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

• ClinicalTrials.gov Identifier: NCT02780687
• Recruitment Status: Completed
• First Posted: May 23, 2016
• Results First Posted: October 12, 2020
• Last Update Posted: November 18, 2020
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: May 20, 2016
• First Posted Date: May 23, 2016
• Results First Submitted Date: September 17, 2020
• Results First Posted Date: October 12, 2020
• Last Update Posted Date: November 18, 2020
• Actual Study Start Date: June 9, 2016
• Actual Primary Completion Date: September 24, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 28, 2020)

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.

• Original Primary Outcome Measures (submitted: May 20, 2016): Progression Free Survival at 6 months in Cohort A (defined as the proportion of patients who does not show disease progression by the 24-week tumour assessment). [ Time Frame: 24 weeks ]

Current Secondary Outcome Measures (submitted: October 28, 2020)

• 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. ]
  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 [ 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 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 [ Time Frame: 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.
• 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. ]
  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 [ 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. ]
  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 [ 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, 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.

Original Secondary Outcome Measures (submitted: May 20, 2016)

• Objective response rate (ORR) in Cohort A, defined as number of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. [ Time Frame: From Baseline to disease progression (up to 2 years) ]
• Progression free survival (PFS) in Cohort A, defined as the time from first drug administration to the date of disease progression, or date of death whichever is earlier [ Time Frame: Starting with first drug administration and until up to 2 years for each patient ]
• Overall Survival (OS) in Cohort A, defined as the time from first drug administration to the date of death [ Time Frame: From first drug administration to date of death (up to 5 years) ]
• Disease Control Rate (DCR) in Cohort A, defined as complete response (CR), partial response (PR), stable disease (SD) or Non-CR/Non-Progressive Disease (NN) according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1 [ Time Frame: From first drug administration to disease progression (up to 2 years) ]
• Duration of objective response (DOR) in Cohort A, according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1 [ Time Frame: From first drug administration to disease progression (up to 2 years) ]
• Tumour shrinkage in Cohort A, measured as the maximum percentage decrease from baseline sum of target lesion diameters after treatment until disease progression [ Time Frame: From first drug administration to disease progression (up to 2 years) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy
• 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.

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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urologic Neoplasms
• Intervention: Drug: Afatinib

Study Arms

Experimental: Afatinib

Intervention: Drug: Afatinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 17, 2020): 42
• Original Estimated Enrollment (submitted: May 20, 2016): 80
• Actual Study Completion Date: September 2, 2019
• Actual Primary Completion Date: September 24, 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Italy, Spain

Administrative Information

• NCT Number: NCT02780687
• Other Study ID Numbers: 1200.261; 2015-005427-10 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: Boehringer Ingelheim
• Verification Date: October 2020