Lapatinib Versus Placebo Given Concurrently With Cisplatin And Radiotherapy In Patients With Unresected Head And Neck Cancer
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT00387127
Collaborator
(none)
67
30
2
86
2.2
0
Study Details
Study Description
Brief Summary
This is a phase II study comparing the effects of lapatinib versus placebo when administered concurrently with cisplatin and radiotherapy followed by 1 year monotherapy with lapatinib or placebo. The study is designed to evaluate and compare the two treatment groups with respect to complete response rate at 6 months following chemoradiation completion.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
67 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo Controlled, Multicentre, Phase II Study of Oral Lapatinib in Combination With Concurrent Radiotherapy and Cisplatin Versus Radiotherapy and Cisplatin Alone, in Subjects With Stage III, IVA, B Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Study Start Date
:
Nov 1, 2006
Actual Primary Completion Date
:
Jun 1, 2009
Actual Study Completion Date
:
Jan 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lapatinib 1500mg lapatinib orally daily |
Drug: Lapatinib oral tablets
Lapatinib is administered orally once daily.
Drug: radiotherapy
Radiotherapy is given either as conventional fractionation using Two-dimensional (2D) or conformal techniques, or as Intensity Modulated Radiation Therapy (IMRT). Radiation therapy will be standardised throughout the study. Radiation therapy is given only once daily, with a dose/fraction not exceeding 2.5Gy, to a total dose of 65 Gy (IMRT) or 70 Gy (2D or 3D RT) to the gross site of disease .
Drug: cisplatin chemotherapy
Cisplatin is administered intravenously at a dose of 100mg/m2 on days 1, 22 and 43 of radiotherapy (approximately Study Days 8, 29 and 50).
Other Names:
|
| Placebo Comparator: Placebo orally daily |
Drug: Lapatinib oral tablets
Lapatinib is administered orally once daily.
Drug: radiotherapy
Radiotherapy is given either as conventional fractionation using Two-dimensional (2D) or conformal techniques, or as Intensity Modulated Radiation Therapy (IMRT). Radiation therapy will be standardised throughout the study. Radiation therapy is given only once daily, with a dose/fraction not exceeding 2.5Gy, to a total dose of 65 Gy (IMRT) or 70 Gy (2D or 3D RT) to the gross site of disease .
Drug: cisplatin chemotherapy
Cisplatin is administered intravenously at a dose of 100mg/m2 on days 1, 22 and 43 of radiotherapy (approximately Study Days 8, 29 and 50).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants (Par.) With Complete Response (CR), as Assessed by Independent Radiological Review [From the date of randomization until 6 months post chemoradiation treatment, assessed for a median time of 13 months]
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.
Secondary Outcome Measures
- Number of Participants With CR, as Assessed by the Investigator [From the date of randomization until 6 months post chemoradiation treatment, assessed after a median time of 13 months of follow-up]
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.
- Progression-Free Survival (PFS), as Assessed by the Investigator [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]
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.
- Overall Survival (OS) [From the date of randomization until the date of death due to any cause, assessed after a median of 30.9 months]
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.
- Number of Participants Who Died Due to Progressive Disease [From the date of randomization until the date of death due to disease under study, assessed after a median of 30.9 months]
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.
- Disease-specific Survival [From the date of randomization until the date of death due to disease, assessed after a median of 13 months of follow-up]
Disease-specific survival is defined as the time from randomization until death due to head and neck cancer.
- Number of Participants With Loco-regional Recurrence of Initial Disease [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]
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.
- Loco-regional Control [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]
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.
- Number of Participants With Distant Recurrence of Initial Disease [From the date of randomization until the first occurrence of distant metastasis, assessed after a median of 30.9 months]
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.
- Distant Relapse [From the date of randomization until the first occurrence of distant metastasis, assessed after a median of 30.9 months]
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.
- Number of Participants With Overall Response (OR), as Assessed by the Investigator [From the date of randomization until 6 months post chemoradiation treatment, assessed for a median of 13 months]
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.
- 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) [Up to 28 days prior to the date of the first dose of lapatinib/placebo start]
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.
- Plasma Proteome Analysis [From up to 28 days prior to the first dose of lapatinib/placebo start to 8 weeks after the first dose]
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.
- Analysis of Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) From Tumor Samples [Screening]
No analysis was performed for tumor sample RNA/DNA.
