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

Urologic Neoplasms Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02780687
• Other study ID #: 1200.261
• Secondary ID: 2015-005427-10
• Status: Completed
• Phase: Phase 2
• Start date: June 9, 2016
• Est. completion date: September 2, 2019

Study information

• Verified date: October 2020
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 2, 2019
• Est. primary completion date: September 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Urologic Neoplasms

Intervention

Drug:
• Afatinib

Locations

Country	Name	City	State
France	INS Bergonié	Bordeaux
France	CTR Leon Berard	Lyon
France	INS Cancérologie du Gard	Nîmes
France	HOP Cochin	Paris
France	HOP Européen G. Pompidou	Paris
France	HOP Saint-Louis	Paris
France	HOP Foch	Suresnes
France	INS Universitaire du Cancer	Toulouse
France	INS Gustave Roussy	Villejuif
Italy	Ospedale San Donato di Arezzo	Arezzo
Italy	A.O. San Camillo Forlanini	Roma
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Elche	Elche
Spain	Hospital Universitari de Girona Doctor Josep Trueta	Girona
Spain	Hospital Duran i Reynals	L'Hospitalet de Llobregat
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	CIO Clara Campal	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Son Espases	Palma de Mallorca
Spain	CS Parc Taulí	Sabadell
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Virgen Macarena	Sevilla
Spain	Instituto Valenciano de Oncología	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

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