Paclitaxel With / Without GW572016 (Lapatinib) As First Line Therapy For Women With Advanced Or Metastatic Breast Cancer

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00075270

First received: January 7, 2004

Last updated: April 16, 2015

Last verified: February 2014

History of Changes

Results First Received: March 14, 2013

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Neoplasms, Breast
Interventions:	Drug: Paclitaxel Drug: GW572016 (Lapatinib)

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 580 participants were enrolled and randomized to treatment; however one participant withdrew from the study before taking any medication. Thus, only 579 participants were included in the Intent-to-Treat Population (comprised of all randomized participants who had received at least one dose of randomized therapy [lapatinib or placebo]).

Reporting Groups

	Description
Lapatinib With Paclitaxel	Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.

Participant Flow: Overall Study

	Lapatinib With Paclitaxel	Placebo With Paclitaxel
STARTED	291	288
Missing	26 ^[1]	13 ^[1]
COMPLETED	5	4
NOT COMPLETED	286	284
Withdrawal by Subject	28	21
Lost to Follow-up	25	28
Protocol Violation	0	2
Death	198	215
Other/Unknown	9	5
Missing	26	13

[1]	These participants have no completion status information recorded on the case report forms.

Baseline Characteristics

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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.
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Reporting Groups

	Description
Lapatinib With Paclitaxel	Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Total	Total of all reporting groups

Baseline Measures

	Lapatinib With Paclitaxel	Placebo With Paclitaxel	Total
Number of Participants [units: participants]	291	288	579
Age [units: Years] Mean (Standard Deviation)	51.3 (10.45)	52.4 (10.98)	51.8 (10.72)
Gender [units: Participants]
Female	291	288	579
Male	0	0	0
Race/Ethnicity, Customized [units: participants]
White	190	182	372
Black	10	10	20
Asian	30	35	65
American Hispanic	54	53	107
Unknown	7	8	15

Outcome Measures

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1. Primary:

Time to Progression as Evaluated by the Investigator [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

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2. Primary:

Time to Progression as Evaluated by the Independent Review Committee (IRC) [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

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3. Secondary:

Number of Participants With Tumor Response as Evaluated by the Investigator [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

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4. Secondary:

Number of Participants With Tumor Response as Evaluated by the Independent Review Committee [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

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5. Secondary:

Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

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6. Secondary:

Number of Participants With a Response of CR or PR by the Indicated Study Week [ Time Frame: Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72 ]

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7. Secondary:

Duration of Response (DOR) [ Time Frame: From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks) ]

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8. Secondary:

Progression-Free Survival (PFS) [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

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9. Secondary:

Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS) [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

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10. Secondary:

Overall Survival [ Time Frame: Randomization until the date of death due to any cause (average of 24 months) ]

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11. Secondary:

Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

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12. Secondary:

Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

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13. Secondary:

Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

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Measure Type	Secondary
Measure Title	Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores
Measure Description	The TOI questionnaire was designed to measure multidimensional QOL in participants with cancer and includes subscales for physical, functional well-being, and additional cancer concerns. The physical and functional well-being subscale scores range from 0 to 28, based on 7 questions (each question scored from 0 [not at all] to 4 [very much]); the breast cancer unweighted subscale scores range from 0 to 36, based on 9 questions. The total TOI score (ranging from 0 [better QOL] to 92 [worse QOL]) is the sum of the TOI subscale scores.
Time Frame	Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal
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.
ITT Population. Only participants contributing data at the indicated time points were analyzed. Only observed data were collected, and score analyses were conducted using the LOCF method.

Reporting Groups

	Description
Lapatinib With Paclitaxel	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.

Measured Values

	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Number of Participants Analyzed [units: participants]	208	232
Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores [units: Scores on a scale] Mean (Standard Deviation)
Week 9, n=208, 232	-2.3 (12.32)	-2.6 (11.88)
Week 21, n=126, 125	-0.5 (11.99)	-2.7 (12.42)
Week 33, n=72, 65	-0.1 (12.83)	-2.9 (9.05)
Week 45, n=36, 38	1.5 (15.91)	-2.8 (8.98)
Withdrawal, n=190, 212	-4.4 (14.30)	-6.1 (12.84)

No statistical analysis provided for Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores

14. Secondary:

Number of Participants With the Indicated ErbB2 Status at Baseline [ Time Frame: Baseline ]

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15. Secondary:

ErbB2 Ratio [ Time Frame: Baseline ]

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16. Secondary:

Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening [ Time Frame: Screening (Day -1) ]

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17. Secondary:

Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results [ Time Frame: Baseline ]

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18. Secondary:

Serum ErbB1 Concentration [ Time Frame: Screening (Day-1) and Withdrawal (up to Study Week 129) ]

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19. Secondary:

Serum ErbB2 Concentration [ Time Frame: Screening (Day-1) and Withdrawal (up to Study Week 129) ]

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20. Secondary:

Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4 [ Time Frame: Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks) ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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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
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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.

Results Point of Contact:

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

Publications:

Tenori L, Oakman C, Claudino WM, Bernini P, Cappadona S, Nepi S, Biganzoli L, Arbushites MC, Luchinat C, Bertini I, Di Leo A. Exploration of serum metabolomic profiles and outcomes in women with metastatic breast cancer: a pilot study. Mol Oncol. 2012 Aug;6(4):437-44. doi: 10.1016/j.molonc.2012.05.003. Epub 2012 Jun 1.

Finn RS, Press MF, Dering J, Arbushites M, Koehler M, Oliva C, Williams LS, Di Leo A. Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor expression and benefit from lapatinib in a randomized trial of paclitaxel with lapatinib or placebo as first-line treatment in HER2-negative or unknown metastatic breast cancer. J Clin Oncol. 2009 Aug 20;27(24):3908-15. doi: 10.1200/JCO.2008.18.1925. Epub 2009 Jul 20.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sherrill B, Di Leo A, Amonkar MM, Wu Y, Zvirbule Z, Aziz Z, Bines J, Gomez HL. Quality-of-life and quality-adjusted survival (Q-TWiST) in patients receiving lapatinib in combination with paclitaxel as first-line treatment for metastatic breast cancer. Curr Med Res Opin. 2010 Apr;26(4):767-75. doi: 10.1185/03007991003590860.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00075270 History of Changes
Obsolete Identifiers:	NCT00085046
Other Study ID Numbers:	EGF30001
Study First Received:	January 7, 2004
Results First Received:	March 14, 2013
Last Updated:	April 16, 2015
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices United States: Food and Drug Administration

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