A Study Of Lapatinib Versus Placebo Followed By Chemoradiation In Patients With Locally Advanced Head And Neck Cancer

Phase 2

Completed

• Conditions: Squamous Cell Carcinoma of Head and Neck
• Interventions: Drug: Lapatinib oral tablets; Drug: Placebo

• Registration Number: NCT00371566
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This is a study comparing the activity of lapatinib versus placebo followed by chemoradiation. This study is designed to explore the effects of lapatinib monotherapy on apoptosis/necrosis, in pre-treatment and post-treatment tumour tissue samples in subjects with locally advanced squamous cell carcinoma of head and neck.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-03
• Study First Submitted: 2006-08-31
• Study First Submitted QC: 2006-08-31
• Study First Posted: 2006-09-04
• Primary Completion: 2007-12
• Study Completion: 2007-12
• Results First Submitted: 2008-12-26
• Results First Submitted QC: 2010-01-06
• Results First Posted: 2010-01-29
• Status Verified: 2010-04
• Last Update Submitted: 2010-04-01
• Last Update Posted: 2010-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lapatinib	Lapatinib oral tablets	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline of the Apoptotic Index During Treatment Phase	Baseline and Week 2	Apoptotic Index-TUNEL Assay is a method which counts a total of at least 1000 neoplastic nuclei(Cells with morphological changes defining cell death) subdivided in 10 fields chosen randomly at 400x magnification. A 'responder' was defined as having 20% cell death.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline of Cell Proliferation Rate of the Ki-67 Proliferative Index in Tumour Biopsy Samples During Treatment Phase	Baseline and Week 2	The Ki-67 protein is expressed in all phases of the cell cycle except G0 (low level phase) and serves as a good marker for cell proliferation. Scoring is assessed by point counting 500 to 1000 cells, and is reported as percent positive cells. 20% positive cells to define "positive" (i.e. high risk)
Overall Radiological Response After Treatment Phase in mITT Population	Baseline and End of Treatment (Week 2 - 6)	Over all: Complete Response (CR)- absence of lesions. Partial Response (PR)- CR or PR of target lesions and incomplete response (IC) or stable disease (SD) in other lesions with no new lesions or progressive disease (PD). Stable Disease (SD)-no PD or Response. Progressive Disease (PD)-PD or new lesions. Not Evaluable(NE)- no other definitions. Number of subjects included those who had a scan immediately post lapatanib/placebo monotherapy.
Overall Radiological Response After Follow-up Phase in mITT Population	Baseline and End of Follow-up (Week 19 - 25)	Over all: Complete Response(CR)-absence of lesions. Partial Response(PR)- CR or PR of target lesions and incomplete response (IC) or stable disease (SD)in other lesions with no new lesions or progressive disease (PD). Stable Disease(SD)-no PD or Response. Progressive Disease(PD)-PD or new lesions. Not Evaluable(NE)- no other definitions. Number of subjects included those who were considered evaluable if they completed a full course of chemoradiotherapy and were able to provide a baseline and follow-up scan following the completion of chemoradiation.
Overall Radiological Response After Treatment Phase in ITT Population	Baseline and End of Treatment (Week 2 - 6)	Over all: Complete Response (CR)-absence of lesions. Partial Response (PR)- CR or PR of target lesions and incomplete response (IC) or stable disease (SD) in other lesions with no new lesions or progressive disease (PD). Stable Disease (SD)-no PD or Response. Progressive Disease (PD)-PD or new lesions. Not Evaluable(NE)- no other definitions.
Overall Radiological Response After Follow-up Phase in ITT Population	Baseline and End of Follow-up (week 19 - 25)	Over all: Complete Response (CR) - absence of lesions. Partial Response (PR) - CR or PR of target lesions and incomplete response (IC) or stable disease (SD) in other lesions with no new lesions or progressive disease (PD). Stable Disease (SD)- no PD or Response. Progressive Disease (PD)- PD or new lesions. Not Evaluable(NE)- no other definitions.
Number of Circulating Tumor Cells at Baseline in mITT Population	Baseline	This measures the participants with Circulating Tumor Cells (CTC's)Pre-Treatment numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.
Relative Change From Baseline of Kep Mean (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	DCE-MRI tracks the diffusion of an intravascularly administered contrast agent into the extravascular tissue over time. Over a period of time, the contrast agent diffuses back into the vasculature (described by the rate constant or Kep). The lower the Kep, the longer the contrast remains in the extravascular space and is more prolonged. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g., vessel permeability, etc.) are determined.