- Number of Participants Negative and Positive for Human Papilloma Virus (HPV) Infection, as Determined From Tumor Samples [Up to 28 days prior to the first dose of lapatinib/placebo]
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.
- 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) [From the date of randomization until 6 months post chemoradiation treatment, assessed for up to 24 weeks]
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).
- 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 [From the date of randomization until 6 months post chemoradiation treatment, assessed for up to 24 weeks]
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).
Other Outcome Measures
- Number of Participants Classified as Responders, as Per Volumetric Tumor Response [From the date of randomization until 6 months post chemoradiation treatment, assessed for a median of 13 months]
No analysis was not performed.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
-
Willing and able to sign a written informed consent;
-
Histologically confirmed diagnosis of SCCHN of one or more of the following sites:
oral cavity, oropharynx, hypopharynx and larynx;
Multiple primary tumours will:
Have to be histologically proven; Have to be anatomically distant and surrounded by normal tissue; Exclude distant metastasis.
-
Prior to enrolment subjects must have ErbB1 over-expression determined by immunohistochemistry (IHC) 3+ as assessed by a central laboratory;
-
Subjects with stage III and IVA/IVB disease, who are to receive cisplatin chemotherapy and radiation therapy as primary treatment (total dose 65 - 70 Gy); Subjects with any Tis, T1 or T2 disease regardless of N stage, are excluded. Subjects with distant metastases, ie Stage IVC, are excluded.
-
Willing and able to have a tumour biopsy taken at screening; For patients who have had prior tumour biopsy, an adequate archived specimen must be available.
-
Male or female ≥18 years of age;
Criteria for female subjects or female partners of male subjects:
Non-child-bearing potential (i.e., women with functioning ovaries who have a GM2005/00448/00 CONFIDENTIAL EGF105884 22 current documented tubal ligation or hysterectomy, or women who are postmenopausal); Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or Consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; implants of levonorgestrel; injectable progestogen; any intrauterine device (IUD) with a documented failure rate of less than
1% per year; oral contraceptives (either combined or progestogen only); or barrier methods, including diaphragm or condom with a spermicide.
-
ECOG performance status 0, 1 or 2;
-
Subjects must have adequate haematological, renal and hepatic function; Calculated creatinine clearance ≥50 ml/min as determined by the modified method of Cockcroft and Gault or by the EDTA method. Absolute neutrophil count ≥1,500/μl, platelets ≥100,000/μl. Haemoglobin ≥9gm/dL (5mmol/L). Aspartate (AST) and alanine transaminase (ALT) less than 4 times the upper limit of the normal range (ULN). Total bilirubin ≤2.0 mg/dL.
-
Left ventricular ejection fraction (LVEF) within the institutional normal ranges as measured by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan;
-
Able to swallow tablets whole or swallow a suspension of tablets dissolved in water at study inclusion; The use and timing of feeding tube is optional. If necessary, the suspension may be administered via percutaneous endoscopic gastrostomy (PEG), percutaneous jejunostomy tube (J- Tube), or a nasogastric tube (NG or Dobhoff type tube).
-
Life expectancy of at least 6 months in the best judgment of the investigator.
