.

2. Premature Withdrawal From Study Due to Adverse Events [Throughout study]

   The secondary outcome measure was to evaluate the safety profile, including a summary of premature withdrawals due to adverse events occurring in more than 1 patient in either study group, by system organ class.

3. Number of Participants With Marked Laboratory Abnormalities [until progressive disease or for up to 3 years]

   The secondary outcome measure was to evaluate the safety profile, including a summary of marked laboratory abnormalities in >= 5% of patients. n=number of participants with the laboratory measure,Number=number of participants with the abnormality. Laboratory values were flagged as Low(L) or High(H) if they were below the lower limit or above the upper limit of Roche standard reference range, respectively. Marked laboratory abnormalities (flagged as HH and LL) were defined as those values that were outside the Roche marked reference range and showed a clinically relevant change from baseline.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Women >=18 years of age

• HER2-negative metastatic breast cancer

• Previous adjuvant chemotherapy or hormonal treatment

• =1 measurable target lesion

Exclusion Criteria:

• Previous treatment with chemotherapy, an anti-angiogenic agent, or a biologic therapy for advanced or metastatic cancer

• Radiation therapy within 4 weeks of study treatment start or insufficient recovery from the effects of prior radiation therapy

• Central nervous system metastases

• Other malignancy within last 5 years, except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix

• Serious concurrent infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35022
2		Birmingham	Alabama	United States	35205
3		Birmingham	Alabama	United States	35209
4		Birmingham	Alabama	United States	35211
5		Birmingham	Alabama	United States	35213
6		Birmingham	Alabama	United States	35235
7		Burbank	California	United States	91505
8		Glendale	California	United States	91204
9		Glendale	California	United States	91206
10		Los Angeles	California	United States	90057
11		San Diego	California	United States	92121
12		Farmington	Connecticut	United States	06030
13		Bonita Springs	Florida	United States	34135
14		Boynton Beach	Florida	United States	33435
15		Bradenton	Florida	United States	34209
16		Cape Coral	Florida	United States	33990
17		Fort Myers	Florida	United States	33901
18		Fort Myers	Florida	United States	33908
19		Naples	Florida	United States	34102
20		Naples	Florida	United States	34119
21		Port Charlotte	Florida	United States	33980
22		Sarasota	Florida	United States	34232
23		Sarasota	Florida	United States	34236
24		Venice	Florida	United States	34292
25		Atlanta	Georgia	United States	30341
26		Augusta	Georgia	United States	30901
27		Tucker	Georgia	United States	30084
28		Chicago	Illinois	United States	60611
29		Indianapolis	Indiana	United States	46202
30		Indianapolis	Indiana	United States	46219
31		Waterloo	Iowa	United States	50702
32		Scarborough	Maine	United States	04074
33		Prince Frederick	Maryland	United States	20678
34		Lansing	Michigan	United States	48909
35		Kansas City	Missouri	United States	64064
36		Kansas City	Missouri	United States	64111
37		Kansas City	Missouri	United States	64131
38		Kansas City	Missouri	United States	64154
39		Kansas City	Missouri	United States	66112
40		Kansas City	Missouri	United States	66210
41		Lincoln	Nebraska	United States	68510
42		Omaha	Nebraska	United States	68114
43		Las Vegas	Nevada	United States	89106
44		Brick	New Jersey	United States	08724
45		Neptune	New Jersey	United States	07754
46		Red Bank	New Jersey	United States	07701
47		Rochester	New York	United States	14642
48		Hickory	North Carolina	United States	28602
49		Canton	Ohio	United States	44718
50		Oklahoma City	Oklahoma	United States	73112
51		Beaufort	South Carolina	United States	29902
52		Charleston	South Carolina	United States	29406
53		Florence	South Carolina	United States	29506
54		Hilton Head Island	South Carolina	United States	29926
55		Sumter	South Carolina	United States	29150
56		Abingdon	Virginia	United States	24211
57		Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Study Report Synopsis

