Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00281658

First received: January 23, 2006

Last updated: January 24, 2013

Last verified: January 2013

History of Changes

Results First Received: May 5, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Conditions:	Her2+ Metastatic Breast Cancer Neoplasms, Breast Cancer ErbB2+
Interventions:	Drug: lapatinib (GW572016) oral tablets Drug: paclitaxel infusion

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
At the time of disease progression, participants had the option to be unblinded. Participants (pts) who were on placebo+paclitaxel could continue in an open-label lapatinib monotherapy extension phase until further progression or an unacceptable toxicity. All participants were followed for survival. The unblinding was performed by a third party.

Reporting Groups

	Description
Lapatinib Plus Paclitaxel	Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks
Placebo Plus Paclitaxel	Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks
Lapatinib 1500 mg	Lapatinib 1500 mg administered once daily

Participant Flow for 2 periods

Period 1: Double-blind, Randomized Phase

	Lapatinib Plus Paclitaxel	Placebo Plus Paclitaxel
STARTED	222	222 ^[1]
COMPLETED	85 ^[2]	168 ^[2]
NOT COMPLETED	137	54
Death	120	46
Lost to Follow-up	12	5
Withdrawal by Subject	4	1
Participant Entered New Protocol	1	1
Screen Failure; Randomized in Error	0	1

[1]	Of these participants, 149 entered the open-label extension phase.
[2]	For the purposes of this report, completed pts are pts ongoing at the time of the analysis.

Period 2: Open-label Monotherapy Extension Phase

	Lapatinib Plus Paclitaxel	Placebo Plus Paclitaxel	Lapatinib 1500 mg
STARTED	0	0	149
COMPLETED	0	0	48 ^[1]
NOT COMPLETED	0	0	101
Death	0	0	97
Lost to Follow-up	0	0	3
Withdrawal by Subject	0	0	1

[1]	For the purposes of this report, completed pts are pts ongoing at the time of the analysis.

Baseline Characteristics

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Reporting Groups

	Description
Lapatinib Plus Paclitaxel	Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks
Placebo Plus Paclitaxel	Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks
Total	Total of all reporting groups

Baseline Measures

	Lapatinib Plus Paclitaxel	Placebo Plus Paclitaxel	Total
Number of Participants [units: participants]	222	222	444
Age [units: Years] Mean ± Standard Deviation	49.1 ± 10.74	49.3 ± 9.75	49.2 ± 10.25
Gender [units: Participants]
Female	222	217	439
Male	0	5	5
Race/Ethnicity, Customized [units: participants]
White	9	13	22
Asian	192	192	384
Hispanic	21	16	37
Missing	0	1	1
Number of participants with any visceral metastatic disease and with only non-visceral disease ^[1] [units: participants]
Visceral	187	186	373
Non-visceral	35	36	71
Number of Participants with the Indicated Hormone Receptor Status ^[2] [units: participants]
ER+ and/or PgR+ or Unknown	111	113	224
ER- and PgR-	111	109	220
Number of Participants with the Indicated Stage of Disease at Initial Diagnosis ^[3] [units: participants]
Stage I to II	107	119	226
Stage III	75	68	143
Stage IV	30	24	54
Unknown	10	11	21
Number of Participants with the Indicated Eastern Cooperative Oncology Group Performance Status ^[4] [units: participants]
0, Fully Active	103	113	216
1, Ambulatory, Restricted Strenuous Activity	119	109	228
Number of Participants with the Indicated Number of Metastatic Sites ^[5] [units: participants]
Greater than or equal to 3	131	115	246
Less than 3	91	107	198
Number of Participants in the Indicated Age Groups [units: participants]
Greater than or equal to 65 years of age	16	13	29
Less than 65 years of age	206	209	415
Mean Time of Disease-Free Interval ^[6] [units: months] Mean ± Standard Deviation	27.51 ± 27.481	29.04 ± 34.522	28.27 ± 31.174