Exclusion criteria:
-
Nasopharyngeal, paranasal sinuses or nasal cavity tumours;
-
Any prior or current treatment for invasive head and neck cancer of any kind. This will include but is not limited to: prior tyrosine kinase inhibitors, prior neoadjuvant therapy, prior surgical resection, or use of any investigational agent;
-
Concurrent use of CYP3A4 inducers or inhibitors. A standard 3-day course of dexamethasone for the prevention of cisplatin-induced nausea and vomiting is permitted;
-
Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
-
History of another malignancy within the last 5 years, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma. History of non-invasive lesion or in-situ carcinoma, including in the head and neck region that was successfully treated with surgery, photodynamics or laser, will be permitted;
-
Peripheral neuropathy ≥ grade 2;
-
Pregnant or lactating females (female subjects of child-bearing potential will undertake pregnancy testing at screening and during study completion/withdrawal visits);
-
Malabsorption syndrome, disease significantly affecting GI function, that could affect absorption of lapatinib;
-
History of allergic reactions to appropriate antiemetics (e.g. 5-HT3 antagonists) to be administered with platinum chemotherapy;
-
The investigator considers the subject unfit for the study as a result of the medical interview, physical examinations, or screening investigations;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Minneapolis | Minnesota | United States | 55417 |
| 2 | GSK Investigational Site | Kansas City | Missouri | United States | 64128 |
| 3 | GSK Investigational Site | Charlotte | North Carolina | United States | 28203 |
| 4 | GSK Investigational Site | Hamilton | Ontario | Canada | L8V 5C2 |
| 5 | GSK Investigational Site | Sherbrooke | Quebec | Canada | J1H 5N4 |
| 6 | GSK Investigational Site | Quebec | Canada | G1R 2J6 | |
| 7 | GSK Investigational Site | Lens | France | 62307 | |
| 8 | GSK Investigational Site | Lille | France | 59000 | |
| 9 | GSK Investigational Site | Lyon | France | 69437 | |
| 10 | GSK Investigational Site | Paris cedex 15 | France | 75908 | |
| 11 | GSK Investigational Site | Vandoeuvre-Les-Nancy | France | 54511 | |
| 12 | GSK Investigational Site | Budapest | Hungary | 1122 | |
| 13 | GSK Investigational Site | Győr | Hungary | 9023 | |
| 14 | GSK Investigational Site | Ahemdabad | India | 380016 | |
| 15 | GSK Investigational Site | Mumbai | India | 400012 | |
| 16 | GSK Investigational Site | Thiruvananthapuram | India | 695011 | |
| 17 | GSK Investigational Site | Amsterdam | Netherlands | 1066 CX | |
| 18 | GSK Investigational Site | Leiden | Netherlands | 2333 ZA | |
| 19 | GSK Investigational Site | Lima | Peru | Lima 11 | |
| 20 | GSK Investigational Site | Lima | Peru | Lima 34 | |
| 21 | GSK Investigational Site | Barcelona | Spain | 08035 | |
| 22 | GSK Investigational Site | Madrid | Spain | 28041 | |
| 23 | GSK Investigational Site | Cambridge | Cambridgeshire | United Kingdom | CB2 0QQ |
| 24 | GSK Investigational Site | Northwood | Middlesex | United Kingdom | HA6 2RN |
| 25 | GSK Investigational Site | Coventry | United Kingdom | CV2 2DX | |
| 26 | GSK Investigational Site | Leeds | United Kingdom | LS9 7TF | |
| 27 | GSK Investigational Site | London | United Kingdom | EC1A 7BE | |
| 28 | GSK Investigational Site | London | United Kingdom | SW3 6JJ | |
| 29 | GSK Investigational Site | Newcastle upon Tyne | United Kingdom | NE7 7DN | |
