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Trial record 23 of 125 for:    lapatinib | Recruiting, Active, not recruiting, Completed Studies | Phase 2

Lapatinib Versus Placebo Given Concurrently With Cisplatin And Radiotherapy In Patients With Unresected Head And Neck Cancer

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ClinicalTrials.gov Identifier: NCT00387127
Recruitment Status : Completed
First Posted : October 12, 2006
Results First Posted : January 5, 2015
Last Update Posted : June 25, 2015
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Neoplasms, Head and Neck
Interventions Drug: Lapatinib oral tablets
Drug: radiotherapy
Drug: cisplatin chemotherapy
Enrollment 67
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal. Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Period Title: Overall Study
Started 33 34
Completed 0 0
Not Completed 33 34
Reason Not Completed
Lost to Follow-up             0             4
Death             16             16
Physician Decision             0             1
Withdrawal by Subject             3             2
Required by Protocol Amendment #4             12             10
Serious Adverse Event             1             1
Sponsor Unblinded             1             0
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib Total
Hide Arm/Group Description Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal. Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal. Total of all reporting groups
Overall Number of Baseline Participants 33 34 67
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 34 participants 67 participants
56.5  (6.61) 55.8  (5.73) 56.1  (6.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 67 participants
Female
2
   6.1%
5
  14.7%
7
  10.4%
Male
31
  93.9%
29
  85.3%
60
  89.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 67 participants
African American/African Heritage 0 1 1
American Indian or Alaska Native 2 2 4
Asian - Central/South Asian Heritage 3 6 9
Asian - South East Asian Heritage 2 1 3
White - White/Caucasian/European Heritage 26 24 50
1.Primary Outcome
Title Number of Participants (Par.) With Complete Response (CR), as Assessed by Independent Radiological Review
Hide Description Participants with CR are defined as those who achieved a complete tumor response at 6 months after the completion of the chemoradiation treatment (CRT), as assessed by independent radiological review. Tumor response was assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Per RECIST, CR is defined as the disappearance of all target and non-target lesions. Data are based on Week 24 scans from participants receiving study treatment at that time and on those in follow-up.
Time Frame From the date of randomization until 6 months post chemoradiation treatment, assessed for a median time of 13 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who were randomized to study treatment, regardless of whether they actually received study medication
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction &lt;2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Participants
12 18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemoradiotherapy + Placebo, Followed by Placebo, Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3658
Comments From exact test that common odds ratio equals 1
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage of par. with CR
Estimated Value 10.7
Confidence Interval (2-Sided) 95%
-13.4 to 37.3
Estimation Comments Complete response was defined as the percentage of participants achieving a CR as determined by an independent radiological review.
2.Secondary Outcome
Title Number of Participants With CR, as Assessed by the Investigator
Hide Description Participants with CR are defined as those who achieved a complete tumor response at 6 months after the completion of the CRT, as determined by the investigator. Tumor response was assessed using modified RECIST criteria. Per RECIST, CR is defined as the disappearance of all target and non-target lesions. Data are based on Week 24 scans from participants receiving study treatment at that time and on those in follow-up.
Time Frame From the date of randomization until 6 months post chemoradiation treatment, assessed after a median time of 13 months of follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Participants
7 17
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemoradiotherapy + Placebo, Followed by Placebo, Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0130
Comments From exact test that common odds ratio equals 1
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage of par. with CR
Estimated Value 28.8
Confidence Interval (2-Sided) 95%
5.7 to 53.6
Estimation Comments Complete response was defined as the percentage of participants achieving a CR as determined by the investigator.
3.Secondary Outcome
Title Progression-Free Survival (PFS), as Assessed by the Investigator
Hide Description PFS=the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. Per RECIST, progressive disease=a >=20% increase in the sum of the longest diameter of target lesions (TLs), or the appearance of >=1 new L, symptomatic progression and/or unequivocal progression of existing non-TLs. For participants who did not progress or die at the time of reporting (data cut-off 1-Aug-2014), PFS data were censored at the time of the last investigator assessed radiological scan preceding the initiation of any alternative anti-cancer therapy.
Time Frame From the date of randomization until the date of disease progression or death due to any cause, assessed after a median of 22 months of follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Median (95% Confidence Interval)
Unit of Measure: Months
12.1 [1] 
(7.3 to NA)
20.4 [1] 
(10.8 to NA)
[1]
There were too few events to allow for the calculation of the upper limit of the confidence interval.
