Distal Urethral CancerPhase 2NCT02122172
Afatinib in Advanced Refractory Urothelial Cancer
A Phase 2 study testing afatinib dimaleate and laboratory biomarker analysis in people with Distal Urethral Cancer and Proximal Urethral Cancer, run by University of Chicago at 6 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Distal Urethral Cancer, Proximal Urethral Cancer, Recurrent Bladder Cancer
- What is being tested?
- afatinib dimaleate and laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 6 sitesUnited States
- Study dates
- 13 Sep 2017to 4 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment
- Patients must have histologically or cytologically confirmed urothelial tract carcinoma; patients with urothelial carcinoma of the bladder, upper tract, or urethra are eligible
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan for the evaluation of measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1])
- Patients must have evidence of disease progression prior to enrollment
- All patients must have received a prior platinum-based chemotherapy regimen for treatment of urothelial cancer and must now be considered refractory to platinum-based chemotherapy; patients may have received the platinum-containing regimen either in the peri-operative or metastatic setting
- Patients may have received up to one line of prior systemic chemotherapy for recurrent/metastatic disease; if a platinum-based regimen was received both in the peri-operative setting and again in the metastatic setting, this will be considered 1 line of chemotherapy
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- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
- Hemoglobin >= 8.5g/dL
- Total bilirubin =< 1.5 institutional upper limit of normal (IULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X IULN
- Calculated creatinine clearance >= 30 mL/min by the modified Cockcroft and Gault Formula OR glomerular filtration rate >= 30 mL/min/body surface area (BSA) by Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
- Women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Patients must have the ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients may not be receiving any other investigational agents
- Patients with untreated known brain metastases, or treated brain metastases that are clinically unstable
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
- Women known to be pregnant
- Women who are breastfeeding and who are unwilling to stop breastfeeding prior to study entry
- Patients with known prior human immunodeficiency virus (HIV)-positive status on combination antiretroviral therapy are ineligible; known prior HIV-positive patients with CD4+ =< 500/mm^3 are ineligible (HIV testing is not required as part of this study)
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- Pre-existing interstitial lung disease
- Inability to take oral medications
- Prior therapy with afatinib
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
University of North Carolina - Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
University of Chicago
Chicago, Illinois, 60637
Decatur Memorial Hospital
Decatur, Illinois, 62526
NorthShore University Health System
Evanston, Illinois, 60201
NYU Langone Health
New York, New York, 10016
About this study
Official title: Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the 3-month progression free survival (PFS) rate in metastatic urothelial cancer patients receiving afatinib (afatinib dimaleate) who have progressed despite prior platinum-based chemotherapy.
SECONDARY OBJECTIVES:
- To determine the overall response rate (complete response [CR] + partial response [PR]), median progression free survival, and overall survival for the same treated population.
II. To determine whether tumor epidermal growth factor receptor (EGFR) and/or HER2 overexpression influences 3-month PFS in patients treated with afatinib.
OUTLINE:
Patients receive afatinib dimaleate orally (PO) once daily (QD) on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
- Conditions
- Distal Urethral Cancer, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Urethral Cancer, Stage III Bladder Cancer, Stage III Urethral Cancer
- Being tested
- afatinib dimaleate, laboratory biomarker analysis
- Medical subject headings
- Urinary Bladder Neoplasms, Urethral Neoplasms, Ureteral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
afatinib dimaleateDrug
Also called afatinib, BIBW 2992 MA2, Gilotrif
Given PO
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (afatinib) | Experimental | Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: afatinib dimaleate; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
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.
Measured: 3 months
Secondary outcomes (5)
Overall Response Rate
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.
Measured: Up to 3 years
Median Progression-free Survival (PFS ) Time
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.
Measured: Up to 3 years
Median Overall Survival (OS) Time
Estimated using the Kaplan-Meier method.
Measured: Up to 3 years
EGFR Expression Status
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.
Measured: Baseline
HER2 Expression Status
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2014 (estimated)
- Study start13 Sep 2017
- Primary completion4 Apr 2024
- Study completion4 Apr 2024
Why it stopped: Unable to meet accrual goal after several years
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Distal Urethral CancerStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Peter O'Donnell, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02122172
- Sponsor's protocol ID
- 13-0540
- Other IDs
- NCI-2014-00859, IRB13-0540, 13-0540/ 1200.171, P30CA014599
- Status last verified
- Apr 2025
- First submitted
- 22 Apr 2014
- Last updated
- 25 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer
- ClinicalTrials.gov ID
- NCT02122172
- Acronym / sponsor ID
- 13-0540
- Conditions
- Distal Urethral Cancer, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Urethral Cancer, Stage III Bladder Cancer, Stage III Urethral Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to meet accrual goal after several years
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Sep 2017 (actual)
- Primary completion
- 4 Apr 2024 (actual)
- Study completion
- 4 Apr 2024 (actual)
- First posted
- 24 Apr 2014 (estimated)
- Results
- Posted 25 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the 3-month progression free survival (PFS) rate in metastatic urothelial cancer patients receiving afatinib (afatinib dimaleate) who have progressed despite prior platinum-based chemotherapy.
SECONDARY OBJECTIVES:
- To determine the overall response rate (complete response [CR] + partial response [PR]), median progression free survival, and overall survival for the same treated population.
II. To determine whether tumor epidermal growth factor receptor (EGFR) and/or HER2 overexpression influences 3-month PFS in patients treated with afatinib.
OUTLINE:
Patients receive afatinib dimaleate orally (PO) once daily (QD) on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (afatinib) | Experimental | Drug: afatinib dimaleate, Other: laboratory biomarker analysisPatients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment
- Patients must have histologically or cytologically confirmed urothelial tract carcinoma; patients with urothelial carcinoma of the bladder, upper tract, or urethra are eligible
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan for the evaluation of measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1])
- Patients must have evidence of disease progression prior to enrollment
- All patients must have received a prior platinum-based chemotherapy regimen for treatment of urothelial cancer and must now be considered refractory to platinum-based chemotherapy; patients may have received the platinum-containing regimen either in the peri-operative or metastatic setting
Key exclusion criteria (9 listed)
- Patients may not be receiving any other investigational agents
- Patients with untreated known brain metastases, or treated brain metastases that are clinically unstable
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
- Women known to be pregnant
- Women who are breastfeeding and who are unwilling to stop breastfeeding prior to study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| afatinib dimaleateAlso: afatinib, BIBW 2992 MA2, GilotrifGiven PO | Drug | Treatment (afatinib) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (afatinib) |
Primary outcome
Progression-free Survival (PFS)
Time frame: 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.
5 secondary outcomes
Overall Response Rate
Time frame: Up to 3 years
Median Progression-free Survival (PFS ) Time
Time frame: Up to 3 years
Median Overall Survival (OS) Time
Time frame: Up to 3 years
EGFR Expression Status
Time frame: Baseline
HER2 Expression Status
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Distal Urethral Cancer
Active, not recruitingPhase 2
Fluorouracil, Leucovorin, Gemcitabine, and Cisplatin in Treating Patients With Metastatic or Unresectable Adenocarcinoma of the Urothelium or Urachal Remnant
Bladder Cancer, Urethral Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter O'Donnell principal investigator
University of Chicago
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing afatinib dimaleate and laboratory biomarker analysis in people with Distal Urethral Cancer and Proximal Urethral Cancer, run by University of Chicago at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2025.