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.


Condition: Urologic Neoplasms

Intervention:

  • Drug: Afatinib

Purpose: 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 mutations or ERBB2 amplifications (Cohort A), and EGFR 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 Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02780687

Sponsor: Boehringer Ingelheim

Primary Outcome Measures:

  • Measure: 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
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: 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)
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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)
  • Safety Issue:
  • Measure: 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)
  • Safety Issue:
  • Measure: 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)
  • Safety Issue:
  • Measure: 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)
  • Safety Issue:

Estimated Enrollment: 80

Study Start Date: June 9, 2016

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

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:

  • 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

Contact:

  • Boehringer Ingelheim Call Center
  • 1-800-243-0127

Locations:

  • INS Bergonié
  • Bordeaux 33076 France
  • CTR Léon Bérard
  • Lyon 69373 France
  • INS Cancérologie du Gard
  • Nîmes 30029 France
  • HOP Saint-Louis
  • Paris 75010 France
  • HOP Cochin
  • Paris 75014 France
  • HOP Européen G. Pompidou
  • Paris 75015 France
  • HOP Foch
  • Suresnes 92150 France
  • INS Claudius Regaud
  • Toulouse 31059 France
  • INS Gustave Roussy
  • Villejuif 94805 France
  • Ospedale San Donato di Arezzo
  • Arezzo 52100 Italy
  • A.O. San Camillo Forlanini
  • Roma 00152 Italy
  • Hospital Germans Trias i Pujol
  • Badalona 08916 Spain
  • Hospital del Mar
  • Barcelona 08003 Spain
  • Hospital Santa Creu i Sant Pau
  • Barcelona 08025 Spain
  • Hospital Clínic de Barcelona
  • Barcelona 08036 Spain
  • Hospital Vall d'Hebron
  • Barcelona 08038 Spain
  • Hospital Universitario de Elche
  • Elche 03202 Spain
  • Hospital Universitari de Girona Doctor Josep Trueta
  • Girona 17007 Spain
  • Hospital Duran i Reynals
  • L'Hospitalet de Llobregat 08908 Spain
  • Hospital Universitario Lucus Augusti
  • Lugo 27003 Spain
  • Hospital Ramón y Cajal
  • Madrid 28034 Spain
  • Hospital Clínico San Carlos
  • Madrid 28040 Spain
  • Hospital Universitario 12 de Octubre
  • Madrid 28041 Spain
  • Hospital La Paz
  • Madrid 28046 Spain
  • CIO Clara Campal
  • Madrid 28050 Spain
  • Hospital Son Espases
  • Palma de Mallorca 07010 Spain
  • CS Parc Taulí
  • Sabadell 08208 Spain
  • Hospital Virgen Macarena
  • Sevilla 41009 Spain
  • Hospital Virgen del Rocío
  • Sevilla 41013 Spain
  • Instituto Valenciano de Oncología
  • Valencia 46009 Spain

View trial on ClinicalTrials.gov


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