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NCT02122172

Afatinib in Advanced Refractory Urothelial Cancer

Terminated Phase 2 Results posted Last updated 25 April 2025
What this trial tests

Phase 2 trial testing afatinib dimaleate in Distal Urethral Cancer in 32 participants. Terminated before completion.

Timeline
13 September 2017
Primary endpoint
4 April 2024
4 April 2024

Quick facts

Lead sponsorUniversity of Chicago
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment32
Start date13 September 2017
Primary completion4 April 2024
Estimated completion4 April 2024
Sites6 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Chicago

Who can join

18 and older, any sex, with Distal Urethral Cancer or Proximal Urethral Cancer. 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.

Progression-free Survival (PFS) Primary · 3 months

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and the sum must also demonstrate an absolute increase of at least 5mm, or unequivocal progression of existing non-target lesions, or the appearance of new lesions. Estimated at 3 months using the Kaplan-Meier method.

GroupValue95% CI
Treatment (Afatinib)5
Overall Response Rate Secondary · Up to 3 years

Includes both complete responses (CR) and partial responses (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR) is defined as the disappearance of all target lesions (any pathological lymph nodes must have reduction in short axis to \<10 mm); Partial Response (PR) is defined as \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

GroupValue95% CI
Treatment (Afatinib)2
Median Progression-free Survival (PFS ) Time Secondary · Up to 3 years

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and the sum must also demonstrate an absolute increase of at least 5mm, or unequivocal progression of existing non-target lesions, or the appearance of new lesions. Estimated using the Kaplan-Meier method.

GroupValue95% CI
Treatment (Afatinib)1.41.3 – 2.7
Median Overall Survival (OS) Time Secondary · Up to 3 years

Estimated using the Kaplan-Meier method.

GroupValue95% CI
Treatment (Afatinib)5.33.7 – 7.4
EGFR Expression Status Secondary · Baseline

These analyses were conducted using available archival formalin-fixed, paraffin-embedded sections from surgical specimens. Each sample was tested to determine whether there was EGFR amplification.

GroupValue95% CI
Treatment (Afatinib)5
HER2 Expression Status Secondary · Baseline

These analyses were conducted using available archival formalin-fixed, paraffin-embedded sections from surgical specimens. Each sample was tested to determine whether there was HER2 amplification.

GroupValue95% CI
Treatment (Afatinib)4

Adverse events — posted to ClinicalTrials.gov

Time frame: From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Afatinib) - Phase II Study
Serious: 11/23 (48%)
Deaths: 21/23
Treatment (Afatinib) - Molecularly Selected Cohort
Serious: 3/9 (33%)
Deaths: 9/9

Serious adverse events (19 terms)

ReactionSystemTreatment (Afatinib) - Pha…Treatment (Afatinib) - Mol…
Small bowel obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
LeukocytosisBlood and lymphatic system disorders
Edema limbsGeneral disorders
FeverGeneral disorders
Urinary tract infectionInfections and infestations
DyspneaRespiratory, thoracic and mediastinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
intracranial hemorrhage due to fallNervous system disorders
Skull fracture due to fallInjury, poisoning and procedural complications
Altered mental statusPsychiatric disorders
Coughing up bloodRespiratory, thoracic and mediastinal disorders
Stent revisionSurgical and medical procedures
DiarrheaGastrointestinal disorders
Mouth soresGeneral disorders
Indiana pouch obstructionProduct Issues
AnorexiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
Other adverse events (75 terms — click to expand)

ReactionSystemTreatment (Afatinib) - Pha…Treatment (Afatinib) - Mol…
Chronic kidney diseaseRenal and urinary disorders
Rash acneiformSkin and subcutaneous tissue disorders
DiarrheaGastrointestinal disorders
FatigueGeneral disorders
AnorexiaMetabolism and nutrition disorders
AnemiaBlood and lymphatic system disorders
Mucositis oralGastrointestinal disorders
PainGeneral disorders
NauseaGastrointestinal disorders
HematuriaRenal and urinary disorders
Creatinine increasedInvestigations
VomitingGastrointestinal disorders
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders
INR increasedInvestigations
LeukocytosisBlood and lymphatic system disorders
Edema limbsGeneral disorders
Urinary tract infectionInfections and infestations
HyperglycemiaMetabolism and nutrition disorders
FeverGeneral disorders
Penile infectionInfections and infestations
DyspneaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
DepressionPsychiatric disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
Alkaline phosphatase increasedInvestigations
ConfusionPsychiatric disorders
Productive coughRespiratory, thoracic and mediastinal disorders
HypomagnesemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Ejection fraction decreasedInvestigations
DysgeusiaNervous system disorders
Back painMusculoskeletal and connective tissue disorders
FallInjury, poisoning and procedural complications
Pain in extremityMusculoskeletal and connective tissue disorders
HypoalbuminemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Ileal obstructionGastrointestinal disorders
Tumor painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Penile painReproductive system and breast disorders

Most-reported serious reactions: Small bowel obstruction, Vomiting, Constipation, Leukocytosis, Edema limbs, Fever, Urinary tract infection, Dyspnea.

Data from ClinicalTrials.gov NCT02122172 adverse events section.

Sponsor's own description

This phase II trial studies how well afatinib dimaleate works in treating patients with urothelial cancer that cannot be removed surgically and has grown after treatment with standard first-line chemotherapy. Afatinib dimaleate may turn off the function of the epidermal growth factor (EGF) and human epidermal growth factor receptor 2 (HER2) receptors, which may slow the growth of cancer cells or cause some of the cells to die.

Publications & conference data

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

  1. Clinical and Biological Differences between Upper Tract Carcinoma and Bladder Urothelial Cancer, Including Implications for Clinical Practice.
    Lefort F, Rhanine Y, Larroquette M, Domblides C, et al · · 2023 · cited 10× · PMID 38067262 · DOI 10.3390/cancers15235558
  2. Advances in HER2-Targeted Treatment for Advanced/Metastatic Urothelial Carcinoma.
    Qu M, Zhou L, Yan X, Li S, et al · · 2023 · cited 9× · PMID 38155921 · DOI 10.14440/bladder.2023.871
  3. 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
  4. Upper tract urothelial carcinoma topical issue 2016: treatment of metastatic cancer.
    Pham MN, Apolo AB, De Santis M, Galsky MD, et al · · 2017 · cited 8× · PMID 27342991 · DOI 10.1007/s00345-016-1885-4
  5. Targeted Therapies in Advanced and Metastatic Urothelial Carcinoma.
    Katims AB, Reisz PA, Nogueira L, Truong H, et al · · 2022 · cited 7× · PMID 36358849 · DOI 10.3390/cancers14215431
  6. Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter.
    Bianconi M, Cimadamore A, Faloppi L, Scartozzi M, et al · · 2019 · cited 7× · PMID 30671136 · DOI 10.1177/1756287218815372
  7. New and Emerging Therapies in the Management of Bladder Cancer.
    Osterman CK, Milowsky MI. · · 2020 · cited 4× · PMID 32983413 · DOI 10.12688/f1000research.26841.1
  8. Enhancing immunotherapy through PD-L1 upregulation: the promising combination of anti-PD-L1 plus mTOR inhibitors.
    Hernández-Prat A, Rodriguez-Vida A, Cardona L, Qin M, et al · · 2025 · cited 3× · PMID 39258533 · DOI 10.1002/1878-0261.13699

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