| 30 | GSK Investigational Site | Sheffield | United Kingdom | S10 2SJ |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00387127
Other Study ID Numbers:
- EGF105884
First Posted:
Oct 12, 2006
Last Update Posted:
Jun 25, 2015
Last Verified:
Feb 1, 2015
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib | Total |
|---|---|---|---|
| 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 Participants | 33 | 34 | 67 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
56.5
(6.61)
|
55.8
(5.73)
|
56.1
(6.15)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
6.1%
|
5
14.7%
|
7
10.4%
|
| Male |
31
93.9%
|
29
85.3%
|
60
89.6%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| African American/African Heritage |
0
0%
|
1
2.9%
|
1
1.5%
|
| American Indian or Alaska Native |
2
6.1%
|
2
5.9%
|
4
6%
|
| Asian - Central/South Asian Heritage |
3
9.1%
|
6
17.6%
|
9
13.4%
|
| Asian - South East Asian Heritage |
2
6.1%
|
1
2.9%
|
3
4.5%
|
| White - White/Caucasian/European Heritage |
26
78.8%
|
24
70.6%
|
50
74.6%
|
Outcome Measures
| Title | Number of Participants (Par.) With Complete Response (CR), as Assessed by Independent Radiological Review |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Number [Participants] |
12
36.4%
|
18
52.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Chemoradiotherapy + Placebo, Followed by Placebo, Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3658 |
| Comments | From exact test that common odds ratio equals 1 | |
| Method | Fisher Exact | |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Complete response was defined as the percentage of participants achieving a CR as determined by an independent radiological review. | |
| Title | Number of Participants With CR, as Assessed by the Investigator |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Number [Participants] |
7
21.2%
|
17
50%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Chemoradiotherapy + Placebo, Followed by Placebo, Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0130 |
| Comments | From exact test that common odds ratio equals 1 | |
| Method | Fisher Exact | |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Complete response was defined as the percentage of participants achieving a CR as determined by the investigator. | |
| Title | Progression-Free Survival (PFS), as Assessed by the Investigator |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Median (95% Confidence Interval) [Months] |
12.1
|
20.4
|
| Title | Overall Survival (OS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Median (95% Confidence Interval) [Months] |
23.0
|
48.4
|
| Title | Number of Participants Who Died Due to Progressive Disease |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Number [Participants] |
11
33.3%
|
8
23.5%
|
| Title | Disease-specific Survival |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Median (Inter-Quartile Range) [Months] |
NA
|
NA
|
| Title | Number of Participants With Loco-regional Recurrence of Initial Disease |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Number [Participants] |
7
21.2%
|
4
11.8%
|
| Title | Loco-regional Control |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| Title | Number of Participants With Distant Recurrence of Initial Disease |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Number [Participants] |
5
15.2%
|
8
23.5%
|
| Title | Distant Relapse |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Median (Inter-Quartile Range) [Months] |
NA
|
NA
|
| Title | Number of Participants With Overall Response (OR), as Assessed by the Investigator |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Number [Participants] |
15
45.5%
|
21
61.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Chemoradiotherapy + Placebo, Followed by Placebo, Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1969 |
| Comments | From exact test that common odds ratio equals 1 | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in overall response rate |
| Estimated Value | 16.3 | |
| Confidence Interval |
(2-Sided) 95% -8.6 to 42.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Overall response was defined as the percentage of participants achieving a PR or CR as determined by the investigator. | |
| 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) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 30 | 27 |
| HER1, Positive, n=27, 24 |
27
81.8%
|
19
55.9%
|
| HER1, Negative, n=27, 24 |
0
0%
|
5
14.7%
|
| HER2, Positive, n=26, 25 |
3
9.1%
|
0
0%
|
| HER2, Negative, n=26, 25 |
23
69.7%
|
24
70.6%
|
| HER2, Missing, n=26, 25 |
0
0%
|
1
2.9%
|
| HER3, Positive, n=27, 22 |
8
24.2%
|
5
14.7%
|
| HER3, Negative, n=27, 22 |
18
54.5%
|
16
47.1%
|
| HER3, Missing, n=27, 22 |
1
3%
|
1
2.9%
|
| HER4, Positive, n=26, 25 |
0
0%
|
0
0%
|
| HER4, Negative, n=26, 25 |
26
78.8%
|
24
70.6%
|
| HER4, Missing, n=26, 25 |
0
0%
|
1
2.9%
|
| P16 Positive, n=23, 23 |
3
9.1%
|
4
11.8%
|
| P16, Negative, n=23, 23 |
20
60.6%
|
19
55.9%
|
| TGF-alpha, Positive, n=24, 25 |
7
21.2%
|
4
11.8%
|
| TGF-alpha, Negative, n=24, 25 |
17
51.5%
|
20
58.8%
|
| TGF-alpha, Missing, n=24, 25 |
0
0%
|
1
2.9%
|
| Title | Plasma Proteome Analysis |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| Title | Analysis of Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) From Tumor Samples |
|---|---|
| Description | No analysis was performed for tumor sample RNA/DNA. |
| Time Frame | Screening |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
| Title | Number of Participants Negative and Positive for Human Papilloma Virus (HPV) Infection, as Determined From Tumor Samples |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Negative |
20
60.6%
|
19
55.9%
|
| Positive |
3
9.1%
|
4
11.8%
|
| Unknown |
10
30.3%
|
11
32.4%
|
| 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) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 27 | 24 |
| Negative, CR |
0
0%
|
0
0%
|
| Negative, PR |
0
0%
|
0
0%
|
| Negative, SD |
0
0%
|
0
0%
|
| Negative, PD (Week 24) |
0
0%
|
0
0%
|
| Negative, PD or Death (prior to Week 24) |
0
0%
|
0
0%
|
| Negative, Not Evaluable |
0
0%
|
0
0%
|
| Negative, Unknown |
0
0%
|
0
0%
|
| Positive, CR |
9
27.3%
|
14
41.2%
|
| Positive, PR |
4
12.1%
|
3
8.8%
|
| Positive, SD |
0
0%
|
0
0%
|
| Positive, PD (Week 24) |
4
12.1%
|
1
2.9%
|
| Positive, PD or Death (prior to Week 24) |
5
15.2%
|
4
11.8%
|
| Positive, Not Evaluable |
1
3%
|
0
0%
|
| Positive, Unknown |
4
12.1%
|
2
5.9%
|
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 33 | 34 |
| Negative, CR |
5
15.2%
|
9
26.5%
|
| Negative, PR |
2
6.1%
|
2
5.9%
|
| Negative, SD |
0
0%
|
0
0%
|
| Negative, PD (Week 24) |
1
3%
|
0
0%
|
| Negative, PD or Death (prior to Week 24) |
2
6.1%
|
4
11.8%
|
| Negative, Not Evaluable |
0
0%
|
0
0%
|
| Negative, Unknown |
1
3%
|
1
2.9%
|
| Positive, CR |
4
12.1%
|
5
14.7%
|
| Positive, PR |
2
6.1%
|
1
2.9%
|
| Positive, SD |
0
0%
|
0
0%
|
| Positive, PD (Week 24) |
3
9.1%
|
1
2.9%
|
| Positive, PD or Death (prior to Week 24) |
3
9.1%
|
0
0%
|
| Positive, Not Evaluable |
1
3%
|
0
0%
|
| Positive, Unknown |
3
9.1%
|
1
2.9%
|
| Title | Number of Participants Classified as Responders, as Per Volumetric Tumor Response |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 0 | 0 |
Adverse Events
| 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 | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/31 (58.1%) | 22/35 (62.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 3/31 (9.7%) | 2/35 (5.7%) | ||
| Febrile Neutropenia | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Neutropenia | 2/31 (6.5%) | 2/35 (5.7%) | ||
| Lymphopenia | 0/31 (0%) | 1/35 (2.9%) | ||
| Pancytopenia | 1/31 (3.2%) | 0/35 (0%) | ||
| Leukopenia | 1/31 (3.2%) | 0/35 (0%) | ||
| Cardiac disorders | ||||
| Left Ventricular Dysfunction | 1/31 (3.2%) | 0/35 (0%) | ||
| Myocardial Infarction | 0/31 (0%) | 1/35 (2.9%) | ||
| Pericardial Effusion | 0/31 (0%) | 1/35 (2.9%) | ||
| Gastrointestinal disorders | ||||
| Dysphagia | 2/31 (6.5%) | 2/35 (5.7%) | ||
| Diarrhea | 0/31 (0%) | 3/35 (8.6%) | ||
| Mouth Hemorrhage | 1/31 (3.2%) | 0/35 (0%) | ||
| Parotid Gland Inflammation | 1/31 (3.2%) | 0/35 (0%) | ||
| Vomiting | 0/31 (0%) | 1/35 (2.9%) | ||
| General disorders | ||||
| Mucosal Inflammation | 1/31 (3.2%) | 3/35 (8.6%) | ||
| Asthenia | 1/31 (3.2%) | 0/35 (0%) | ||
| Death | 0/31 (0%) | 1/35 (2.9%) | ||
| Fatigue | 0/31 (0%) | 1/35 (2.9%) | ||
| Localised Edema | 0/31 (0%) | 1/35 (2.9%) | ||
| Soft Tissue Inflammation | 0/31 (0%) | 1/35 (2.9%) | ||
| Infections and infestations | ||||
| Pneumonia | 3/31 (9.7%) | 1/35 (2.9%) | ||
| Bronchitis | 0/31 (0%) | 1/35 (2.9%) | ||
| Gastrointestinal Infection | 0/31 (0%) | 1/35 (2.9%) | ||
| Parotitis | 1/31 (3.2%) | 0/35 (0%) | ||
| Pharyngitis | 1/31 (3.2%) | 0/35 (0%) | ||
| Septic Shock | 1/31 (3.2%) | 0/35 (0%) | ||
| Staphylococcal Infection | 0/31 (0%) | 1/35 (2.9%) | ||
| Injury, poisoning and procedural complications | ||||
| Gastrostomy Failure | 1/31 (3.2%) | 0/35 (0%) | ||
| Investigations | ||||
| Weight Decreased | 2/31 (6.5%) | 0/35 (0%) | ||
| Creatinine Renal Clearance Decreased | 0/31 (0%) | 1/35 (2.9%) | ||
| Ejection Fraction Decreased | 1/31 (3.2%) | 0/35 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/31 (3.2%) | 3/35 (8.6%) | ||
| Hyponatremia | 1/31 (3.2%) | 1/35 (2.9%) | ||
| Decreased Appetite | 0/31 (0%) | 1/35 (2.9%) | ||
| Hyperuricemia | 0/31 (0%) | 1/35 (2.9%) | ||
| Malnutrition | 0/31 (0%) | 1/35 (2.9%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumor Hemorrhage | 2/31 (6.5%) | 0/35 (0%) | ||
| Metastatic Neoplasm | 0/31 (0%) | 1/35 (2.9%) | ||
| Squamous cell carcinoma of the tongue | 0/31 (0%) | 1/35 (2.9%) | ||
| Nervous system disorders | ||||
| Cerebrovascular Accident | 1/31 (3.2%) | 0/35 (0%) | ||
| Quadriparesis | 0/31 (0%) | 1/35 (2.9%) | ||
| Somnolence | 0/31 (0%) | 1/35 (2.9%) | ||
| Syncope | 1/31 (3.2%) | 0/35 (0%) | ||
| Dizziness | 0/31 (0%) | 1/35 (2.9%) | ||
| Hemiparesis | 0/31 (0%) | 1/35 (2.9%) | ||
| Hypoaesthesia | 0/31 (0%) | 1/35 (2.9%) | ||
| Renal and urinary disorders | ||||
| Renal Tubular Disorder | 0/31 (0%) | 2/35 (5.7%) | ||
| Renal Failure | 0/31 (0%) | 1/35 (2.9%) | ||
| Renal Failure Acute | 0/31 (0%) | 1/35 (2.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 2/31 (6.5%) | 1/35 (2.9%) | ||
| Pneumonia Aspiration | 1/31 (3.2%) | 1/35 (2.9%) | ||
| Aspiration | 1/31 (3.2%) | 0/35 (0%) | ||
| Lung Disorder | 1/31 (3.2%) | 0/35 (0%) | ||
| Obstructive Airways Disorder | 1/31 (3.2%) | 0/35 (0%) | ||
| Pharyngeal Ulceration | 1/31 (3.2%) | 0/35 (0%) | ||
| Respiratory Distress | 0/31 (0%) | 1/35 (2.9%) | ||
