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Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy (LUX-Bladder 1)

Primary Purpose

Urologic Neoplasms

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Afatinib
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urologic Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Recurrent or metastatic urothelial cancer
  • Patients must have failed prior platinum based treatment (adjuvant or 1st line)
  • Archival tissue sample available for biomarker testing at pre-screening and tissue banking.
  • Patients should complete a pre-screening biomarker analysis and should fulfill the following: for Cohort A tumour should show a ERBB2 (epidermal growth factor family receptor 2) or ERBB3 mutation, or ERBB2 gene amplification; for Cohort B tumour should show EGFR (Epidermal Growth Factor Receptor) amplification.
  • Further inclusion criteria apply

Exclusion criteria:

  • Prior use of EGFR, ERBB2 or ERBB3 targeted treatment
  • Chemotherapy within 4 weeks prior to the start of study treatment. Biological therapy or investigational agents within 4 weeks prior to the start of study treatment or prior to passing 5 half-lives, i.e. systemic clearance, whatever comes first
  • Known brain metastases or signs hereof, uncontrolled spinal cord compression or leptomeningeal carcinomatosis
  • Further exclusion criteria apply

Sites / Locations

  • INS Bergonié
  • CTR Leon Berard
  • INS Cancérologie du Gard
  • HOP Saint-Louis
  • HOP Cochin
  • HOP Européen G. Pompidou
  • HOP Foch
  • INS Universitaire du Cancer
  • INS Gustave Roussy
  • Ospedale San Donato di Arezzo
  • A.O. San Camillo Forlanini
  • Hospital Germans Trias i Pujol
  • Hospital del Mar
  • Hospital Santa Creu i Sant Pau
  • Hospital Clínic de Barcelona
  • Hospital Vall d'Hebron
  • Hospital Universitario de Elche
  • Hospital Universitari de Girona Doctor Josep Trueta
  • Hospital Duran i Reynals
  • Hospital Universitario Lucus Augusti
  • Hospital Ramón y Cajal
  • Hospital Clínico San Carlos
  • Hospital Universitario 12 de Octubre
  • Hospital La Paz
  • CIO Clara Campal
  • Hospital Son Espases
  • CS Parc Taulí
  • Hospital Virgen Macarena
  • Hospital Virgen del Rocío
  • Instituto Valenciano de Oncología

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Afatinib

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Progression-free Survival at Six Months (PFS6) in Cohort A
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

Number of Participants With Confirmed Objective Response (ORR) in Cohort A
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.
Progression-free Survival (PFS) in Cohort A
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
Overall survival (OS) defined as the time from start of treatment of afatinib until death from any cause.
Number of Participants With Disease Control (DCR) in Cohort A
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.
Duration of Disease Control in Cohort A
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.
Number of Patients With Tumour Shrinkage in Cohort A
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.

Full Information

First Posted
May 20, 2016
Last Updated
October 28, 2020
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT02780687
Brief Title
Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy
Acronym
LUX-Bladder 1
Official Title
LUX-Bladder 1: Phase II Open Label Single Arm Exploratory Trial of Oral Afatinib Monotherapy Following Platinum Failure for Patients With Advanced/Metastatic Urothelial Tract Carcinoma With Genetic Alterations in ERBB Receptors.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
June 9, 2016 (Actual)
Primary Completion Date
September 24, 2018 (Actual)
Study Completion Date
September 2, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urologic Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Afatinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Afatinib
Primary Outcome Measure Information:
Title
Number of Participants With Progression-free Survival at Six Months (PFS6) in Cohort A
Description
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.
Time Frame
From start of treatment till assesment at week 24.
Secondary Outcome Measure Information:
Title
Number of Participants With Confirmed Objective Response (ORR) in Cohort A
Description
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.
Time Frame
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.
Title
Progression-free Survival (PFS) in Cohort A
Description
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.
Time Frame
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.
Title
Overall Survival (OS) in Cohort A
Description
Overall survival (OS) defined as the time from start of treatment of afatinib until death from any cause.
Time Frame
From start of treatment of afatinib until death from any cause, i.e. up to approximately 20 Months.
Title
Number of Participants With Disease Control (DCR) in Cohort A
Description
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.
Time Frame
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.
Title
Duration of Disease Control in Cohort A
Description
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.
Time Frame
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.
Title
Number of Patients With Tumour Shrinkage in Cohort A
Description
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.
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Recurrent or metastatic urothelial cancer Patients must have failed prior platinum based treatment (adjuvant or 1st line) Archival tissue sample available for biomarker testing at pre-screening and tissue banking. Patients should complete a pre-screening biomarker analysis and should fulfill the following: for Cohort A tumour should show a ERBB2 (epidermal growth factor family receptor 2) or ERBB3 mutation, or ERBB2 gene amplification; for Cohort B tumour should show EGFR (Epidermal Growth Factor Receptor) amplification. Further inclusion criteria apply Exclusion criteria: Prior use of EGFR, ERBB2 or ERBB3 targeted treatment Chemotherapy within 4 weeks prior to the start of study treatment. Biological therapy or investigational agents within 4 weeks prior to the start of study treatment or prior to passing 5 half-lives, i.e. systemic clearance, whatever comes first Known brain metastases or signs hereof, uncontrolled spinal cord compression or leptomeningeal carcinomatosis Further exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
INS Bergonié
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CTR Leon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
INS Cancérologie du Gard
City
Nîmes
ZIP/Postal Code
30029
Country
France
Facility Name
HOP Saint-Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
HOP Cochin
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
HOP Européen G. Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
HOP Foch
City
Suresnes
ZIP/Postal Code
92150
Country
France
Facility Name
INS Universitaire du Cancer
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
INS Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Ospedale San Donato di Arezzo
City
Arezzo
ZIP/Postal Code
52100
Country
Italy
Facility Name
A.O. San Camillo Forlanini
City
Roma
ZIP/Postal Code
00152
Country
Italy
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08038
Country
Spain
Facility Name
Hospital Universitario de Elche
City
Elche
ZIP/Postal Code
03202
Country
Spain
Facility Name
Hospital Universitari de Girona Doctor Josep Trueta
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
Hospital Duran i Reynals
City
L'Hospitalet de Llobregat
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hospital Universitario Lucus Augusti
City
Lugo
ZIP/Postal Code
27003
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
CIO Clara Campal
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Son Espases
City
Palma de Mallorca
ZIP/Postal Code
07010
Country
Spain
Facility Name
CS Parc Taulí
City
Sabadell
ZIP/Postal Code
08208
Country
Spain
Facility Name
Hospital Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Hospital Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Instituto Valenciano de Oncología
City
Valencia
ZIP/Postal Code
46009
Country
Spain

12. IPD Sharing Statement

Links:
URL
https://trials.boehringer-ingelheim.com/
Description
Related Info

Learn more about this trial

Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy

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