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time from randomization until death due to any cause. Time to death (data cut-off 1-Aug-2014) was censored at the time of last contact for participants who did not die.
Time Frame From the date of randomization until the date of death due to any cause, assessed after a median of 30.9 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Median (95% Confidence Interval)
Unit of Measure: Months
23.0 [1] 
(14.2 to NA)
48.4 [1] 
(18.8 to NA)
[1]
There were too few events to allow for the calculation of the upper limit of the confidence interval.
5.Secondary Outcome
Title Number of Participants Who Died Due to Progressive Disease
Hide Description The number of participants who died due to progressive disease (a >=20% increase in the sum of the longest diameter of target lesions, or the appearance of >=1 new lesion, symptomatic progression and/or unequivocal progression of existing non-target lesions), or died due to head and neck cancer without evidence of disease progression, after randomization in the study is presented, using a data cut of 1 August 2014.
Time Frame From the date of randomization until the date of death due to disease under study, assessed after a median of 30.9 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Participants
11 8
6.Secondary Outcome
Title Disease-specific Survival
Hide Description Disease-specific survival is defined as the time from randomization until death due to head and neck cancer.
Time Frame From the date of randomization until the date of death due to disease, assessed after a median of 13 months of follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. For participants who did not die, time to death was censored at the time of last contact.
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Median (Inter-Quartile Range)
Unit of Measure: Months
NA [1] 
(15.6 to NA)
NA [2] 
(NA to NA)
[1]
The cumulative incidence in the placebo arm remained lower than 50%, so the median and upper quartile were not observed.
[2]
The cumulative incidence remained lower than 25% in the lapatinib arm, so neither the median nor the inter-quartile range were observed.
7.Secondary Outcome
Title Number of Participants With Loco-regional Recurrence of Initial Disease
Hide Description Participants with loco-regional recurrence were those who had progression of disease in the T and N sites. Per the Tumor, Node, and Metastases (TNM) staging of tumors: T describes the size of the tumor and whether it has invaded nearby tissue, and N describes regional lymph nodes that are involved. If a participant had progression in the T or N sites, then the participant was counted as having had an event of interest.
Time Frame From the date of randomization until progression in the T or N site or death due to any cause, assessed after a median of 30.9 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Participants
7 4
8.Secondary Outcome
Title Loco-regional Control
Hide Description Loco-regional control is defined as the time from the date of randomization until progression in the T or N site. Participants who died or had secondary primary malignancies in the head and neck region outside of the T and N site or distant metastasis were not counted as an event and were instead treated as competing risks. Per the TNM staging of tumors: T describes the size of the tumor and whether it has invaded nearby tissue, and N describes regional lymph nodes that are involved. Due to the minimal events reported (data cut-off 30-Sep-2010), valid analysis could not be performed for loco-regional control rate.
Time Frame From the date of randomization until progression in the T or N site or death due to any cause, assessed after a median of 30.9 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Number of Participants With Distant Recurrence of Initial Disease
Hide Description Participants were analyzed for the occurrence of distant metastasis (spread of a disease from one organ or part to another non-adjacent organ or part) after randomization in the study until data cut-off date 1-Aug-2014. Participants who died or had recurrence of disease in the T or N sites or secondary primary malignancies in the head and neck region outside of the original T and N site were not counted as an event and were instead treated as competing risks.
Time Frame From the date of randomization until the first occurrence of distant metastasis, assessed after a median of 30.9 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Participants
5 8
10.Secondary Outcome
Title Distant Relapse
Hide Description Distant relapse is defined as the time from the date of randomization until the first occurrence of distant metastasis (spread of a disease from one organ or part to another non-adjacent organ of part). Participants who died or had recurrence of disease in the T or N sites or secondary primary malignancies in the head and neck region outside of the original T and N site were not counted as an event and were instead treated as competing risks.
Time Frame From the date of randomization until the first occurrence of distant metastasis, assessed after a median of 30.9 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. If a participant had a distant metastasis and then died, then the participant was counted as having had an event of interest.