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00121836
• Other Study ID Numbers: ML18527
• First Posted: Jul 21, 2005
• Last Update Posted: Apr 27, 2011
• Last Verified: Apr 1, 2011

• Additional relevant MeSH terms: Breast Neoplasms; Bevacizumab; Capecitabine

Study Results

Participant Flow

Arm/Group Title	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev
Arm/Group Description	First Study Treatment Phase: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle. Second Study Treatment Phase: Paclitaxel 80 mg/m² 60-minute IV infusion (with appropriate premedication), Days 1, 8 and 15 of each 4-week cycle (28 days). Substitution of paclitaxel with docetaxel was not allowed. Vinorelbine 25 mg/m² IV infusion over 10-20 minutes, Days 1, 8, and 15 of each 4-week cycle. Bevacizumab 10 mg/kg IV infusion, Days 1 and 15 of each 4-week cycle.
Period Title: Overall Study
STARTED	109
COMPLETED	54
NOT COMPLETED	55

Baseline Characteristics

Arm/Group Title	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev
Arm/Group Description	First Study Treatment Phase: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle. Second Study Treatment Phase: Paclitaxel 80 mg/m² 60-minute IV infusion (with appropriate premedication), Days 1, 8 and 15 of each 4-week cycle (28 days). Substitution of paclitaxel with docetaxel was not allowed. Vinorelbine 25 mg/m² IV infusion over 10-20 minutes, Days 1, 8, and 15 of each 4-week cycle. Bevacizumab 10 mg/kg IV infusion, Days 1 and 15 of each 4-week cycle.
Overall Participants	109
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.7 (12.03)
Sex: Female, Male (Count of Participants)
Female	109 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from date of first treatment dose (Day 1) to date of death, across the study phases regardless of the cause of death
Time Frame	approximately 505 days (Median Time to Death)

Outcome Measure Data

Analysis Population Description

109 patients (pts) received study drug in the First Study Treatment Phase. 54 pts withdrew prematurely, and 54 pts proceeded to the Second Study Treatment Phase. All 54 pts who proceeded to the Second Study Treatment Phase withdrew during that phase. 1 pt continued treatment in the First Study Treatment Phase and completed 3 years of follow-up.

Arm/Group Title	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev
Arm/Group Description	First Study Treatment Phase: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle. Second Study Treatment Phase: Paclitaxel 80 mg/m² 60-minute IV infusion (with appropriate premedication), Days 1, 8 and 15 of each 4-week cycle (28 days). Substitution of paclitaxel with docetaxel was not allowed. Vinorelbine 25 mg/m² IV infusion over 10-20 minutes, Days 1, 8, and 15 of each 4-week cycle. Bevacizumab 10 mg/kg IV infusion, Days 1 and 15 of each 4-week cycle.
Measure Participants	109
Median (95% Confidence Interval) [Days]	505

2. Secondary Outcome

Title	Number of Subjects With Adverse Events
Description	The secondary outcome measure was to evaluate the safety profile, including a summary of adverse events (AEs) assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Intensity of AEs were graded according to NCI CTCAE version 3.0 on a 5-point scale: Grade 1=Mild Discomfort, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life Threatening/Disabling and Grade 5=Death. An SAE was defined as any experience that suggested a significant hazard,contraindication, side effect, or precaution.
Time Frame	Throughout study

Outcome Measure Data

Analysis Population Description

109 patients (pts) received study drug in the First Study Treatment Phase. 54 pts withdrew prematurely, and 54 pts proceeded to the Second Study Treatment Phase. All 54 pts who proceeded to the Second Study Treatment Phase withdrew during that phase. 1 pt continued treatment in the First Study Treatment Phase and completed 3 years of follow-up.

