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NCT02780687: LUX-Bladder 1

Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy

Completed Phase 2 Results posted Last updated 18 November 2020
What this trial tests

Phase 2 trial testing Afatinib in Urologic Neoplasms in 42 participants. Completed in 2 September 2019.

Timeline
9 June 2016
Primary endpoint
24 September 2018
2 September 2019

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment42
Start date9 June 2016
Primary completion24 September 2018
Estimated completion2 September 2019
Sites30 locations across France, Spain, Italy

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Urologic Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Progression-free Survival at Six Months (PFS6) in Cohort A Primary · 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. Progress

GroupValue95% CI
Cohort A4
Number of Participants With Confirmed Objective Response (ORR) in Cohort A Secondary · 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 perform

GroupValue95% CI
Cohort A2
Progression-free Survival (PFS) in Cohort A Secondary · 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 ha

GroupValue95% CI
Cohort A9.87.9 – 16.0
Overall Survival (OS) in Cohort A Secondary · 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.

GroupValue95% CI
Cohort A30.117.4 – 47.0
Number of Participants With Disease Control (DCR) in Cohort A Secondary · 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) o

GroupValue95% CI
Cohort A17
Cohort A17
Duration of Disease Control in Cohort A Secondary · 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

GroupValue95% CI
Cohort A22.715.1 – 36.1
Number of Patients With Tumour Shrinkage in Cohort A Secondary · 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

GroupValue95% CI
Cohort A9

Adverse events — posted to ClinicalTrials.gov

Time frame: From the time of first drug administration till the end of treatment + 30 days (REP), up to approximately 20 Months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A
Serious: 15/34 (44%)
Deaths: 26/34
Cohort B
Serious: 6/8 (75%)
Deaths: 7/8

Serious adverse events (30 terms)

ReactionSystemCohort ACohort B
DiarrhoeaGastrointestinal disorders
Urinary tract infectionInfections and infestations
AnaemiaBlood and lymphatic system disorders
Acute coronary syndromeCardiac disorders
Cardiac failureCardiac disorders
DysphagiaGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
PainGeneral disorders
PyrexiaGeneral disorders
Escherichia pyelonephritisInfections and infestations
Infected skin ulcerInfections and infestations
InfluenzaInfections and infestations
Pelvic abscessInfections and infestations
Respiratory tract infectionInfections and infestations
Urinary tract infection bacterialInfections and infestations
CachexiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
FistulaMusculoskeletal and connective tissue disorders
Groin painMusculoskeletal and connective tissue disorders
Musculoskeletal disorderMusculoskeletal and connective tissue disorders
Osteonecrosis of jawMusculoskeletal and connective tissue disorders
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (67 terms — click to expand)

ReactionSystemCohort ACohort B
DiarrhoeaGastrointestinal disorders
AstheniaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Mucosal inflammationGeneral disorders
NauseaGastrointestinal disorders
StomatitisGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
Urinary tract infectionInfections and infestations
PruritusSkin and subcutaneous tissue disorders
HypomagnesaemiaMetabolism and nutrition disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
Skin toxicitySkin and subcutaneous tissue disorders
DyspepsiaGastrointestinal disorders
PainGeneral disorders
XerosisGeneral disorders
ParonychiaInfections and infestations
Pain in extremityMusculoskeletal and connective tissue disorders
Renal failureRenal and urinary disorders
Dry skinSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
Oedema peripheralGeneral disorders
Respiratory tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Blood creatine phosphokinase increasedInvestigations
Blood creatinine increasedInvestigations
CachexiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Bone painMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
Neuropathy peripheralNervous system disorders
ParaesthesiaNervous system disorders
InsomniaPsychiatric disorders

Most-reported serious reactions: Diarrhoea, Urinary tract infection, Anaemia, Acute coronary syndrome, Cardiac failure, Dysphagia, Intestinal obstruction, Nausea.

Data from ClinicalTrials.gov NCT02780687 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Prevalence and role of HER2 mutations in cancer.
    Cocco E, Lopez S, Santin AD, Scaltriti M. · · 2019 · cited 73× · PMID 30951733 · DOI 10.1016/j.pharmthera.2019.03.010
  2. Emerging biomarkers and targeted therapies in urothelial carcinoma.
    Mendiratta P, Grivas P. · · 2018 · cited 27× · PMID 30069452 · DOI 10.21037/atm.2018.05.49
  3. Predictive and Prognostic Biomarkers and Tumor Antigens for Targeted Therapy in Urothelial Carcinoma.
    Eturi A, Bhasin A, Zarrabi KK, Tester WJ. · · 2024 · cited 13× · PMID 38675715 · DOI 10.3390/molecules29081896
  4. Systemic treatment for advanced urothelial cancer: an update on recent clinical trials and current treatment options.
    Park I, Lee JL. · · 2020 · cited 12× · PMID 32668516 · DOI 10.3904/kjim.2020.204
  5. Genomics and Immunomics in the Treatment of Urothelial Carcinoma.
    Mollica V, Massari F, Rizzo A, Ferrara R, et al · · 2022 · cited 10× · PMID 35621673 · DOI 10.3390/curroncol29050283
  6. Emerging agents for the treatment of metastatic urothelial cancer.
    Kwon WA, Seo HK. · · 2021 · cited 9× · PMID 33943047 · DOI 10.4111/icu.20200597
  7. Precision oncology in urothelial cancer.
    Liow E, Tran B. · · 2020 · cited 9× · PMID 32132102 · DOI 10.1136/esmoopen-2019-000616
  8. Elucidation of Novel Molecular Targets for Therapeutic Strategies in Urothelial Carcinoma: A Literature Review.
    Nelson BE, Hong A, Jana B. · · 2021 · cited 8× · PMID 34422659 · DOI 10.3389/fonc.2021.705294

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