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Median (Inter-Quartile Range)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [2] 
(56.8 to NA)
[1]
The cumulative incidence remained below 25% in the placebo arm, so neither the median nor the inter-quartile range were observed.
[2]
The cumulative incidence in the lapatinib arm did not reach 50% (most participants had not relapsed), so the median and the upper limit of the interquartile range were not observed.
11.Secondary Outcome
Title Number of Participants With Overall Response (OR), as Assessed by the Investigator
Hide Description Participants with OR were those who achieved either a CR or partial response (PR) from the assessment of overall tumor response at 6 months (24 weeks) following completion of CRT (data cut-off 30-Sep-2010). Per RECIST, CR is defined as the disappearance of all target and non-target lesions; PR is defined as at least a 30% decrease in the sum of the long diameter (LD) of target lesions, taking as a reference, the baseline sum LD. Data are based on Week 24 scans from participants receiving study treatment at that time point.
Time Frame From the date of randomization until 6 months post chemoradiation treatment, assessed for a median of 13 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Participants
15 21
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemoradiotherapy + Placebo, Followed by Placebo, Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1969
Comments From exact test that common odds ratio equals 1
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in overall response rate
Estimated Value 16.3
Confidence Interval (2-Sided) 95%
-8.6 to 42.1
Estimation Comments Overall response was defined as the percentage of participants achieving a PR or CR as determined by the investigator.
12.Secondary Outcome
Title Number of Participants Positive and Negative for the Expression of Biomarkers in Tumor Tissue: Human Epidermal Growth Factor Receptor (HER)-1, HER2, HER3, HER4, P16, and Transforming Growth Factor (TGF-alpha)
Hide Description Paraffin-embedded tissue block (or sections) from archived tumor tissue sample, if available (from time of original diagnosis) or fresh tumor tissue, was sent for testing to determine intra-tumoral biomarker expression by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) assay. Stained tumor slides or tissue micro arrays (TMAs) were scored by a pathologist from 0 (no expression) to 3+ (high expression). An expression level of >=2+ was considered positive.
Time Frame Up to 28 days prior to the date of the first dose of lapatinib/placebo start
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Hide Analysis Population Description
ITT Population. Only those participants who had sufficient tumor sample for testing were analyzed.
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 30 27
Measure Type: Number
Unit of Measure: Participants
HER1, Positive, n=27, 24 27 19
HER1, Negative, n=27, 24 0 5
HER2, Positive, n=26, 25 3 0
HER2, Negative, n=26, 25 23 24
HER2, Missing, n=26, 25 0 1
HER3, Positive, n=27, 22 8 5
HER3, Negative, n=27, 22 18 16
HER3, Missing, n=27, 22 1 1
HER4, Positive, n=26, 25 0 0
HER4, Negative, n=26, 25 26 24
HER4, Missing, n=26, 25 0 1
P16 Positive, n=23, 23 3 4
P16, Negative, n=23, 23 20 19
TGF-alpha, Positive, n=24, 25 7 4
TGF-alpha, Negative, n=24, 25 17 20
TGF-alpha, Missing, n=24, 25 0 1
13.Secondary Outcome
Title Plasma Proteome Analysis
Hide Description Proteomic analyses of blood plasma samples were to be conducted to identify any changes in the proteome profile that could be related to the treatment response. Examination of pre-dosing (screening) plasma protein profiles could uncover novel blood-borne protein candidate biomarkers/profiles, which could be used to predict drug response.
Time Frame From up to 28 days prior to the first dose of lapatinib/placebo start to 8 weeks after the first dose
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Hide Analysis Population Description
ITT Population. Plasma proteome data have not been analyzed (tested); thus, data are not available to disclose. Based on the negative outcome of Study EGF102988 (NCT00424255), no suitable analyses have been proposed for this small sample size.
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Analysis of Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) From Tumor Samples
Hide Description No analysis was performed for tumor sample RNA/DNA.
Time Frame Screening
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Hide Analysis Population Description
ITT Population. DNA/RNA from tumors has not been analyzed (tested); therefore, data are not available. No suitable analyses of DNA/RNA have been proposed for this small sample size of tumor samples.
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Number of Participants Negative and Positive for Human Papilloma Virus (HPV) Infection, as Determined From Tumor Samples
Hide Description Analysis was performed for HPV infection analysis from the tumor biopsy samples obtained during the Screening period. p16 was used as a marker for HPV; thus, "negative" participants did not have the p16 marker.