Arm/Group Title	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev	First Study Treatment Phase Only
Arm/Group Description	First Study Treatment Phase: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle. Second Study Treatment Phase: Paclitaxel 80 mg/m² 60-minute IV infusion (with appropriate premedication), Days 1, 8 and 15 of each 4-week cycle (28 days). Substitution of paclitaxel with docetaxel was not allowed. Vinorelbine 25 mg/m² IV infusion over 10-20 minutes, Days 1, 8, and 15 of each 4-week cycle. Bevacizumab 10 mg/kg IV infusion, Days 1 and 15 of each 4-week cycle.	Capecitabine+Bevacizumab: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle.
Measure Participants	109	55
At least 1 adverse event (AE)	108 99.1%	54 NaN
At least 1 treatment-related AE	104 95.4%	51 NaN
At least 1 Grade 3 or 4 AE	82 75.2%	41 NaN
At least 1 serious adverse event (SAE)	39 35.8%	22 NaN
At least 1 AE causing withdrawal	37 33.9%	25 NaN

3. Secondary Outcome

Title	Premature Withdrawal From Study Due to Adverse Events
Description	The secondary outcome measure was to evaluate the safety profile, including a summary of premature withdrawals due to adverse events occurring in more than 1 patient in either study group, by system organ class.
Time Frame	Throughout study

Outcome Measure Data

Analysis Population Description

109 patients (pts) received study drug in the First Study Treatment Phase. 54 pts withdrew prematurely, and 54 pts proceeded to the Second Study Treatment Phase. All 54 pts who proceeded to the Second Study Treatment Phase withdrew during that phase. 1 pt continued treatment in the First Study Treatment Phase and completed 3 years of follow-up.

Arm/Group Title	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev	First Study Treatment Phase Only
Arm/Group Description	First Study Treatment Phase: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle. Second Study Treatment Phase: Paclitaxel 80 mg/m² 60-minute IV infusion (with appropriate premedication), Days 1, 8 and 15 of each 4-week cycle (28 days). Substitution of paclitaxel with docetaxel was not allowed. Vinorelbine 25 mg/m² IV infusion over 10-20 minutes, Days 1, 8, and 15 of each 4-week cycle. Bevacizumab 10 mg/kg IV infusion, Days 1 and 15 of each 4-week cycle.	Capecitabine+Bevacizumab: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle.
Measure Participants	109	55
All system organ classes	25 22.9%	37 NaN
General disorders, administration site conditions	4 3.7%	7 NaN
Musculoskeletal and connective tissue disorders	2 1.8%	6 NaN
Respiratory, thoracic and mediastinal disorders	2 1.8%	5 NaN
Renal and urinary disorders	2 1.8%	2 NaN

4. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormalities
Description	The secondary outcome measure was to evaluate the safety profile, including a summary of marked laboratory abnormalities in >= 5% of patients. n=number of participants with the laboratory measure,Number=number of participants with the abnormality. Laboratory values were flagged as Low(L) or High(H) if they were below the lower limit or above the upper limit of Roche standard reference range, respectively. Marked laboratory abnormalities (flagged as HH and LL) were defined as those values that were outside the Roche marked reference range and showed a clinically relevant change from baseline.
Time Frame	until progressive disease or for up to 3 years

Outcome Measure Data

Analysis Population Description

109 patients (pts) received study drug in the First Study Treatment Phase. 54 pts withdrew prematurely, and 54 pts proceeded to the Second Study Treatment Phase. All 54 pts who proceeded to the Second Study Treatment Phase withdrew during that phase. 1 pt continued treatment in the First Study Treatment Phase and completed 3 years of follow-up.

