NCT02780687

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2016

Typical duration for phase_2

Geographic Reach
3 countries

30 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 20, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 23, 2016

Completed
17 days until next milestone

Study Start

First participant enrolled

June 9, 2016

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 24, 2018

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 2, 2019

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

October 12, 2020

Completed
Last Updated

November 18, 2020

Status Verified

October 1, 2020

Enrollment Period

2.3 years

First QC Date

May 20, 2016

Results QC Date

September 17, 2020

Last Update Submit

October 28, 2020

Conditions

Urologic Neoplasms

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • Number of Participants With Confirmed Objective Response (ORR) in Cohort A

    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 (PFS) in Cohort A

    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.

  • Overall Survival (OS) in Cohort A

    From start of treatment of afatinib until death from any cause, i.e. up to approximately 20 Months.

  • Number of Participants With Disease Control (DCR) in Cohort A

    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.

  • Duration of Disease Control in Cohort A

    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.

  • +1 more secondary outcomes

Study Arms (1)

Afatinib

EXPERIMENTAL
Drug: Afatinib

Interventions

AfatinibDRUG
Afatinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

INS Bergonié

Bordeaux, 33076, France

Location

CTR Leon Berard

Lyon, 69373, France

Location

INS Cancérologie du Gard

Nîmes, 30029, France

Location

HOP Saint-Louis

Paris, 75010, France

Location

HOP Cochin

Paris, 75014, France

Location

HOP Européen G. Pompidou

Paris, 75015, France

Location

HOP Foch

Suresnes, 92150, France

Location

INS Universitaire du Cancer

Toulouse, 31059, France

Location

INS Gustave Roussy

Villejuif, 94805, France

Location

Ospedale San Donato di Arezzo

Arezzo, 52100, Italy

Location

A.O. San Camillo Forlanini

Roma, 00152, Italy

Location

Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08038, Spain

Location

Hospital Universitario de Elche

Elche, 03202, Spain

Location

Hospital Universitari de Girona Doctor Josep Trueta

Girona, 17007, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital La Paz

Madrid, 28046, Spain

Location

CIO Clara Campal

Madrid, 28050, Spain

Location

Hospital Son Espases

Palma de Mallorca, 07010, Spain

Location

CS Parc Taulí

Sabadell, 08208, Spain

Location

Hospital Virgen Macarena

Seville, 41009, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Related Publications (1)

  • Font A, Mellado B, Climent MA, Virizuela JA, Oudard S, Puente J, Castellano D, Gonzalez-Del-Alba A, Pinto A, Morales-Barrera R, Rodriguez-Vida A, Fernandez PL, Teixido C, Jares P, Aldecoa I, Gibson N, Solca F, Mondal S, Lorence RM, Serra J, Real FX. Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1). Br J Cancer. 2024 Feb;130(3):434-441. doi: 10.1038/s41416-023-02513-6. Epub 2023 Dec 15.

    PMID: 38102226DERIVED

Related Links

MeSH Terms

Conditions

Urologic Neoplasms

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Urogenital NeoplasmsNeoplasms by SiteNeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesUrologic Diseases

Intervention Hierarchy (Ancestors)

AmidesOrganic ChemicalsQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Limitations and Caveats

Duration of confirmed objective response was not analysed because only 2 patients showed a confirmed objective response. Instead, duration of disease control was analysed.

Results Point of Contact

Title
Boehringer Ingelheim, Call Center
Organization
Boehringer Ingelheim
clintriage.rdg@boehringer-ingelheim.com
1-800-243-0127

Study Officials

  • Boehringer Ingelheim

    Boehringer Ingelheim

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 20, 2016

First Posted

May 23, 2016

Study Start

June 9, 2016

Primary Completion

September 24, 2018

Study Completion

September 2, 2019

Last Updated

November 18, 2020

Results First Posted

October 12, 2020

Record last verified: 2020-10

Locations

IT(2)FR(9)ES(19)