Time Frame Up to 28 days prior to the first dose of lapatinib/placebo
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Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Participants
Negative 20 19
Positive 3 4
Unknown 10 11
16.Secondary Outcome
Title Number of Participants Positive and Negative for Biomarker HER1/ErbB1 Categorized in the Indicated Independent Review Panel-assessed Tumor Responses by Expression of Biomarkers From Tumor Tissue: Sensitivity Analysis - 0 Versus (1, 2, 3)
Hide Description Tumor tissue (fresh or archived) was sent to a central laboratory for biomarker HER1/ErbB1 and tumor genetics analysis up to 1 week after randomization. Per RECIST: CR, disappearance of all lesions; PR, a >=30% decrease in the sum of the longest dimensions (LD) of the target lesions (TLs) taking as a reference the baseline sum LD; Progressive disease (PD), a >=20% increase in the sum of the LD of TLs, or the appearance of >=1 new lesion; Stable Disease (SD), neither PR nor PD, persistence of >=1 non-TL. 0=negative; 1, 2, 3=positive (increasing level of biomarker expression).
Time Frame From the date of randomization until 6 months post chemoradiation treatment, assessed for up to 24 weeks
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Hide Analysis Population Description
ITT Population. Participants assessed for HER1/ ErbB1 expression were analyzed.
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 27 24
Measure Type: Number
Unit of Measure: Participants
Negative, CR 0 0
Negative, PR 0 0
Negative, SD 0 0
Negative, PD (Week 24) 0 0
Negative, PD or Death (prior to Week 24) 0 0
Negative, Not Evaluable 0 0
Negative, Unknown 0 0
Positive, CR 9 14
Positive, PR 4 3
Positive, SD 0 0
Positive, PD (Week 24) 4 1
Positive, PD or Death (prior to Week 24) 5 4
Positive, Not Evaluable 1 0
Positive, Unknown 4 2
17.Secondary Outcome
Title Number of Participants Positive and Negative for Biomarker HER1/ErbB1 Categorized in the Indicated Independent Review Panel-assessed Tumor Responses by Expression of Biomarkers From Tumor Tissues: Sensitivity Analysis - 0, 1, 2 Versus 3
Hide Description Tumor tissue (fresh or archived) was sent to a central laboratory for biomarker HER1/ErbB1 and tumor genetics analysis up to 1 week after randomization. Per RECIST: CR, disappearance of all lesions; PR, a >=30% decrease in the sum of the longest dimensions (LD) of the target lesions (TLs) taking as a reference the baseline sum LD; Progressive disease (PD), a >=20% increase in the sum of the LD of TLs, or the appearance of >=1 new lesion; Stable Disease (SD), neither PR nor PD, persistence of >=1 non-TL. 0=negative; 1, 2, 3=positive (increasing level of biomarker expression).
Time Frame From the date of randomization until 6 months post chemoradiation treatment, assessed for up to 24 weeks
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Hide Analysis Population Description
ITT Population. Participants assessed for HER1/ ErbB1 expression were analyzed.
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description:
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Participants
Negative, CR 5 9
Negative, PR 2 2
Negative, SD 0 0
Negative, PD (Week 24) 1 0
Negative, PD or Death (prior to Week 24) 2 4
Negative, Not Evaluable 0 0
Negative, Unknown 1 1
Positive, CR 4 5
Positive, PR 2 1
Positive, SD 0 0
Positive, PD (Week 24) 3 1
Positive, PD or Death (prior to Week 24) 3 0
Positive, Not Evaluable 1 0
Positive, Unknown 3 1
18.Other Pre-specified Outcome
Title Number of Participants Classified as Responders, as Per Volumetric Tumor Response
Hide Description No analysis was not performed.
Time Frame From the date of randomization until 6 months post chemoradiation treatment, assessed for a median of 13 months
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Hide Analysis Population Description
ITT Population. A formal analysis of this outcome measure was never performed; thus data are not available and cannot be reported.
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
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Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal.
Participants received radiotherapy once daily (OD), with a dose/fraction <2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Data are presented as of the cut-off date of 1-August-2014.
Adverse Event Reporting Description Data are presented for the Safety Population (SP)=participants (par.) who were randomized and took >=1 dose of study medication (SM). One par. randomized to placebo received lapatinib in error and was assigned to the lapatinib arm in the SP. One par. randomized to placebo withdrew from the study prior to receiving SM and was not included in the SP.
 
Arm/Group Title Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Hide Arm/Group Description Participants received radiotherapy once daily (OD), with a dose/fraction less than 2.5 Gray (Gy) to a total dose of 70 Gy (using two-dimensional [2D] or 3D techniques) or 65 Gy (using Intensity Modulated Radiation Therapy [IMRT]) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 milligrams per meters squared (mg/m^2) was administered intravenously (IV) on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Matching placebo administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, placebo monotherapy was administered until disease progression or withdrawal. Participants received radiotherapy once daily (OD), with a dose/fraction less than 2.5 Gy to a total dose of 70 Gy (using 2D or 3D techniques) or 65 Gy (using IMRT) to the gross site of disease. Concurrent chemotherapy of cisplatin 100 mg/m^2 was administered IV on Days 1, 22, and 43 of the course of radiotherapy (Study Days 8, 29, and 50). Lapatinib 1500 mg OD administration commenced 1 week (or less than or equal to 3 days) prior to the concurrent administration with chemoradiation for a duration of up to 6 to 7 weeks. After the completion of chemoradiotherapy, lapatinib 1500 mg OD monotherapy was administered until disease progression or withdrawal.
All-Cause Mortality
Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   18/31 (58.06%)   22/35 (62.86%) 
Blood and lymphatic system disorders     
Anemia  1  3/31 (9.68%)  2/35 (5.71%) 
Febrile Neutropenia  1  1/31 (3.23%)  2/35 (5.71%) 
Neutropenia  1  2/31 (6.45%)  2/35 (5.71%) 
Lymphopenia  1  0/31 (0.00%)  1/35 (2.86%) 
Pancytopenia  1  1/31 (3.23%)  0/35 (0.00%) 
Leukopenia  1  1/31 (3.23%)  0/35 (0.00%) 
Cardiac disorders     
Left Ventricular Dysfunction  1  1/31 (3.23%)  0/35 (0.00%) 
Myocardial Infarction  1  0/31 (0.00%)  1/35 (2.86%) 
Pericardial Effusion  1  0/31 (0.00%)  1/35 (2.86%) 
Gastrointestinal disorders     
Dysphagia  1  2/31 (6.45%)  2/35 (5.71%) 
Diarrhea  1  0/31 (0.00%)  3/35 (8.57%) 
Mouth Hemorrhage  1  1/31 (3.23%)  0/35 (0.00%) 
Parotid Gland Inflammation  1  1/31 (3.23%)  0/35 (0.00%) 
Vomiting  1  0/31 (0.00%)  1/35 (2.86%) 
General disorders     
Mucosal Inflammation  1  1/31 (3.23%)  3/35 (8.57%) 
Asthenia  1  1/31 (3.23%)  0/35 (0.00%) 
Death  1  0/31 (0.00%)  1/35 (2.86%) 
Fatigue  1  0/31 (0.00%)  1/35 (2.86%) 
Localised Edema  1  0/31 (0.00%)  1/35 (2.86%) 
Soft Tissue Inflammation  1  0/31 (0.00%)  1/35 (2.86%) 
Infections and infestations     
Pneumonia  1  3/31 (9.68%)  1/35 (2.86%) 