Arm/Group Title	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev
Arm/Group Description	First Study Treatment Phase: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle. Second Study Treatment Phase: Paclitaxel 80 mg/m² 60-minute IV infusion (with appropriate premedication), Days 1, 8 and 15 of each 4-week cycle (28 days). Substitution of paclitaxel with docetaxel was not allowed. Vinorelbine 25 mg/m² IV infusion over 10-20 minutes, Days 1, 8, and 15 of each 4-week cycle. Bevacizumab 10 mg/kg IV infusion, Days 1 and 15 of each 4-week cycle.
Measure Participants	109
Hematocrit (fraction) (n=104); Abnormality: Low	16 14.7%
Hemoglobin (g/L) (n=104); Abnormality: Low	18 16.5%
Platelets (10^9/L) (n=104); Abnormality: Low	9 8.3%
Red blood cells (10¹²/L) (n=104); Abnormality: Low	15 13.8%
White blood cells (10^9/L)(n=104); Abnormality:Low	23 21.1%
Neutrophils (10^9/L) (n=92); Abnormality: High	14 12.8%
Neutrophils (10^9/L) (n=92); Abnormality: Low	25 22.9%
Prothrombin time (ratio) (n=36); Abnormality: High	3 2.8%
Aspartate transaminase(U/L)(n=104)Abnormality:High	19 17.4%
Alanine transaminase(U/L)(n=104);Abnormality: High	10 9.2%
Alkaline phosphatase(U/L)(n=104);Abnormality: High	11 10.1%
Direct bilirubin (umol/L) (n=78);Abnormality: High	4 3.7%
Albumin (g/L) (n=104); Abnormality: Low	13 11.9%
Total protein (g/L) (n=104); Abnormality: Low	8 7.3%
Chloride (mmol/L) (n=104); Abnormality: Low	5 4.6%
Calcium (mmol/L) (n=104); Abnormality: Low	10 9.2%
Uric acid (umol/L) (n=94); Abnormality: High	5 4.6%

Adverse Events

Arm/Group Title	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev
Arm/Group Description	First Study Treatment Phase: Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle. Second Study Treatment Phase: Paclitaxel 80 mg/m² 60-minute IV infusion (with appropriate premedication), Days 1, 8 and 15 of each 4-week cycle (28 days). Substitution of paclitaxel with docetaxel was not allowed. Vinorelbine 25 mg/m² IV infusion over 10-20 minutes, Days 1, 8, and 15 of each 4-week cycle. Bevacizumab 10 mg/kg IV infusion, Days 1 and 15 of each 4-week cycle.
All Cause Mortality
	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev
	Affected / at Risk (%)	# Events
Total	39/109 (35.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/109 (0.9%)
Cardiac disorders
Left Ventricular Failure	1/109 (0.9%)
Gastrointestinal disorders
Nausea	3/109 (2.8%)
Vomiting	3/109 (2.8%)
Abdominal Pain	1/109 (0.9%)
Caecitis	1/109 (0.9%)
Diarrhoea	1/109 (0.9%)
Enterovesical Fistula	1/109 (0.9%)
Gastric Ulcer	1/109 (0.9%)
Pancreatitis	1/109 (0.9%)
General disorders
Pain	6/109 (5.5%)
Chest Pain	3/109 (2.8%)
Mucosal Inflammation	2/109 (1.8%)
Fatigue	1/109 (0.9%)
Influenza Like Illness	1/109 (0.9%)
Infections and infestations
Bacterial Sepsis	1/109 (0.9%)
Cellulitis	1/109 (0.9%)
Infection	1/109 (0.9%)
Perirectal Abscess	1/109 (0.9%)
Pneumonia	1/109 (0.9%)
Sepsis	1/109 (0.9%)
Urinary Tract Infection	1/109 (0.9%)
Urosepsis	1/109 (0.9%)
Injury, poisoning and procedural complications
Fall	1/109 (0.9%)
Hip Fracture	1/109 (0.9%)
Scapula Fracture	1/109 (0.9%)
Investigations
Blood Sodium Decreased	1/109 (0.9%)
Haemoglobin Decreased	1/109 (0.9%)
Urine Output Decreased	1/109 (0.9%)
Metabolism and nutrition disorders
Dehydration	5/109 (4.6%)
Decreased Appetite	1/109 (0.9%)
Hypocalcaemia	1/109 (0.9%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	2/109 (1.8%)
Muscular Weakness	1/109 (0.9%)
Musculoskeletal Chest Pain	1/109 (0.9%)
Neck Pain	1/109 (0.9%)
Pathological Fracture	1/109 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Meninges	1/109 (0.9%)
Nervous system disorders
Cerebral Haemorrhage	1/109 (0.9%)
Headache	1/109 (0.9%)
Lethargy	1/109 (0.9%)
Renal and urinary disorders
Renal Failure	1/109 (0.9%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	3/109 (2.8%)
Dyspnoea	1/109 (0.9%)
Hypoxia	1/109 (0.9%)
Pleural Effusion	1/109 (0.9%)
Vascular disorders
Haemorrhage	1/109 (0.9%)
Phlebitis	1/109 (0.9%)
Other (Not Including Serious) Adverse Events
	Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev
	Affected / at Risk (%)	# Events
Total	103/109 (94.5%)
Blood and lymphatic system disorders
Neutropenia	24/109 (22%)
Anaemia	21/109 (19.3%)
Eye disorders
Lacrimation Increased	7/109 (6.4%)
Gastrointestinal disorders
Diarrhoea	66/109 (60.6%)
Nausea	66/109 (60.6%)
Constipation	41/109 (37.6%)
Vomiting	36/109 (33%)
Dyspepsia	25/109 (22.9%)
Stomatitis	15/109 (13.8%)
Abdominal Pain	12/109 (11%)
Abdominal Pain Upper	8/109 (7.3%)
Abdominal Distension	7/109 (6.4%)
Oral Pain	6/109 (5.5%)
General disorders
Fatigue	68/109 (62.4%)
Mucosal Inflammation	30/109 (27.5%)
Pyrexia	21/109 (19.3%)
Pain	19/109 (17.4%)
Asthenia	13/109 (11.9%)
Oedema Peripheral	13/109 (11.9%)
Chills	6/109 (5.5%)
Infections and infestations
Sinusitis	15/109 (13.8%)
Upper Respiratory Tract Infection	13/109 (11.9%)
Urinary Tract Infection	12/109 (11%)
Investigations
Weight Decreased	12/109 (11%)
Aspartate Aminotransferase Increased	8/109 (7.3%)
Alanine Aminotransferase Increased	7/109 (6.4%)
Neutrophil Count Decreased	7/109 (6.4%)
Metabolism and nutrition disorders
Anorexia	35/109 (32.1%)
Dehydration	8/109 (7.3%)
Hyperglycaemia	6/109 (5.5%)
Hypokalaemia	6/109 (5.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	29/109 (26.6%)
Pain in Extremity	28/109 (25.7%)
Back Pain	21/109 (19.3%)
Musculoskeletal Pain	17/109 (15.6%)
Bone Pain	9/109 (8.3%)
Neck Pain	8/109 (7.3%)
Musculoskeletal Chest Pain	6/109 (5.5%)
Myalgia	6/109 (5.5%)
Nervous system disorders
Headache	32/109 (29.4%)
Dysgeusia	27/109 (24.8%)
Neuropathy Peripheral	20/109 (18.3%)
Dizziness	14/109 (12.8%)
Peripheral Sensory Neuropathy	6/109 (5.5%)
Psychiatric disorders
Insomnia	22/109 (20.2%)
Depression	21/109 (19.3%)
Anxiety	12/109 (11%)
Renal and urinary disorders
Proteinuria	14/109 (12.8%)
Respiratory, thoracic and mediastinal disorders
Cough	32/109 (29.4%)
Dyspnoea	29/109 (26.6%)
Epistaxis	27/109 (24.8%)
Oropharyngeal Pain	14/109 (12.8%)
Dysphonia	10/109 (9.2%)
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome	71/109 (65.1%)
Alopecia	32/109 (29.4%)
Rash	21/109 (19.3%)
Nail Disorder	13/109 (11.9%)
Pruritus	12/109 (11%)
Erythema	10/109 (9.2%)
Dry Skin	9/109 (8.3%)
Skin Reaction	9/109 (8.3%)
Vascular disorders
Hypertension	29/109 (26.6%)
Hot Flush	6/109 (5.5%)

Limitations/Caveats

The primary endpoint TTP was changed to overall survival (OS) due to issues regarding tumor assessment data based on RECIST and poor response from investigators to related queries that developed after the planned interim analysis.

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.