Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy
- Registration Number
- NCT02780687
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The purpose of this trial is to assess the anti-tumour activity and safety of afatinib monotherapy in patients with urothelial tract carcinoma carrying ERBB2 or ERBB3 (Erythroblastic leukaemia viral oncogene homolog of the human epidermal growth factor family of receptors) mutations or ERBB2 amplifications (Cohort A), and EGFR (Epidermal Growth Factor Receptor) amplification positive tumours (Cohort B), progressing despite previous platinum based chemotherapy, and thereby to improve their prognosis.
The antitumour activity of afatinib monotherapy in these patients will be assessed by progression free survival rate at 6 months (PFS6). This will be the primary endpoint of the trial. A key secondary endpoint will also be defined, the objective response rate (ORR).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Afatinib Afatinib -
- Primary Outcome Measures
Name Time Method Number of Participants With Progression-free Survival at Six Months (PFS6) in Cohort A From start of treatment till assesment at week 24. Progression-free survival at 6 months for Cohort A was defined as the number of patients who were alive and without disease progression at 24-week tumour assessment. Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Baseline imaging was to be performed within 28 days before afatinib treatment start, if the patient already had a tumour assessment within this timeframe, this test was not repeated. Progression is defined as at least a 20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD since the treatment started, together with an absolute increase in the sum of LD of at least 5 millimeter OR The appearance of one or more new lesions.
- Secondary Outcome Measures
Name Time Method Number of Participants With Confirmed Objective Response (ORR) in Cohort A Scans every 8 (±1) weeks from start till end of treatment. Afterwards, if discontinuation was not for progression: every 8 (±1) weeks until month 6, every 12 (±2) weeks thereafter. Until documented disease progression, i.e., up to ~ 20 Months. Confirmed objective response by investigator review for Cohort A was defined as the number of participants with confirmed complete response (CR, disappearance of all target lesions) or confirmed partial response (PR, at least a 30% decrease in sum of longest diameter (LD) of target lesions, reference is baseline sum LD). Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Baseline imaging was to be performed within 28 days before afatinib treatment start, if the patient already had a tumour assessment within this timeframe, this test was not repeated.
Number of Participants With Disease Control (DCR) in Cohort A Scans every 8 (±1) weeks from start till end of treatment. Afterwards, if discontinuation was not for progression: every 8 (±1) weeks until month 6, every 12 (±2) weeks thereafter. Until documented disease progression, i.e., up to ~ 20 Months. Disease control was calculated as the number of participants with complete response (CR, disappearance of all target lesions), partial response (PR, at least a 30% decrease in sum of longest diameter (LD) of target lesions, reference is baseline sum LD), or stable disease (SD, neither sufficient shrinkage to qualify for PR, taking as reference the baseline sum of diameters (SoD), nor sufficient increase to qualify for PD (Progression) taking as reference the smallest SoD since the treatment started). Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Baseline imaging was to be performed within 28 days before afatinib treatment start, if the patient already had a tumour assessment within this timeframe, this test was not repeated.
Number of Patients With Tumour Shrinkage in Cohort A Scans every 8 (±1) weeks from start till end of treatment. Afterwards, if discontinuation was not for progression: every 8 (±1) weeks until month 6, every 12 (±2) weeks thereafter. Until documented disease progression, i.e., up to ~ 20 Months. Number of patients with tumour shrinkage, tumour shrinkage from baseline was defined by the maximum percentage decrease from baseline in the sum of the longest diameters of target lesions. Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Baseline imaging was to be performed within 28 days before afatinib treatment start, if the patient already had a tumour assessment within this timeframe, this test was not repeated.
Progression-free Survival (PFS) in Cohort A Scans every 8 (±1) weeks from start till end of treatment. Afterwards, if discontinuation was not for progression: every 8 (±1) weeks until month 6, every 12 (±2) weeks thereafter. Until documented disease progression, i.e., up to ~ 20 Months. Progression-free survival was defined as the time (months) from the date of the first afatinib administration to the date of disease progression or death (if the patient died without progression). The date of progression for the primary analyses was determined based on investigator assessment. Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to RECIST version 1.1. Baseline imaging was to be performed within 28 days before afatinib treatment start, if the patient already had a tumour assessment within this timeframe, this test was not repeated. Progression is defined as at least a 20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD since the treatment started, together with an absolute increase in the sum of LD of at least 5 millimeter OR The appearance of one or more new lesions.
Overall Survival (OS) in Cohort A From start of treatment of afatinib until death from any cause, i.e. up to approximately 20 Months. Overall survival (OS) defined as the time from start of treatment of afatinib until death from any cause.
Duration of Disease Control in Cohort A Scans every 8 (±1) weeks from start till end of treatment. Afterwards, if discontinuation was not for progression: every 8 (±1) weeks until month 6, every 12 (±2) weeks thereafter. Until documented disease progression, i.e., up to ~ 20 Months. For patients with disease control, duration of disease control was defined as the time from afatinib treatment start to disease progression (or death if the patient died before progression).
Disease control was defined as a having a complete response (CR, disappearance of all target lesions), partial response (PR, at least a 30% decrease in sum of longest diameter (LD) of target lesions, reference is baseline sum LD), or stable disease (SD, neither sufficient shrinkage to qualify for PR, taking as reference the baseline sum of diameters (SoD), nor sufficient increase to qualify for PD taking as reference the smallest SoD since the treatment started). Tumour response was assessed based on local radiological image (CT or MRI) evaluation by the investigators according to RECIST version 1.1. Baseline imaging was to be performed within 28 days before afatinib treatment start, if the patient already had a tumour assessment within this timeframe, this test was not repeated.
Trial Locations
- Locations (30)
A.O. San Camillo Forlanini
🇮🇹Roma, Italy
HOP Foch
🇫🇷Suresnes, France
INS Bergonié
🇫🇷Bordeaux, France
CTR Leon Berard
🇫🇷Lyon, France
INS Cancérologie du Gard
🇫🇷Nîmes, France
HOP Cochin
🇫🇷Paris, France
HOP Saint-Louis
🇫🇷Paris, France
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
HOP Européen G. Pompidou
🇫🇷Paris, France
Ospedale San Donato di Arezzo
🇮🇹Arezzo, Italy
INS Universitaire du Cancer
🇫🇷Toulouse, France
INS Gustave Roussy
🇫🇷Villejuif, France
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari de Girona Doctor Josep Trueta
🇪🇸Girona, Spain
Hospital Universitario de Elche
🇪🇸Elche, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Duran i Reynals
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital Universitario Lucus Augusti
🇪🇸Lugo, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
CIO Clara Campal
🇪🇸Madrid, Spain
Hospital La Paz
🇪🇸Madrid, Spain
Hospital Son Espases
🇪🇸Palma de Mallorca, Spain
CS Parc Taulí
🇪🇸Sabadell, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Hospital Virgen del Rocío
🇪🇸Sevilla, Spain