Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy (LUX-Bladder 1)
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| ClinicalTrials.gov Identifier: NCT02780687 |
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Recruitment Status :
Completed
First Posted : May 23, 2016
Results First Posted : October 12, 2020
Last Update Posted : November 18, 2020
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Sponsor:
Boehringer Ingelheim
Information provided by (Responsible Party):
Boehringer Ingelheim
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Urologic Neoplasms | Drug: Afatinib | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 42 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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. |
| Actual Study Start Date : | June 9, 2016 |
| Actual Primary Completion Date : | September 24, 2018 |
| Actual Study Completion Date : | September 2, 2019 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
| Experimental: Afatinib |
Drug: Afatinib |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02780687
Locations
Show 30 study locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
| Study Chair: | Boehringer Ingelheim | Boehringer Ingelheim |
Study Documents (Full-Text)
Documents provided by Boehringer Ingelheim:
Documents provided by Boehringer Ingelheim:
Study Protocol [PDF] March 13, 2017
Statistical Analysis Plan [PDF] October 1, 2018
Additional Information:
| Responsible Party: | Boehringer Ingelheim |
| ClinicalTrials.gov Identifier: | NCT02780687 |
| Other Study ID Numbers: |
1200.261 2015-005427-10 ( EudraCT Number ) |
| First Posted: | May 23, 2016 Key Record Dates |
| Results First Posted: | October 12, 2020 |
| Last Update Posted: | November 18, 2020 |
| Last Verified: | October 2020 |
Additional relevant MeSH terms:
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Urologic Neoplasms Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Male Urogenital Diseases |
Urologic Diseases Afatinib Tyrosine Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |