Lapatinib In Combination With Chemotherapy In Subjects With Relapsed Breast Cancer

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00479856
• Collaborator: (none)
• Enrollment: 9
• Locations: 28
• Arm: 1
• Duration (Months): 28
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of lapatinib in combination with chemotherapy (capecitabine, docetaxel, nab-paclitaxel) in subjects with ErbB2-overexpressing breast cancer whose disease has progressed during or within 12 months after completion of trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.

Condition or Disease	Intervention/Treatment	Phase
Relapsed Breast Cancer; Neoplasms, Breast	Drug: Lapatinib; Drug: Capecitabine; Drug: Docetaxel; Drug: nab-Paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multi-centre Study of Lapatinib in Combinationwith Chemotherapy in Patients With ErbB2 Overexpressing Breastcancer After Trastuzumab Failure in the Neoadjuvant or Adjuvantsetting.
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lapatinib plus Chemotherapy Lapatinib is administered in combination with one of the following chemotherapies based on the discretion of the investigator : capecitabine, docetaxel or nab-paclitaxel.	Drug: Lapatinib; Small molecule tyrosine kinase inhibitor; Drug: Capecitabine; Chemotherapy; Drug: Docetaxel; Chemotherapy; Drug: nab-Paclitaxel; Chemotherapy

Outcome Measures

Primary Outcome Measures

1. Overall Tumor Response [from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 wks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, of other reason)]

   Overall tumor response is defined as the percentage of participants with a confirmed complete or partial tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is defined as the disappearance of all target lesions. CR could only be declared if all target and non-target lesions had disappeared. Partial response (PR) is defined as a decrease of 30% or greater in the sum of the longest diameter of target lesions.

Secondary Outcome Measures

1. Clinical Benefit (CB) [from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason)]

   CB is defined as the percentage of participants (par.) with either a confirmed CR or PR or stable disease (SD) for at least 24 weeks. SD is defined as small changes that do not meet criteria for CR, PR, or Progressive Disease (defined as at least a 20% increase in the sum of the longest diameter of target lesions).

2. Duration of Response [time from first documented evidence of CR or PR until the first documented sign of disease progression or death (approximately 95 weeks)]

   For the subset of participants with a confirmed CR or PR, duration of response was measured as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

3. Time to Response (TTR) [start of treatment until first documented evidence of CR or PR (approximately 95 weeks)]

   TTR is defined as the time from the start of treatment until the first documented evidence of PR or CR (whichever status was recorded first). When tumor response was confirmed at a repeat assessment, the TTR was taken to be the first time that the response was observed.

4. Progression-free Survival [from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks); dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason)]

   The time from the start of treatment until the earliest date of disease progression or death due to any cause was measured.

5. Number of Participants With the Indicated Serious Adverse Events and Adverse Events [Baseline through End of Treatment, or discontinuation of study therapy (approximately 95 weeks); from the first dose of lapatinib until 5 days after the last dose of lapatinib]

   Qualitative and quantitative toxicities associated with the combination of capecitabine, docetaxel, or nab-paclitaxel and lapatinib were measured. Data are presented as serious adverse events (SAEs) and adverse events (AEs). See the SAE/AE section of the results record for data.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Signed informed consent.

• Histologically/cytologically confirmed breast cancer;

If the disease is restricted to a solitary lesion, the neoplastic nature of the lesion must be confirmed by cytology or histology.

• Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors) [Therasse, 2000].

• Documented amplification of the ErbB2 gene by fluorescence in situ hybridization (FISH) or documented overexpression of the ErbB2 protein by 3+ IHC in primary or metastatic tumor tissue.

• Subjects must have relapsed breast cancer where the disease progressed during or ≤ 12 months after completion of trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.

Note: Progression is defined using RECIST criteria, that is, either the appearance of new lesions or a >=20% increase in the sum of longest diameter (LD).

• Subjects must not have received prior anti-cancer therapy for metastatic breast cancer (MBC). Subjects who received prior antihormonal agents combined with trastuzumab for the treatment of disease which first presented as ER positive MBC and recurred while receiving trastuzumab or ≤ 3 months after completing this therapy are eligible.

• Subjects with stable central nervous system (CNS) metastases as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI) are allowed. Treatment with prophylactic anticonvulsants is permitted, unless listed within the Prohibited Medications.