| Respiratory Failure | 1/31 (3.2%) | 0/35 (0%) | ||
| Stridor | 1/31 (3.2%) | 0/35 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 0/31 (0%) | 1/35 (2.9%) | ||
| Vascular disorders | ||||
| Hemorrhage | 1/31 (3.2%) | 1/35 (2.9%) | ||
| Arterial Occlusive Disease | 0/31 (0%) | 1/35 (2.9%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Chemoradiotherapy + Placebo, Followed by Placebo | Chemoradiotherapy + Lapatinib, Followed by Lapatinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 31/31 (100%) | 34/35 (97.1%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 13/31 (41.9%) | 7/35 (20%) | ||
| Anemia | 11/31 (35.5%) | 9/35 (25.7%) | ||
| Leukopenia | 7/31 (22.6%) | 5/35 (14.3%) | ||
| Thrombocytopenia | 4/31 (12.9%) | 1/35 (2.9%) | ||
| Lymphopenia | 2/31 (6.5%) | 1/35 (2.9%) | ||
| Leukocytosis | 0/31 (0%) | 2/35 (5.7%) | ||
| Congenital, familial and genetic disorders | ||||
| Aplasia | 2/31 (6.5%) | 0/35 (0%) | ||
| Ear and labyrinth disorders | ||||
| Tinnitus | 3/31 (9.7%) | 6/35 (17.1%) | ||
| Ear Pain | 4/31 (12.9%) | 2/35 (5.7%) | ||
| Hypoacusis | 0/31 (0%) | 3/35 (8.6%) | ||
| Vertigo | 0/31 (0%) | 2/35 (5.7%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 17/31 (54.8%) | 22/35 (62.9%) | ||
| Dry Mouth | 13/31 (41.9%) | 15/35 (42.9%) | ||
| Vomiting | 10/31 (32.3%) | 14/35 (40%) | ||
| Constipation | 13/31 (41.9%) | 9/35 (25.7%) | ||
| Diarrhea | 2/31 (6.5%) | 18/35 (51.4%) | ||
| Dysphagia | 11/31 (35.5%) | 10/35 (28.6%) | ||
| Odynophagia | 9/31 (29%) | 7/35 (20%) | ||
| Oral Pain | 8/31 (25.8%) | 7/35 (20%) | ||
| Stomatitis | 6/31 (19.4%) | 5/35 (14.3%) | ||
| Dyspepsia | 2/31 (6.5%) | 4/35 (11.4%) | ||
| Gastroesophageal Reflux Disease | 3/31 (9.7%) | 2/35 (5.7%) | ||
| Aptyalism | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Mouth Ulceration | 1/31 (3.2%) | 3/35 (8.6%) | ||
| Salivary Gland Disorder | 2/31 (6.5%) | 2/35 (5.7%) | ||
| Aphagia | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Cheilitis | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Tongue Ulceration | 0/31 (0%) | 3/35 (8.6%) | ||
| Glossitis | 0/31 (0%) | 2/35 (5.7%) | ||
| Proctalgia | 2/31 (6.5%) | 0/35 (0%) | ||
| Oral mucosal erythema | 0/31 (0%) | 2/35 (5.7%) | ||
| General disorders | ||||
| Mucosal Inflammation | 14/31 (45.2%) | 14/35 (40%) | ||
| Asthenia | 14/31 (45.2%) | 4/35 (11.4%) | ||
| Pyrexia | 6/31 (19.4%) | 11/35 (31.4%) | ||
| Localized Edema | 7/31 (22.6%) | 4/35 (11.4%) | ||
| Fatigue | 2/31 (6.5%) | 6/35 (17.1%) | ||
| Pain | 3/31 (9.7%) | 3/35 (8.6%) | ||
| Edema Peripheral | 3/31 (9.7%) | 2/35 (5.7%) | ||
| Chills | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Face Edema | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Fibrosis | 0/31 (0%) | 2/35 (5.7%) | ||
| Influenza Like Illness | 0/31 (0%) | 2/35 (5.7%) | ||
| Non-Cardiac Chest Pain | 0/31 (0%) | 2/35 (5.7%) | ||
| Infections and infestations | ||||
| Oral Candidiasis | 6/31 (19.4%) | 4/35 (11.4%) | ||
| Oral Fungal Infection | 5/31 (16.1%) | 3/35 (8.6%) | ||
| Oral Infection | 2/31 (6.5%) | 2/35 (5.7%) | ||
| Upper Respiratory Tract Infection | 3/31 (9.7%) | 1/35 (2.9%) | ||
| Bronchitis | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Influenza | 2/31 (6.5%) | 1/35 (2.9%) | ||
| Nasopharyngitis | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Candidiasis | 2/31 (6.5%) | 0/35 (0%) | ||
| Catheter Site Infection | 2/31 (6.5%) | 0/35 (0%) | ||
| Infection | 0/31 (0%) | 2/35 (5.7%) | ||