Relative Change From Baseline of Kep Perfused (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	DCE-MRI tracks the diffusion of an intravascularly administered contrast agent into the extravascular tissue over time. Over a period of time, the contrast agent diffuses back into the vasculature (described by the rate constant or Kep). The lower the Kep, the longer the contrast remains in the extravascular space and is more prolonged. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g., vessel permeability, etc.) are determined.
Relative Change From Baseline of Kep Whole (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	DCE-MRI tracks the diffusion of an intravascularly administered contrast agent into the extravascular tissue over time. Over a period of time, the contrast agent diffuses back into the vasculature (described by the rate constant or Kep). The lower the Kep, the longer the contrast remains in the extravascular space and is more prolonged. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g., vessel permeability, etc.) are determined.
Relative Change From Baseline of Ktrans Mean (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an administered contrast agent from -intra into the extravascular tissue over time. Ktrans estimates blood flow and relates to the ease of exchange into extravascular spaces. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g.,tissue perfusion, vessel permeability, vascular surface area, and extracellular/vascular volume fraction) are determined.
Relative Change From Baseline of Ktrans Perfused (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an administered contrast agent from -intra into the extravascular tissue over time. Ktrans estimates blood flow and relates to the ease of exchange into extravascular spaces. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g.,tissue perfusion, vessel permeability, vascular surface area, and extracellular/vascular volume fraction) are determined.
Number of Biomarkers Including Tumor Protein 53 and HPV During Treatment Phase	Week 2	Tumor Suppressor p53 is welcomed and described as "the guardian angel gene," it conserves stability by preventing genome mutation. Human Papillomavirus (HPV) biomarker is un-welcomed and is found to be an important precursor cancers of the head and neck. HPV biomarkers have the ability to bind to and inactivate the Tumor Suppressor p53 biomarker.
Number of Participants With Circulating Tumor Cells After Treatment Phase in mITT Population	End of Treatment (week 2 - 6)	This measures the participants with Circulating Tumor Cells (CTC's) after treatment numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.
Number of Participants With Circulating Tumor Cells After Chemoradiotherapy Phase in mITT Population	End of Chemoradiotherapy (week 10 - 13)	This measures the participants with Circulating Tumor Cells (CTC's) after chemoradiotherapy numbers of 0 to \>= 4. CTC's are tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors.
Number of Biomarkers Including ErbB1, ErbB2, pErbB1, and pErb2 at Baseline and During Treatment Phase	Baseline and Week 2	Estrogen Receptor (ER) variants, ERB-B2 and ERB B-5 consist of the major proportion of ER expression both in normal and cancer tissues. The exact role of these markers are unknown. Acronyms defined: ICH (immunohistochemical) and FISH (fluorescence in situ hybridization).
Summary of Adverse Events by Maximum Toxicity Grade Started During Treatment Phase	Week 1 through Week 6	Toxicity Grading scale 0=none, 1=transient symptom, 2=mild symptom that does not interfere with activities of daily living (ADL's) 3=mild but interfers with ADL's w/o hospitalization. 4=requires hopitalization 5=Death.
Summary of Adverse Events by Maximum Toxicity Grade (Grade 3 or Higher) Started During or After the Chemoradiotherapy Phase	Week 10 through 25	Toxicity Grading scale 0=none, 1= transient symptom, 2=mild symptom that does not interfere with activities of daily living (ADL's) 3=mild but interfers with ADL's w/o hospitalization. 4=requires hopitalization 5=Death.
Comparison of Overall Response During Treatment Phase Using CT/MRI and PET Information	Week 2 - 4	Position Emission Tomography (PET) scans 3-D images are read alongside CT or magnetic resonance imaging (MRI) scans, the combination gives both anatomic and metabolic information. CT = Computerized axial tomography; a type of x-ray for dense areas of the body. MRI = Magnetic Resonance Imaging which captures a picture using Magnets. Better = improvement in response, Worse = response was downgraded.