Bronchitis  1  0/31 (0.00%)  1/35 (2.86%) 
Gastrointestinal Infection  1  0/31 (0.00%)  1/35 (2.86%) 
Parotitis  1  1/31 (3.23%)  0/35 (0.00%) 
Pharyngitis  1  1/31 (3.23%)  0/35 (0.00%) 
Septic Shock  1  1/31 (3.23%)  0/35 (0.00%) 
Staphylococcal Infection  1  0/31 (0.00%)  1/35 (2.86%) 
Injury, poisoning and procedural complications     
Gastrostomy Failure  1  1/31 (3.23%)  0/35 (0.00%) 
Investigations     
Weight Decreased  1  2/31 (6.45%)  0/35 (0.00%) 
Creatinine Renal Clearance Decreased  1  0/31 (0.00%)  1/35 (2.86%) 
Ejection Fraction Decreased  1  1/31 (3.23%)  0/35 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  1/31 (3.23%)  3/35 (8.57%) 
Hyponatremia  1  1/31 (3.23%)  1/35 (2.86%) 
Decreased Appetite  1  0/31 (0.00%)  1/35 (2.86%) 
Hyperuricemia  1  0/31 (0.00%)  1/35 (2.86%) 
Malnutrition  1  0/31 (0.00%)  1/35 (2.86%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumor Hemorrhage  1  2/31 (6.45%)  0/35 (0.00%) 
Metastatic Neoplasm  1  0/31 (0.00%)  1/35 (2.86%) 
Squamous cell carcinoma of the tongue  1  0/31 (0.00%)  1/35 (2.86%) 
Nervous system disorders     
Cerebrovascular Accident  1  1/31 (3.23%)  0/35 (0.00%) 
Quadriparesis  1  0/31 (0.00%)  1/35 (2.86%) 
Somnolence  1  0/31 (0.00%)  1/35 (2.86%) 
Syncope  1  1/31 (3.23%)  0/35 (0.00%) 
Dizziness  1  0/31 (0.00%)  1/35 (2.86%) 
Hemiparesis  1  0/31 (0.00%)  1/35 (2.86%) 
Hypoaesthesia  1  0/31 (0.00%)  1/35 (2.86%) 
Renal and urinary disorders     
Renal Tubular Disorder  1  0/31 (0.00%)  2/35 (5.71%) 
Renal Failure  1  0/31 (0.00%)  1/35 (2.86%) 
Renal Failure Acute  1  0/31 (0.00%)  1/35 (2.86%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  2/31 (6.45%)  1/35 (2.86%) 
Pneumonia Aspiration  1  1/31 (3.23%)  1/35 (2.86%) 
Aspiration  1  1/31 (3.23%)  0/35 (0.00%) 
Lung Disorder  1  1/31 (3.23%)  0/35 (0.00%) 
Obstructive Airways Disorder  1  1/31 (3.23%)  0/35 (0.00%) 
Pharyngeal Ulceration  1  1/31 (3.23%)  0/35 (0.00%) 
Respiratory Distress  1  0/31 (0.00%)  1/35 (2.86%) 
Respiratory Failure  1  1/31 (3.23%)  0/35 (0.00%) 
Stridor  1  1/31 (3.23%)  0/35 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  0/31 (0.00%)  1/35 (2.86%) 
Vascular disorders     
Hemorrhage  1  1/31 (3.23%)  1/35 (2.86%) 
Arterial Occlusive Disease  1  0/31 (0.00%)  1/35 (2.86%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Chemoradiotherapy + Placebo, Followed by Placebo Chemoradiotherapy + Lapatinib, Followed by Lapatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   31/31 (100.00%)   34/35 (97.14%) 
Blood and lymphatic system disorders     
Neutropenia  1  13/31 (41.94%)  7/35 (20.00%) 
Anemia  1  11/31 (35.48%)  9/35 (25.71%) 
Leukopenia  1  7/31 (22.58%)  5/35 (14.29%) 
Thrombocytopenia  1  4/31 (12.90%)  1/35 (2.86%) 
Lymphopenia  1  2/31 (6.45%)  1/35 (2.86%) 
Leukocytosis  1  0/31 (0.00%)  2/35 (5.71%) 
Congenital, familial and genetic disorders     
Aplasia  1  2/31 (6.45%)  0/35 (0.00%) 