| Rhinitis | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Conjunctivitis | 0/31 (0%) | 2/35 (5.7%) | ||
| Dental caries | 0/31 (0%) | 2/35 (5.7%) | ||
| Fungal infection | 2/31 (6.5%) | 1/35 (2.9%) | ||
| Sinusitis | 0/31 (0%) | 2/35 (5.7%) | ||
| Injury, poisoning and procedural complications | ||||
| Radiation Skin Injury | 9/31 (29%) | 5/35 (14.3%) | ||
| Radiation Mucositis | 5/31 (16.1%) | 4/35 (11.4%) | ||
| Procedural Pain | 3/31 (9.7%) | 0/35 (0%) | ||
| Investigations | ||||
| Weight Decreased | 12/31 (38.7%) | 11/35 (31.4%) | ||
| Hemoglobin Decreased | 7/31 (22.6%) | 7/35 (20%) | ||
| Creatinine Renal Clearance Decreased | 4/31 (12.9%) | 6/35 (17.1%) | ||
| Blood Creatinine Increased | 8/31 (25.8%) | 2/35 (5.7%) | ||
| Aspartate Aminotransferase Increased | 7/31 (22.6%) | 1/35 (2.9%) | ||
| Alanine Aminotransferase Increased | 3/31 (9.7%) | 4/35 (11.4%) | ||
| Blood Bilirubin Increased | 3/31 (9.7%) | 2/35 (5.7%) | ||
| Blood Sodium Decreased | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Blood Urea Increased | 2/31 (6.5%) | 1/35 (2.9%) | ||
| Neutrophil Count Increased | 3/31 (9.7%) | 2/35 (5.7%) | ||
| Ejection Fraction Decreased | 0/31 (0%) | 2/35 (5.7%) | ||
| Gamma Glutamyltransferase Increased | 0/31 (0%) | 2/35 (5.7%) | ||
| White blood cell count decreased | 2/31 (6.5%) | 1/35 (2.9%) | ||
| Metabolism and nutrition disorders | ||||
| Hypokalemia | 4/31 (12.9%) | 7/35 (20%) | ||
| Decreased Appetite | 6/31 (19.4%) | 4/35 (11.4%) | ||
| Hyponatremia | 5/31 (16.1%) | 4/35 (11.4%) | ||
| Dehydration | 3/31 (9.7%) | 0/35 (0%) | ||
| Hyperglycemia | 2/31 (6.5%) | 1/35 (2.9%) | ||
| Gout | 0/31 (0%) | 2/35 (5.7%) | ||
| Hyperkalemia | 2/31 (6.5%) | 0/35 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Neck Pain | 6/31 (19.4%) | 4/35 (11.4%) | ||
| Back Pain | 3/31 (9.7%) | 1/35 (2.9%) | ||
| Trismus | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Nervous system disorders | ||||
| Dysgeusia | 8/31 (25.8%) | 5/35 (14.3%) | ||
| Headache | 6/31 (19.4%) | 6/35 (17.1%) | ||
| Dizziness | 2/31 (6.5%) | 3/35 (8.6%) | ||
| Paraesthesia | 2/31 (6.5%) | 3/35 (8.6%) | ||
| Aphonia | 2/31 (6.5%) | 0/35 (0%) | ||
| Lethargy | 2/31 (6.5%) | 0/35 (0%) | ||
| Psychiatric disorders | ||||
| Anxiety | 4/31 (12.9%) | 5/35 (14.3%) | ||
| Insomnia | 2/31 (6.5%) | 4/35 (11.4%) | ||
| Depressed Mood | 2/31 (6.5%) | 1/35 (2.9%) | ||
| Depression | 0/31 (0%) | 2/35 (5.7%) | ||
| Renal and urinary disorders | ||||
| Renal Failure | 4/31 (12.9%) | 1/35 (2.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Oropharyngeal Pain | 7/31 (22.6%) | 11/35 (31.4%) | ||
| Dysphonia | 6/31 (19.4%) | 5/35 (14.3%) | ||
| Cough | 4/31 (12.9%) | 4/35 (11.4%) | ||
| Dyspnea | 3/31 (9.7%) | 2/35 (5.7%) | ||
| Laryngeal Edema | 2/31 (6.5%) | 3/35 (8.6%) | ||
| Epiglottic Edema | 4/31 (12.9%) | 0/35 (0%) | ||
| Hemoptysis | 2/31 (6.5%) | 2/35 (5.7%) | ||
| Increased Upper Airway Secretion | 3/31 (9.7%) | 1/35 (2.9%) | ||
| Increased Viscosity of Bronchial Secretion | 2/31 (6.5%) | 2/35 (5.7%) | ||
| Productive Cough | 1/31 (3.2%) | 2/35 (5.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 8/31 (25.8%) | 17/35 (48.6%) | ||
| Skin Reaction | 5/31 (16.1%) | 8/35 (22.9%) | ||
| Pruritus | 2/31 (6.5%) | 3/35 (8.6%) | ||
| Dry Skin | 1/31 (3.2%) | 3/35 (8.6%) | ||
| Nail Disorder | 0/31 (0%) | 2/35 (5.7%) | ||
| Swelling face | 0/31 (0%) | 2/35 (5.7%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00387127
Other Study ID Numbers:
- EGF105884
First Posted:
Oct 12, 2006
Last Update Posted:
Jun 25, 2015
Last Verified:
Feb 1, 2015