Have you or your loved ones been diagnosed with urologic neoplasms?

You may be eligible to participate in a urologic neoplasms clinical trial.

Have you or your loved ones been diagnosed with urologic neoplasms? You may be eligible to participate in a urologic neoplasms clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Urologic Neoplasms Clinical Trial in L'Hospitalet de Llobregat

NCT02780687 | Phase 2 | Interventional

Have you or your loved ones been diagnosed with urologic neoplasms?

You may be eligible to participate in a urologic neoplasms clinical trial.

Have you or your loved ones been diagnosed with urologic neoplasms? You may be eligible to participate in a urologic neoplasms clinical trial.

Completed

Male & Female

18 Years +

This study has recruited 42 Participants

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).

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Details for the study

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).

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

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.

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.

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.

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.

Study 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