Urologic NeoplasmsPhase 2LUX-Bladder 1NCT02780687
Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy
A Phase 2 study testing Afatinib in people with Urologic Neoplasms, run by Boehringer Ingelheim at 30 sites in 3 countries.
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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urologic Neoplasms
- What is being tested?
- Afatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 30 sitesin 3 countries
- Study dates
- 9 Jun 2016to 2 Sep 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
30 sites in 3 countries.
30 sites in 3 countries
Spain19 sites
Hospital Germans Trias i Pujol
Badalona, 08916
Hospital del Mar
Barcelona, 08003
Hospital Santa Creu i Sant Pau
Barcelona, 08025
Hospital Clínic de Barcelona
Barcelona, 08036
Hospital Vall d'Hebron
Barcelona, 08038
Hospital Universitario de Elche
Elche, 03202
Hospital Universitari de Girona Doctor Josep Trueta
Girona, 17007
Hospital Duran i Reynals
L'Hospitalet de Llobregat, 08908
Hospital Universitario Lucus Augusti
Lugo, 27003
Hospital Ramón y Cajal
Madrid, 28034
Hospital Clínico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital La Paz
Madrid, 28046
CIO Clara Campal
Madrid, 28050
Hospital Son Espases
Palma de Mallorca, 07010
CS Parc Taulí
Sabadell, 08208
Hospital Virgen Macarena
Seville, 41009
Hospital Virgen del Rocío
Seville, 41013
Instituto Valenciano de Oncología
Valencia, 46009
France9 sites
INS Bergonié
Bordeaux, 33076
CTR Leon Berard
Lyon, 69373
INS Cancérologie du Gard
Nîmes, 30029
HOP Saint-Louis
Paris, 75010
HOP Cochin
Paris, 75014
HOP Européen G. Pompidou
Paris, 75015
HOP Foch
Suresnes, 92150
INS Universitaire du Cancer
Toulouse, 31059
INS Gustave Roussy
Villejuif, 94805
Italy2 sites
Ospedale San Donato di Arezzo
Arezzo, 52100
A.O. San Camillo Forlanini
Roma, 00152
About this study
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.
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).
- Conditions
- Urologic Neoplasms
- Being tested
- Afatinib
- Medical subject headings
- Urologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
| Study group | Role | What they receive |
|---|---|---|
| Afatinib | Experimental | Not described Receives: Drug: Afatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From start of treatment till assesment at week 24.
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2016 (estimated)
- Study start9 Jun 2016
- Primary completion24 Sep 2018
- Study completion2 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Urologic NeoplasmsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02780687
- Sponsor's protocol ID
- 1200.261
- Other IDs
- 2015-005427-10, 2015
- Acronym
- LUX-Bladder 1
- Status last verified
- Oct 2020
- First submitted
- 20 May 2016
- Last updated
- 18 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Font A, Mellado B, Climent MA, Virizuela JA, Oudard S, Puente J, Castellano D, Gonzalez-Del-Alba A, Pinto A, Morales-Barrera R, Rodriguez-Vida A, Fernandez PL, Teixido C, Jares P, Aldecoa I, Gibson N, Solca F, Mondal S, Lorence RM, Serra J, Real FX. Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1). Br J Cancer. 2024 Feb;130(3):434-441. doi: 10.1038/s41416-023-02513-6. Epub 2023 Dec 15.
PubMed 38102226
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02780687
- Acronym / sponsor ID
- LUX-Bladder 1 / 1200.261
- Conditions
- Urologic Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 9 Jun 2016 (actual)
- Primary completion
- 24 Sep 2018 (actual)
- Study completion
- 2 Sep 2019 (actual)
- First posted
- 23 May 2016 (estimated)
- Results
- Posted 12 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Afatinib | Experimental | Drug: Afatinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Afatinib | Drug | Afatinib |
Primary outcome
Number of Participants With Progression-free Survival at Six Months (PFS6) in Cohort A
Time frame: 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.
6 secondary outcomes
Number of Participants With Confirmed Objective Response (ORR) in Cohort A
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.
Progression-free Survival (PFS) in Cohort A
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.
Overall Survival (OS) in Cohort A
Time frame: 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
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.
Duration of Disease Control in Cohort A
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.
Number of Patients With Tumour Shrinkage in Cohort A
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38102226Font A, Mellado B, Climent MA, Virizuela JA, Oudard S, Puente J, Castellano D, Gonzalez-Del-Alba A, Pinto A, Morales-Barrera R, Rodriguez-Vida A, Fernandez PL, Teixido C, Jares P, Aldecoa I, Gibson N, Solca F, Mondal S, Lorence RM, Serra J, Real FX. Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1). Br J Cancer. 2024 Feb;130(3):434-441. doi: 10.1038/s41416-023-02513-6. Epub 2023 Dec 15.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
30 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Afatinib in people with Urologic Neoplasms, run by Boehringer Ingelheim at 30 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Spain, France, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Progression-free Survival at Six Months (PFS6) in Cohort A (time frame: From start of treatment till assesment at week 24.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02780687, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2020; AzTrials last refreshed its copy on 8 Nov 2026.