Clinical Trial Results:
An open-label, single-arm, multicentre, Phase II study of oral lapatinib in combination with paclitaxel as first-line treatment for ErbB2-amplified metastatic breast cancer patients
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Summary
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EudraCT number |
2005-003945-16 |
Trial protocol |
LV |
Global end of trial date |
20 Nov 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
07 Feb 2016
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First version publication date |
26 Mar 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EGF105764
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Apr 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Nov 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate overall tumour response rate (ORR) of lapatinib combined with paclitaxel in patients with ErbB2-amplified metastatic breast cancer
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Protection of trial subjects |
Not Applicable
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
13 May 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Latvia: 5
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Country: Number of subjects enrolled |
Poland: 15
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Country: Number of subjects enrolled |
Russian Federation: 33
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Country: Number of subjects enrolled |
Romania: 4
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Worldwide total number of subjects |
57
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EEA total number of subjects |
24
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
50
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Study medication was dispensed to the subject on Day 1 after it was confirmed that the participants met all eligibility criteria and all screening assessments were completed. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Lapatinib with paclitaxel | ||||||||||||||||||||
Arm description |
Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel, administered as a 1-hour intravenous (IV) infusion at a dose of 80 mg/meters squared (m^2) on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Lapatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1500mg, orally, OD
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
80mg/m2 ,IV weekly for 3 weeks in a 4 week cycle
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Baseline characteristics reporting groups
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Reporting group title |
Lapatinib with paclitaxel
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Reporting group description |
Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel, administered as a 1-hour intravenous (IV) infusion at a dose of 80 mg/meters squared (m^2) on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lapatinib with paclitaxel
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Reporting group description |
Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel, administered as a 1-hour intravenous (IV) infusion at a dose of 80 mg/meters squared (m^2) on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal. | ||
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End point title |
Number of participants (par) with a best overall response (OR) of confirmed complete response (CR) or partial response (PR), as assessed by the Independent Review Committee (IRC) [1] | ||||||||||
End point description |
OR is defined as the number of par achieving either a CR or PR. The best OR is the best response recorded from the start of treatment(trt) until progressive disease(PD)/recurrence. CR is the disappearance of all target lesions (TLs) and non-TLs. PR is at least a 30% decrease in the sum of the longest diameters(LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the trt started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Par with an unknown or missing response are treated as non-responders. The estimated value(EV) represents the % of par with a confirmed CR or PR. Confidence interval 95% (37.3, 64.4); EV 50.9.
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End point type |
Primary
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End point timeframe |
From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The system does not allow for statistical analysis for studies with a single treatment arm. Statistical comparison between category results are provided in the endpoint description. |
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| Notes [2] - Intent-to-Treat (ITT) Population: all participants who received study medication. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of participants with a best overall response (OR) of confirmed complete response (CR) or partial response (PR), as assessed by the Investigator | ||||||||||
End point description |
OR is defined as the number of participants achieving either a CR or PR, per RECIST. The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the Investigator. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.
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End point type |
Secondary
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End point timeframe |
From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)
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| Notes [3] - ITT Population |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Duration of response (DoR), as assessed by the IRC | ||||||||
End point description |
DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL[s]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as a >=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.
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End point type |
Secondary
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End point timeframe |
From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)
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| Notes [4] - ITT Population. Only those participants with CR or PR were analyzed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of response (DoR), as assessed by the Investigator | ||||||||
End point description |
DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL[s]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as a >=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.
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End point type |
Secondary
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End point timeframe |
From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)
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| Notes [5] - ITT Population. Only those participants with CR or PR were analyzed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to response, as assessed by the IRC | ||||||||
End point description |
Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.
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End point type |
Secondary
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End point timeframe |
From randomization until the first documented evidence of a PR or CR (up to Week 86)
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| Notes [6] - ITT Population. Only those participants with CR or PR were analyzed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to response, as assessed by the Investigator | ||||||||
End point description |
Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.
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End point type |
Secondary
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End point timeframe |
From randomization until the first documented evidence of a PR or CR (up to Week 86)
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| Notes [7] - ITT Population. Only those participants with CR or PR were analyzed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to progression, as assessed by the IRC and the Investigator | ||||||||||||
End point description |
Time to progression is defined as the interval between the start date of treatment and the date of radiological disease progression or death due to breast cancer, whichever occurs first. Participents who did not progress or die were censored on the date of their last radiological assessment preceding the start of any additional anti-cancer therapy. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at a subsequent assessment made no less than 28 days after the original response. Please note that the IRC upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate; therefore the value of 99999 was entered which represents NA.
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End point type |
Secondary
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End point timeframe |
From the start date of treatment until the date of radiological disease progression or the date of death due to breast cancer (up to Week 86)
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| Notes [8] - ITT Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Progression-free survival, as assessed by the IRC and the Investigator | ||||||||||||
End point description |
Progression-free survival is defined as the interval between the start date of treatment and the date of radiological disease progression or death due to any cause, whichever occurs first. Participants who did not progress in their disease were censored on the date of their last radiological assessment preceding the start of any additional anti-cancer therapy. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at a subsequent assessment made no less than 28 days after the original response. Please note that the IRC upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate; therefore, the value of 99999 was entered which represents NA.
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End point type |
Secondary
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End point timeframe |
From the start date of treatment until the date of radiological disease progression or death due to any cause, whichever occurs first (up to Week 86)
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| Notes [9] - ITT Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall survival | ||||||||
End point description |
Overall survival is defined as the interval between the date of treatment start and the date of death due to any cause. For participants who did not die, follow-up was censored as the date of last contact. For participants who did not die, follow-up was censored at the date of last contact. At the time of this analysis, the median and the 95% confidence interval could not be determined because there were not enough deaths to calculate these estimates; therefore, the value of 99999 was entered which represents NA.
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End point type |
Secondary
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End point timeframe |
From the date of the first dose until the date of death due to any cause (up to Week 86)
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| Notes [10] - ITT Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of participants with any adverse event (AE) or serious adverse event (SAE) | ||||||||||
End point description |
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations.
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End point type |
Secondary
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End point timeframe |
From the start of study medication until 28 days after the last dose (up to Study Week 381)
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| Notes [11] - ITT Population |
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381).
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Adverse event reporting additional description |
SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Lapatinib plus paclitaxel
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Reporting group description |
Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Apr 2007 |
Amendment 1/ to allow use of generic paclitaxel |
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13 Jun 2008 |
Amendment 2/ The protocol has been amended to include the information regarding hepatotoxicity associated
with lapatinib treatment. |
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14 Jul 2008 |
Amendment 2/ As part of the liver toxicity update of GM2005/00370/02, inclusion of pharmacokinetics sample needing to be taken has been added to the follow up criteria in section 6.2.3.2. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
