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

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.

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).

Study Overview

• Status: Completed
• Conditions: Urologic Neoplasms
• Intervention / Treatment: Drug: Afatinib

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • INS Bergonie
  • Lyon, France, 69373
    • CTR Leon Berard
  • Nîmes, France, 30029
    • INS Cancérologie du Gard
  • Paris, France, 75010
    • HOP Saint-Louis
  • Paris, France, 75014
    • HOP Cochin
  • Paris, France, 75015
    • HOP Européen G. Pompidou
  • Suresnes, France, 92150
    • HOP Foch
  • Toulouse, France, 31059
    • INS Universitaire du Cancer
  • Villejuif, France, 94805
    • INS Gustave Roussy
• Italy
  • Arezzo, Italy, 52100
    • Ospedale San Donato di Arezzo
  • Roma, Italy, 00152
    • A.O. San Camillo Forlanini
• Spain
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08025
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain, 08038
    • Hospital Vall d'Hebron
  • Elche, Spain, 03202
    • Hospital universitario de Elche
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Doctor Josep Trueta
  • L'Hospitalet de Llobregat, Spain, 08908
    • Hospital Duran I Reynals
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain, 28050
    • CIO Clara Campal
  • Palma de Mallorca, Spain, 07010
    • Hospital Son Espases
  • Sabadell, Spain, 08208
    • CS Parc Taulí
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío
  • Sevilla, Spain, 41009
    • Hospital Virgen Macarena
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncología

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afatinib	Drug: Afatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From start of treatment till assesment at week 24.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 (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.	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.
Overall Survival (OS) in Cohort A	Overall survival (OS) defined as the time from start of treatment of afatinib until death from any cause.	From start of treatment of afatinib until death from any cause, i.e. up to approximately 20 Months.
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.	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.
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.	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 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.	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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2016
• Primary Completion (Actual): September 24, 2018
• Study Completion (Actual): September 2, 2019

Study Registration Dates

• First Submitted: May 20, 2016
• First Submitted That Met QC Criteria: May 20, 2016
• First Posted (Estimate): May 23, 2016

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: 1200.261; 2015-005427-10 (EudraCT Number)