BIBW 2992 (Afatinib) in Head & Neck Cancer
- Conditions
- Head and Neck NeoplasmsCarcinoma, Squamous Cell
- Interventions
- Registration Number
- NCT00514943
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study is to explore the efficacy of BIBW 2992 compared with cetuximab (Erbitux) in patients with metastatic or recurrent head and neck cancer after failure of platinum-containing therapy. In addition, the trial aims to clarify the influence of EGFR genotype on tumor response to the treatment regimens.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 124
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description BIBW 2992 BIBW 2992 once daily taken orally Cetuximab Cetuximab once every week by intravenous injection
- Primary Outcome Measures
Name Time Method Tumor Shrinkage Before Crossover (Stage 1) of the Trial as Per Investigator Assessment From randomization until start of Stage 2 treatment, or within 28 days after the termination of Stage 1. Tumor shrinkage before crossover was defined as the change from baseline in the smallest post-randomisation sum of the longest diameters of target lesions (SLD), calculated as the smallest SLD after randomisation but before crossover minus SLD at baseline. Baseline was the SLD measured before randomisation. A negative value means the smallest post-randomisation SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline.
Mean calculated is actually the Adjusted mean. Adjusted mean is obtained from fitting an ANCOVA model including treatment, stratification factor prior chemotherapy for recurrent/metastatic disease and the baseline sum of longest distance of target lesions as covariates.
- Secondary Outcome Measures
Name Time Method Tumor Shrinkage After Crossover (Stage 2) as Per Investigator Assessments From baseline assessed prior to first dose of Stage 2 study medication to 28 days after termination of Stage 2 treatment. Tumor shrinkage after crossover was defined as the change from baseline in the smallest post-crossover sum of the longest diameters of target lesions (SLD), calculated as the smallest SLD after crossover minus SLD at baseline. Baseline was the SLD measured at the time of crossover, or the closest measurement before the patient started stage 2 treatment. A negative value means the smallest post-crossover SLD was smaller than baseline (decreased after crossover), a positive value means tumor size increased after crossover.
Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment). Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment Best RECIST Assessment is defined as confirmed Disease control (complete response (CR), partial response (PR) and Stable disease (SD)), Objective response ( complete response (CR) or partial response (PR)) assessed by the investigator according to the RECIST 1.0 criteria.
Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment). Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment Best RECIST Assessment is defined as confirmed Disease control (complete response (CR), partial response (PR) and Stable disease (SD)), Best objective response ( complete response (CR) or partial response (PR)) as assessed by the independent central review (ICR) according to the RECIST 1.0 criteria.
Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment) Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment Best RECIST Assessment is defined as confirmed Disease control (complete response (CR), partial response (PR) and Stable disease (SD)), Objective response ( complete response (CR) or partial response (PR)) assessed by the investigator according to the RECIST 1.0 criteria.
Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment) Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment Best RECIST Assessment is defined as confirmed Disease control (complete response (CR), partial response (PR) and Stable disease (SD)), Best objective response ( complete response (CR) or partial response (PR)) as assessed by the independent central review (ICR) according to the RECIST 1.0 criteria.
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 1 Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment Best RECIST Assessment as onset of confirmed objective response as per Investigator assessment for Stage 1.
Best RECIST Assessment as Onset of Confirmed Objective Response as as Per ICR for Stage 1 Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment Best RECIST Assessment as onset of confirmed objective response as per the independent central review (ICR) according to the RECIST 1.0 criteria.
Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 2 Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment Best RECIST Assessment as onset of confirmed objective response as per Investigator assessment according to the RECIST 1.0 criteria.
Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 1 Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment Best RECIST Assessment as duration of confirmed objective response and disease control as per Investigator assessment according to the RECIST 1.0 criteria.
Best RECIST Assessment as Confirmed Duration of Confirmed Objective Response and Disease Control as Per ICR for Stage 1 Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment Best RECIST Assessment as duration of confirmed objective response and disease control as per the independent central review (ICR) according to the RECIST 1.0 criteria.
Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 2 Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment Best RECIST Assessment as confirmed duration of objective response and disease control as per Investigator assessment according to the RECIST 1.0 criteria.
Best RECIST Assessment as Confirmed Duration of Disease Control as Per ICR for Stage 2 Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment Best RECIST Assessment as confirmed duration of disease control as per the independent central review (ICR) assessment according to the RECIST 1.0 criteria.
Progression Free Survival (PFS) Before Crossover Based on Investigator Assessment From randomisation to disease progression in Stage 1 or death whichever occurred first before crossover. PFS is defined as time from randomisation to until the occurrence of tumor progression or death, whichever occurred first, during Stage 1 of the trial.
Median is calculated from the Kaplan-Meier curve for each treatment group.Progression Free Survival (PFS) After Crossover Based on Investigator Assessment From first administration of study medication after cross over to disease progression in Stage 2 or death whichever came first after crossover. PFS is defined as time from first administration study medication after cross over until the occurrence of tumor progression or death, whichever came first, during Stage 2 of the trial.
Median is calculated from the Kaplan-Meier curve for each treatment group.Overall Survival (OS) From randomisation to data cut-off date. OS is defined as time from randomisation to death.
Median is calculated from the Kaplan-Meier curve for each treatment group.Time to Deterioration in HRQoL - Stage 1 From randomisation to deterioration in HRQoL scores before crossover. Health related Quality of Life (HRQoL) for Time to deterioration was assessed using the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Head and Neck Cancer Module (H\&N35).