• Subjects must have a baseline cardiac ejection fraction (LVEF) ³50% measured by echocardiogram (ECHO) (or multigated acquisition (MUGA) scan if an ECHO cannot be performed). The same modality used at baseline must be used for repeat assessment throughout study. Only subjects with controlled or asymptomatic angina or arrhythmias are eligible.

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.

• Subjects must have archived tumor tissue from the initial diagnosis available for analysis. If tissue from the initial diagnosis is not available, then tissue must be obtained from a recurrent or metastatic site prior to initiating study treatment.

• Female ≥18 years.

• Subject must have adequate organ function as defined in Table 1.

• Table 1: Baseline Laboratory Values for Adequate Organ Function.

SYSTEM

Hematologic:

Absolute neutrophil count: ≥1.5 X 10^9/L

Hemoglobin: ≥9 g/dL

Platelets: ≥ 75 X 10^9/L

Hepatic:

AST, ALT and Alkaline phosphatase: ≤ 2.5 X ULN

Unless concomitant docetaxel, then ≤ 1.5 x ULN for AST and ALT, with AP ≤ 2.5 x ULN

Unless documented liver metastasis, then ≤ 5 x ULN

Serum bilirubin: ≤ 2.0 X ULN

Albumin: ≥ 2.5 g/dL

Renal:

Serum Creatinine: ≤ 1.5 mg/dL

• OR - Calculate Creatinine Clearance: ≥ 40 mL/min

1. Calculated by the Cockcroft and Gault Method [Cockcroft , 1976].

Exclusion Criteria:

• Pregnant or lactating females.

• Women of childbearing potential who do not practice approved contraceptive methods (for example, intrauterine device [IUD], birth control pills, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product.

• History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

• Concurrent therapy given to treat cancer (chemotherapy, radiation therapy, immunotherapy, biologic therapy, anti-hormonal therapy) while taking study medication.

• Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.

• Malabsorption syndrome or resection of the stomach or small bowel significantly affecting gastrointestinal function.

• Have current active haptic or biliary disease (with excpetion of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).

• Concurrent disease or condition that, in the opinion of the physician, would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety (for example, uncontrolled infection, or any psychiatric condition prohibiting understanding or rendering of informed consent).

• Concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents for anti-cancer therapy.

• Bisphosphonates may not be initiated after the first dose of study medication.

• Considered by the Investigator to have a life expectancy less than 3 months.

• Not able to swallow or retain oral medication.

• The subject with a known unmanageable hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients and those related to capecitabine, docetaxel, nab paclitaxel or their excipients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Hot Springs	Arkansas	United States	71913
2	GSK Investigational Site	Anaheim	California	United States	92801
3	GSK Investigational Site	Burbank	California	United States	91505
4	GSK Investigational Site	Highland	California	United States	92346
5	GSK Investigational Site	Long Beach	California	United States	90806
6	GSK Investigational Site	Sacramento	California	United States	95819
7	GSK Investigational Site	Washington	District of Columbia	United States	20007
8	GSK Investigational Site	Fort Lauderdale	Florida	United States	33328
9	GSK Investigational Site	Hollywood	Florida	United States	33021
10	GSK Investigational Site	Orlando	Florida	United States	32806
11	GSK Investigational Site	Atlanta	Georgia	United States	30341
12	GSK Investigational Site	Lawrenceville	Georgia	United States	30045
13	GSK Investigational Site	Zion	Illinois	United States	60099
14	GSK Investigational Site	Indianapolis	Indiana	United States	46227
15	GSK Investigational Site	Metairie	Louisiana	United States	70006
16	GSK Investigational Site	New Orleans	Louisiana	United States	70112
17	GSK Investigational Site	Baltimore	Maryland	United States	21237
18	GSK Investigational Site	Minneapolis	Minnesota	United States	55426
19	GSK Investigational Site	Tupelo	Mississippi	United States	38801
20	GSK Investigational Site	Voorhees	New Jersey	United States	08043
21	GSK Investigational Site	Albuquerque	New Mexico	United States	87131-0001
22	GSK Investigational Site	New York	New York	United States	10016
23	GSK Investigational Site	Sumter	South Carolina	United States	29150
24	GSK Investigational Site	Austin	Texas	United States	78705
25	GSK Investigational Site	San Antonio	Texas	United States	78229
26	GSK Investigational Site	Ogden	Utah	United States	84403
27	GSK Investigational Site	Abingdon	Virginia	United States	24211
28	GSK Investigational Site	Fairfax	Virginia	United States	22031