[1]	Metastasis is defined as the spread of a tumor or cancerous cells from the primary site to one or more sites elsewhere in the body. Visceral metastasis is defined as the spread of cancer to viscera, the internal organs of the body, specifically those within the chest (as the heart or lungs) or abdomen (as the liver, pancreas, or intestines). Non-visceral organs are defined as any organ not considered visceral.
[2]	Cancer cells have hormone receptor expression of Estrogen Receptor (ER) and/or Progesterone Receptor (PR) and are thus considered to be ER+ and/or PgR+ cells, respectively.
[3]	The stage of cancer is a description of the extent to which the cancer has spread. Stage I cancer is localized; Stage II cancer has not started to spread into the surrounding tissue, but the tumor is larger than in Stage I; Stage III cancer is locally advanced and/or involves local lymph nodes; Stage IV cancer has spread to other organs.
[4]	Eastern Cooperative Oncology Group (ECOG) Performance Status classifies participants according to their functional impairment, and scores indicate: 0, fully active; 1, ambulatory, restricted strenuous activity; 2, ambulatory, no work activity; 3, partially confined to bed; 5, death. Participants were required to have a baseline ECOG performance status of 0 or 1 for study participation.
[5]	Tumor cells move from the primary site to other sites in the body, where they continue to multiply and eventually form another clinically detectable tumor; thus, the site becomes metastatic.
[6]	The disease-free interval was defined as the time from initial diagnosis to metastases.

Outcome Measures

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1. Primary:

Overall Survival [ Time Frame: Randomization to death (up to maximum of Month 53) ]

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Measure Type	Primary
Measure Title	Overall Survival
Measure Description	Overall survival is defined as the time from randomization until death due to any cause.
Time Frame	Randomization to death (up to maximum of Month 53)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants

Reporting Groups

	Description
Lapatinib Plus Paclitaxel	Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks
Placebo Plus Paclitaxel	Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks

Measured Values

	Lapatinib Plus Paclitaxel	Placebo Plus Paclitaxel
Number of Participants Analyzed [units: participants]	222	222
Overall Survival [units: months] Median ( 95% Confidence Interval )	27.8 ( 23.2 to 32.2 )	20.5 ( 17.9 to 24.3 )

Statistical Analysis 1 for Overall Survival

Groups ^[1]	All groups
Method ^[2]	Wald Chi-squared
P Value ^[3]	0.0005
Hazard Ratio (HR) ^[4]	0.64
95% Confidence Interval	( 0.49 to 0.82 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted for hormonal status, metastatic disease site, initial diagnosis stage, ECOG status, number of metastatic sites, age and disease-free interval
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided p-value
[4]	Other relevant estimation information:
	Adjusted HR based on Cox Regression model

Statistical Analysis 2 for Overall Survival

Groups ^[1]	All groups
Method ^[2]	Log Rank
P Value ^[3]	0.0124
Hazard Ratio (HR) ^[4]	0.74
95% Confidence Interval	( 0.58 to 0.94 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Stratified log-rank test, stratifying for metastatic disease sites and hormonal status
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided p-value
[4]	Other relevant estimation information:
	No text entered.

2. Secondary:

Progression-free Survival [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]

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3. Secondary:

Overall Response (OR) [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]

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4. Secondary:

Clinical Benefit [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]

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5. Secondary:

Duration of Response [ Time Frame: Randomization to disease progression or death (up to a maximum of Month 53) ]

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6. Secondary:

Number of Participants With a CR or PR at Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 [ Time Frame: Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Some participants (PAR) are captured as withdrawing from the study due to death. Per protocol, PAR who died were considered to be study completers and did not withdraw from the study; for the purposes of this report, they are classified as withdrawn.

Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00281658 History of Changes
Other Study ID Numbers:	EGF104535
Study First Received:	January 23, 2006
Results First Received:	May 5, 2011
Last Updated:	January 24, 2013
Health Authority:	Ukraine: Central Ethics Committee; Brazil: Institutional Review Board Peru: Institutional Review Board Norway: Statens Legemiddelverk Russia: Russian Ministry of Health Thailand: Ministry of Public Health Hong Kong: Department of Health China: Food and Drug Administration United States: Food and Drug Administration

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