Time to deterioration in HRQoL (defined as a 10-point change towards worsening from the baseline score on a 0-100 point scale) was determined for:
* global health status (Questions 29 and 30 in EORTC QLQ C30)
* pain (Questions 9 and 19 in EORTC QLQ C30)
* swallowing (Questions 35 to 38 in EORTC QLQ-H\&N35)Patients With AEs Resulting in Diarrhea, Skin Rash, Dose Reduction, Treatment Discontinuation and Decreased Cardiac Left Ventricular Function First administration of trial medication until 28 days after last drug administration Patients with adverse events (AEs) resulting in Diarrhea, Skin Rash, dose reduction, treatment discontinuation and decreased cardiac left ventricular function
Note: To asses the Decreased Cardiac left ventricular function, Left ventricular ejection fraction (LVEF) was assessed in patients treated with afatinib in Stage 1 and Stage 2 . And no patients in either group had a significant change in LVEF during Stage 1 or Stage 2 of the trial.Incidence and Intensity of Adverse Events With Grading According CTCAE First administration of trial medication until 28 days after last drug administration Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).
Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 15 (Cpre,ss,15) Day 15 Cpre,ss,15 represents the pre-dose concentration of afatinib in plasma at steady state on day 15.
Note: At day 15, values for afatinib 40 mg no values reported in stage 1 and stage 2.Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 29 (Cpre,ss,29) Day 29 Cpre,ss,29 represents the pre-dose concentration of afatinib in plasma at steady state on day 29.
Note: At day 29, values for afatinib 40 mg no values reported in stage 2.Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 57 (Cpre,ss, 57) Day 57 Cpre,ss,57 represents the pre-dose concentration of afatinib in plasma at steady state on day 57.
Trial Locations
- Locations (36)
1200.28.0024 Boehringer Ingelheim Investigational Site
🇺🇸Baltimore, Maryland, United States
1200.28.0001 Boehringer Ingelheim Investigational Site
🇺🇸Chicago, Illinois, United States
1200.28.0010 Boehringer Ingelheim Investigational Site
🇺🇸Stanford, California, United States
1200.28.0030 Boehringer Ingelheim Investigational Site
🇧🇪Bruxelles, Belgium
1200.28.0020 Boehringer Ingelheim Investigational Site
🇺🇸Milwaukee, Wisconsin, United States
1200.28.0050A Boehringer Ingelheim Investigational Site
🇫🇷Montpellier cedex 5, France
1200.28.0055G Boehringer Ingelheim Investigational Site
🇫🇷Rouen, France
1200.28.0044 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1200.28.0040 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1200.28.0052A Boehringer Ingelheim Investigational Site
🇫🇷Lille, France
1200.28.0022 Boehringer Ingelheim Investigational Site
🇺🇸Indianapolis, Indiana, United States
1200.28.0004 Boehringer Ingelheim Investigational Site
🇺🇸Winston-Salem, North Carolina, United States
1200.28.0059A Boehringer Ingelheim Investigational Site
🇫🇷Avignon, France
1200.28.0051A Boehringer Ingelheim Investigational Site
🇫🇷Lyon, France
1200.28.0032 Boehringer Ingelheim Investigational Site
🇧🇪Leuven, Belgium
1200.28.0006 Boehringer Ingelheim Investigational Site
🇺🇸Omaha, Nebraska, United States
1200.28.0012 Boehringer Ingelheim Investigational Site
🇺🇸Ann Arbor, Michigan, United States
1200.28.0002 Boehringer Ingelheim Investigational Site
🇺🇸Jackson, Mississippi, United States
1200.28.0058A Boehringer Ingelheim Investigational Site
🇫🇷Nimes cedex 9, France
1200.28.0062A Boehringer Ingelheim Investigational Site
🇫🇷Ales, France
1200.28.0062B Boehringer Ingelheim Investigational Site
🇫🇷Ales, France
1200.28.0011 Boehringer Ingelheim Investigational Site
🇺🇸Harvey, Illinois, United States
1200.28.0008 Boehringer Ingelheim Investigational Site
🇺🇸New Hyde Park, New York, United States
1200.28.0005 Boehringer Ingelheim Investigational Site
🇺🇸Chicago, Illinois, United States
1200.28.0031 Boehringer Ingelheim Investigational Site
🇧🇪Gent, Belgium
1200.28.0007 Boehringer Ingelheim Investigational Site
🇺🇸Houston, Texas, United States
1200.28.0016 Boehringer Ingelheim Investigational Site
🇺🇸Rochester, Minnesota, United States
1200.28.0021 Boehringer Ingelheim Investigational Site
🇺🇸St. Joseph, Michigan, United States
1200.28.0061A Boehringer Ingelheim Investigational Site
🇫🇷Poitiers, France
1200.28.0043 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1200.28.0045 Boehringer Ingelheim Investigational Site
🇪🇸Santander, Spain
1200.28.0042 Boehringer Ingelheim Investigational Site
🇪🇸Malaga, Spain
1200.28.0041 Boehringer Ingelheim Investigational Site
🇪🇸Valencia, Spain
1200.28.0009 Boehringer Ingelheim Investigational Site
🇺🇸Madison, Wisconsin, United States
1200.28.0017 Boehringer Ingelheim Investigational Site
🇺🇸Chapel Hill, North Carolina, United States
1200.28.0013 Boehringer Ingelheim Investigational Site
🇺🇸Charleston, South Carolina, United States