Ear and labyrinth disorders     
Tinnitus  1  3/31 (9.68%)  6/35 (17.14%) 
Ear Pain  1  4/31 (12.90%)  2/35 (5.71%) 
Hypoacusis  1  0/31 (0.00%)  3/35 (8.57%) 
Vertigo  1  0/31 (0.00%)  2/35 (5.71%) 
Gastrointestinal disorders     
Nausea  1  17/31 (54.84%)  22/35 (62.86%) 
Dry Mouth  1  13/31 (41.94%)  15/35 (42.86%) 
Vomiting  1  10/31 (32.26%)  14/35 (40.00%) 
Constipation  1  13/31 (41.94%)  9/35 (25.71%) 
Diarrhea  1  2/31 (6.45%)  18/35 (51.43%) 
Dysphagia  1  11/31 (35.48%)  10/35 (28.57%) 
Odynophagia  1  9/31 (29.03%)  7/35 (20.00%) 
Oral Pain  1  8/31 (25.81%)  7/35 (20.00%) 
Stomatitis  1  6/31 (19.35%)  5/35 (14.29%) 
Dyspepsia  1  2/31 (6.45%)  4/35 (11.43%) 
Gastroesophageal Reflux Disease  1  3/31 (9.68%)  2/35 (5.71%) 
Aptyalism  1  1/31 (3.23%)  2/35 (5.71%) 
Mouth Ulceration  1  1/31 (3.23%)  3/35 (8.57%) 
Salivary Gland Disorder  1  2/31 (6.45%)  2/35 (5.71%) 
Aphagia  1  1/31 (3.23%)  2/35 (5.71%) 
Cheilitis  1  1/31 (3.23%)  2/35 (5.71%) 
Tongue Ulceration  1  0/31 (0.00%)  3/35 (8.57%) 
Glossitis  1  0/31 (0.00%)  2/35 (5.71%) 
Proctalgia  1  2/31 (6.45%)  0/35 (0.00%) 
Oral mucosal erythema  1  0/31 (0.00%)  2/35 (5.71%) 
General disorders     
Mucosal Inflammation  1  14/31 (45.16%)  14/35 (40.00%) 
Asthenia  1  14/31 (45.16%)  4/35 (11.43%) 
Pyrexia  1  6/31 (19.35%)  11/35 (31.43%) 
Localized Edema  1  7/31 (22.58%)  4/35 (11.43%) 
Fatigue  1  2/31 (6.45%)  6/35 (17.14%) 
Pain  1  3/31 (9.68%)  3/35 (8.57%) 
Edema Peripheral  1  3/31 (9.68%)  2/35 (5.71%) 
Chills  1  1/31 (3.23%)  2/35 (5.71%) 
Face Edema  1  1/31 (3.23%)  2/35 (5.71%) 
Fibrosis  1  0/31 (0.00%)  2/35 (5.71%) 
Influenza Like Illness  1  0/31 (0.00%)  2/35 (5.71%) 
Non-Cardiac Chest Pain  1  0/31 (0.00%)  2/35 (5.71%) 
Infections and infestations     
Oral Candidiasis  1  6/31 (19.35%)  4/35 (11.43%) 
Oral Fungal Infection  1  5/31 (16.13%)  3/35 (8.57%) 
Oral Infection  1  2/31 (6.45%)  2/35 (5.71%) 
Upper Respiratory Tract Infection  1  3/31 (9.68%)  1/35 (2.86%) 
Bronchitis  1  1/31 (3.23%)  2/35 (5.71%) 
Influenza  1  2/31 (6.45%)  1/35 (2.86%) 
Nasopharyngitis  1  1/31 (3.23%)  2/35 (5.71%) 
Candidiasis  1  2/31 (6.45%)  0/35 (0.00%) 
Catheter Site Infection  1  2/31 (6.45%)  0/35 (0.00%) 
Infection  1  0/31 (0.00%)  2/35 (5.71%) 
Rhinitis  1  1/31 (3.23%)  2/35 (5.71%) 
Conjunctivitis  1  0/31 (0.00%)  2/35 (5.71%) 
Dental caries  1  0/31 (0.00%)  2/35 (5.71%) 
Fungal infection  1  2/31 (6.45%)  1/35 (2.86%) 
Sinusitis  1  0/31 (0.00%)  2/35 (5.71%) 
Injury, poisoning and procedural complications     
Radiation Skin Injury  1  9/31 (29.03%)  5/35 (14.29%) 
Radiation Mucositis  1  5/31 (16.13%)  4/35 (11.43%) 
Procedural Pain  1  3/31 (9.68%)  0/35 (0.00%) 
Investigations     
Weight Decreased  1  12/31 (38.71%)  11/35 (31.43%) 
Hemoglobin Decreased  1  7/31 (22.58%)  7/35 (20.00%) 
Creatinine Renal Clearance Decreased  1  4/31 (12.90%)  6/35 (17.14%) 
Blood Creatinine Increased  1  8/31 (25.81%)  2/35 (5.71%) 
