Lapatinib Versus Placebo Given Concurrently With Cisplatin And Radiotherapy In Patients With Unresected Head And Neck Cancer
- Conditions
- Neoplasms, Head and Neck
- Interventions
- Registration Number
- NCT00387127
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 67
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Lapatinib oral tablets orally daily Lapatinib Lapatinib oral tablets 1500mg lapatinib orally daily Lapatinib radiotherapy 1500mg lapatinib orally daily Lapatinib cisplatin chemotherapy 1500mg lapatinib orally daily Placebo radiotherapy orally daily Placebo cisplatin chemotherapy orally daily
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 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.
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.
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 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.
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.
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.
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).
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.
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.
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).
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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Sheffield, United Kingdom