Comparison of Overall Response During Follow up Phase Using CT/MRI and PET Information	weeks 19 - 25	Position Emission Tomography (PET) scans 3-D images are read alongside CT or magnetic resonance imaging (MRI) scans, the combination gives both anatomic and metabolic information. CT = Computerized axial tomography; a type of x-ray for dense areas of the body. MRI = Magnetic Resonance Imaging which captures a picture using Magnets. Better = improvement in response, Worse = response was downgraded.
Summary of Adverse Events Experienced by 15% or More Subjects in Either Treatment Group	Week 1 through 25	Definition of an adverse event is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Summary of Fatal/Serious Adverse Events During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or After the Chemoradiotherapy Phase. Definition of a serious adverse event is any untoward medicinal occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other.
Summary of Serious Adverse Events During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or After Chemoradiotherapy Phase. Definition of a serious adverse event is any untoward medicinal occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other.
Adverse Events by Maximum Toxicity Grade 3 During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or after Chemoradiotherapy Phase. "Grade 3" are severe and undesirable Adverse Event (significant symptoms requiring hospitalization or invasive intervention; transfusion; elective interventional radiological procedure; therapeutic endoscopy or operation).
Adverse Events (AEs) by Maximum Toxicity Grade 4 During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or after Chemoradiotherapy Phase. "Grade 4" are life-threatening or disabling Adverse Event (complicated by acute, life-threatening metabolic or cardiovascular complications such as circulatory failure, hemorrhage, sepsis. Life-threatening physiologic consequences; need for intensive care or emergent invasive procedure; emergent interventional radiological procedure, therapeutic endoscopy or operation).
Adverse Events by Maximum Toxicity Grade 5 During or After Chemoradiotherapy Phase	Week 10 through 25	Events which started during or after Chemoradiotherapy Phase. "Grade 5" are death related to Adverse Event.
Relative Change From Baseline of Ktrans Median (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an administered contrast agent from -intra into the extravascular tissue over time. Ktrans estimates blood flow and relates to the ease of exchange into extravascular spaces. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g.,tissue perfusion, vessel permeability, vascular surface area, and extracellular/vascular volume fraction) are determined.
Relative Change From Baseline of Ktrans Whole (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an administered contrast agent from -intra into the extravascular tissue over time. Ktrans estimates blood flow and relates to the ease of exchange into extravascular spaces. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g.,tissue perfusion, vessel permeability, vascular surface area, and extracellular/vascular volume fraction) are determined.
Relative Change From Baseline of IAUC Median (90) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.
Relative Change From Baseline of IAUC Mean (90) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.
Relative Change From Baseline of Perfused IAUC (90) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.
Relative Change From Baseline of Whole IAUC(90) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	Dynamic Contrast - enhanced Magnetic Resonance Imaging (DCE-MRI) tracks the diffusion of an intravascularly administered contrast agent from intravascular into the extravascular tissue over time. Initial area under the contrast (IAUC), tracks the concentration versus time curve 90 seconds after contrast injection (IAUC90). By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor microenvironment (e.g., tissue perfusion, vessel permeability, vascular surface area, and extracellular-extra vascular volume fraction) are determined.
Relative Change From Baseline of Kep Median (1/Min) After 2 - 4 Weeks of Treatment	Baseline, and Week 2 - 4	DCE-MRI tracks the diffusion of an intravascularly administered contrast agent into the extravascular tissue over time. Over a period of time, the contrast agent diffuses back into the vasculature (described by the rate constant or Kep). The lower the Kep, the longer the contrast remains in the extravascular space and is more prolonged. A volume transfer (i.e, 1/min) constant of contrast agent is used to determine vascular permeability. By plugging DCE-MRI results into an appropriate pharmacokinetic model, physiological parameters of the tumor (e.g., vessel permeability, etc.) are determined.

Trial Locations

Locations (1)

GSK Investigational Site; 🇪🇸 Madrid, Spain