Aspartate Aminotransferase Increased  1  7/31 (22.58%)  1/35 (2.86%) 
Alanine Aminotransferase Increased  1  3/31 (9.68%)  4/35 (11.43%) 
Blood Bilirubin Increased  1  3/31 (9.68%)  2/35 (5.71%) 
Blood Sodium Decreased  1  1/31 (3.23%)  2/35 (5.71%) 
Blood Urea Increased  1  2/31 (6.45%)  1/35 (2.86%) 
Neutrophil Count Increased  1  3/31 (9.68%)  2/35 (5.71%) 
Ejection Fraction Decreased  1  0/31 (0.00%)  2/35 (5.71%) 
Gamma Glutamyltransferase Increased  1  0/31 (0.00%)  2/35 (5.71%) 
White blood cell count decreased  1  2/31 (6.45%)  1/35 (2.86%) 
Metabolism and nutrition disorders     
Hypokalemia  1  4/31 (12.90%)  7/35 (20.00%) 
Decreased Appetite  1  6/31 (19.35%)  4/35 (11.43%) 
Hyponatremia  1  5/31 (16.13%)  4/35 (11.43%) 
Dehydration  1  3/31 (9.68%)  0/35 (0.00%) 
Hyperglycemia  1  2/31 (6.45%)  1/35 (2.86%) 
Gout  1  0/31 (0.00%)  2/35 (5.71%) 
Hyperkalemia  1  2/31 (6.45%)  0/35 (0.00%) 
Musculoskeletal and connective tissue disorders     
Neck Pain  1  6/31 (19.35%)  4/35 (11.43%) 
Back Pain  1  3/31 (9.68%)  1/35 (2.86%) 
Trismus  1  1/31 (3.23%)  2/35 (5.71%) 
Nervous system disorders     
Dysgeusia  1  8/31 (25.81%)  5/35 (14.29%) 
Headache  1  6/31 (19.35%)  6/35 (17.14%) 
Dizziness  1  2/31 (6.45%)  3/35 (8.57%) 
Paraesthesia  1  2/31 (6.45%)  3/35 (8.57%) 
Aphonia  1  2/31 (6.45%)  0/35 (0.00%) 
Lethargy  1  2/31 (6.45%)  0/35 (0.00%) 
Psychiatric disorders     
Anxiety  1  4/31 (12.90%)  5/35 (14.29%) 
Insomnia  1  2/31 (6.45%)  4/35 (11.43%) 
Depressed Mood  1  2/31 (6.45%)  1/35 (2.86%) 
Depression  1  0/31 (0.00%)  2/35 (5.71%) 
Renal and urinary disorders     
Renal Failure  1  4/31 (12.90%)  1/35 (2.86%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal Pain  1  7/31 (22.58%)  11/35 (31.43%) 
Dysphonia  1  6/31 (19.35%)  5/35 (14.29%) 
Cough  1  4/31 (12.90%)  4/35 (11.43%) 
Dyspnea  1  3/31 (9.68%)  2/35 (5.71%) 
Laryngeal Edema  1  2/31 (6.45%)  3/35 (8.57%) 
Epiglottic Edema  1  4/31 (12.90%)  0/35 (0.00%) 
Hemoptysis  1  2/31 (6.45%)  2/35 (5.71%) 
Increased Upper Airway Secretion  1  3/31 (9.68%)  1/35 (2.86%) 
Increased Viscosity of Bronchial Secretion  1  2/31 (6.45%)  2/35 (5.71%) 
Productive Cough  1  1/31 (3.23%)  2/35 (5.71%) 
Skin and subcutaneous tissue disorders     
Rash  1  8/31 (25.81%)  17/35 (48.57%) 
Skin Reaction  1  5/31 (16.13%)  8/35 (22.86%) 
Pruritus  1  2/31 (6.45%)  3/35 (8.57%) 
Dry Skin  1  1/31 (3.23%)  3/35 (8.57%) 
Nail Disorder  1  0/31 (0.00%)  2/35 (5.71%) 
Swelling face  1  0/31 (0.00%)  2/35 (5.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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.
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
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00387127     History of Changes
Other Study ID Numbers: EGF105884
First Submitted: October 10, 2006
First Posted: October 12, 2006
Results First Submitted: November 6, 2014
Results First Posted: January 5, 2015
Last Update Posted: June 25, 2015