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00479856
• Other Study ID Numbers: EGF108916
• First Posted: May 28, 2007
• Last Update Posted: Jun 5, 2012
• Last Verified: Jun 1, 2011

• Keywords provided by GlaxoSmithKline: ErbB1; ErbB2; GW572016; lapatinib; Relapsed breast cancer; dual tyrosine kinase inhibitor; MBC; EGFR; Her-2/neu; FISH amplification
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Docetaxel; Capecitabine; Lapatinib

Study Results

Participant Flow

Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Period Title: Overall Study
STARTED	9
COMPLETED	6
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.9 (12.3)
Sex: Female, Male (Count of Participants)
Female	9 100%
Male	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	7 77.8%
African American/African Heritage	1 11.1%
American Indian or Alaska Native	1 11.1%

Outcome Measures

1. Primary Outcome

Title	Overall Tumor Response
Description	Overall tumor response is defined as the percentage of participants with a confirmed complete or partial tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is defined as the disappearance of all target lesions. CR could only be declared if all target and non-target lesions had disappeared. Partial response (PR) is defined as a decrease of 30% or greater in the sum of the longest diameter of target lesions.
Time Frame	from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 wks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, of other reason)

Outcome Measure Data

Analysis Population Description

All Treated Subjects (ATS) Population: all participants who received at least one dose of study treatment

Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Measure Participants	9
Number [percentage of participants]	33.3 370%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lapatinib + Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	33.3
	Confidence Interval	() 95%; 7.5 to 70.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Clinical Benefit (CB)
Description	CB is defined as the percentage of participants (par.) with either a confirmed CR or PR or stable disease (SD) for at least 24 weeks. SD is defined as small changes that do not meet criteria for CR, PR, or Progressive Disease (defined as at least a 20% increase in the sum of the longest diameter of target lesions).
Time Frame	from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason)

Outcome Measure Data

Analysis Population Description

Due to the low incidence of relapse and hence the difficulty in identifying eligible par., the study was terminated with only 9 out of the 45 planned par. enrolled. As there were too few par. to derive statistically meaningful conclusions, only the primary endpoint was evaluated.

Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Measure Participants	0

3. Secondary Outcome

Title	Duration of Response
Description	For the subset of participants with a confirmed CR or PR, duration of response was measured as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.
Time Frame	time from first documented evidence of CR or PR until the first documented sign of disease progression or death (approximately 95 weeks)

Outcome Measure Data

Analysis Population Description

Due to the low incidence of relapse and hence the difficulty in identifying eligible participants, the study was terminated with only 9 out of the 45 planned participants enrolled. As there were too few participants to derive statistically meaningful conclusions, only the primary endpoint was evaluated.

Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Measure Participants	0

4. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR is defined as the time from the start of treatment until the first documented evidence of PR or CR (whichever status was recorded first). When tumor response was confirmed at a repeat assessment, the TTR was taken to be the first time that the response was observed.
Time Frame	start of treatment until first documented evidence of CR or PR (approximately 95 weeks)

Outcome Measure Data

Analysis Population Description

Due to the low incidence of relapse and hence the difficulty in identifying eligible participants, the study was terminated with only 9 out of the 45 planned participants enrolled. As there were too few participants to derive statistically meaningful conclusions, only the primary endpoint was evaluated.

Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Measure Participants	0

5. Secondary Outcome

Title	Progression-free Survival
Description	The time from the start of treatment until the earliest date of disease progression or death due to any cause was measured.
Time Frame	from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks); dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason)

Outcome Measure Data

Analysis Population Description

Due to the low incidence of relapse and hence the difficulty in identifying eligible participants, the study was terminated with only 9 out of the 45 planned participants enrolled. As there were too few participants to derive statistically meaningful conclusions, only the primary endpoint of overall response rate was evaluated.

Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Measure Participants	0

6. Secondary Outcome

Title	Number of Participants With the Indicated Serious Adverse Events and Adverse Events
Description	Qualitative and quantitative toxicities associated with the combination of capecitabine, docetaxel, or nab-paclitaxel and lapatinib were measured. Data are presented as serious adverse events (SAEs) and adverse events (AEs). See the SAE/AE section of the results record for data.
Time Frame	Baseline through End of Treatment, or discontinuation of study therapy (approximately 95 weeks); from the first dose of lapatinib until 5 days after the last dose of lapatinib

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
Measure Participants	0

Adverse Events

Time Frame	Time from the first dose of lapatinib until 5 days after the last dose of lapatinib.
Arm/Group Title	Lapatinib + Chemotherapy
Arm/Group Description	1250 milligrams (mg) Lapatinib taken once daily on a continuous basis plus one of the following chemotherapies: (1) 1000 mg/square meters (m2) Capecitabine taken twice a day on Days 1-14 every 21 days; (2) 75 mg/m2 Docetaxel administered as a single infusion once every 21 days; or (3) 100 mg/m2 nab-Paclitaxel administered as a single infusion once every 7 days for 21 days, followed by 7 days of rest in a 28-day cycle
All Cause Mortality
	Lapatinib + Chemotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lapatinib + Chemotherapy
	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)
Gastrointestinal disorders
Small intestinal obstruction	1/9 (11.1%)
Small intestinal perforation	1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Lapatinib + Chemotherapy
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Blood and lymphatic system disorders
Anaemia	3/9 (33.3%)
Leukopenia	1/9 (11.1%)
Lymphadenopathy	1/9 (11.1%)
Neutropenia	1/9 (11.1%)
Thrombocytopenia	1/9 (11.1%)
Eye disorders
Conjunctivitis	1/9 (11.1%)
Gastrointestinal disorders
Diarrhoea	7/9 (77.8%)
Nausea	6/9 (66.7%)
Vomiting	4/9 (44.4%)
Constipation	3/9 (33.3%)
Dyspesia	2/9 (22.2%)
Abdominal pain upper	1/9 (11.1%)
Haemorrhoids	1/9 (11.1%)
Rectal haemorrhage	1/9 (11.1%)
Small intestinal obstruction	1/9 (11.1%)
Small intestinal perforation	1/9 (11.1%)
General disorders
Fatigue	7/9 (77.8%)
Mucosal inflammation	2/9 (22.2%)
Chest pain	1/9 (11.1%)
Feeling cold	1/9 (11.1%)
Local swelling	1/9 (11.1%)
Pain	1/9 (11.1%)
Infections and infestations
Urinary tract infection	2/9 (22.2%)
Paronychia	1/9 (11.1%)
Periorbital cellulitis	1/9 (11.1%)
Upper respiratory tract infection	1/9 (11.1%)
Vulvovaginal mycotic infection	1/9 (11.1%)
Investigations
Aspartatate aminotransferase increased	2/9 (22.2%)
Alanine aminotransferase increased	1/9 (11.1%)
Weight decreased	1/9 (11.1%)
Metabolism and nutrition disorders
Hypokalaemia	3/9 (33.3%)
Hypocalcaemia	2/9 (22.2%)
Hyperlipidaemia	1/9 (11.1%)
Hypoalbuminaemia	1/9 (11.1%)
Hypoglycaemia	1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Pain in extremity	2/9 (22.2%)
Back pain	1/9 (11.1%)
Musculoskeletal pain	1/9 (11.1%)
Nervous system disorders
Headache	2/9 (22.2%)
Dysgeusia	1/9 (11.1%)
Neuropathy peripheral	1/9 (11.1%)
Psychiatric disorders
Insomnia	1/9 (11.1%)
Renal and urinary disorders
Proteinuria	1/9 (11.1%)
Reproductive system and breast disorders
Menorrhagia	1/9 (11.1%)
Vulvovaginal dryness	1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	1/9 (11.1%)
Dyspnoea	1/9 (11.1%)
Skin and subcutaneous tissue disorders
Palmar plantar erythrodysaesthesia	5/9 (55.6%)
Rash	4/9 (44.4%)
Skin chapped	1/9 (11.1%)
Skin discolouration	1/9 (11.1%)
Skin exfoliation	1/9 (11.1%)
Skin hyperpigmentation	1/9 (11.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.