Clinical trial NCT02780687: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urologic Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-05-23
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Number of Participants With Progression-free Survival at Six Months (PFS6) in Cohort A
timeFrame: From start of treatment till assesment at week 24.
Secondary outcomes:
measure: Number of Participants With Confirmed Objective Response (ORR) in Cohort A
timeFrame: 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.
measure: Progression-free Survival (PFS) in Cohort A
timeFrame: 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.
measure: Overall Survival (OS) in Cohort A
timeFrame: From start of treatment of afatinib until death from any cause, i.e. up to approximately 20 Months.
measure: Number of Participants With Disease Control (DCR) in Cohort A
timeFrame: 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.
measure: Duration of Disease Control in Cohort A
timeFrame: 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.
measure: Number of Patients With Tumour Shrinkage in Cohort A
timeFrame: 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.
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: INS Bergonié
city: Lyon
country: France
facility: CTR Leon Berard
city: Nîmes
country: France
facility: INS Cancérologie du Gard
city: Paris
country: France
facility: HOP Saint-Louis
city: Paris
country: France
facility: HOP Cochin
city: Paris
country: France
facility: HOP Européen G. Pompidou
city: Suresnes
country: France
facility: HOP Foch
city: Toulouse
country: France
facility: INS Universitaire du Cancer
city: Villejuif
country: France
facility: INS Gustave Roussy
city: Arezzo
country: Italy
facility: Ospedale San Donato di Arezzo
city: Roma
country: Italy
facility: A.O. San Camillo Forlanini
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Elche
country: Spain
facility: Hospital Universitario de Elche
city: Girona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Duran i Reynals
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: CIO Clara Campal
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
city: Sabadell
country: Spain
facility: CS Parc Taulí
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: