Trial Outcomes & Findings for Afatinib in Advanced Refractory Urothelial Cancer (NCT NCT02122172)

Last Updated: 2025-04-25

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

3 months

Results posted on

2025-04-25

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Afatinib) Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO laboratory biomarker analysis: Correlative studies
Overall Study STARTED	32
Overall Study Main Phase II Study	23
Overall Study Molecularly Selected Cohort	9
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Afatinib in Advanced Refractory Urothelial Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Afatinib) - Phase II Study n=23 Participants Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO Enrolled as part of the main Phase II study	Treatment (Afatinib) - Molecularly Selected Cohort n=9 Participants Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO Enrolled as part of the molecularly selected cohort	Total n=32 Participants Total of all reporting groups
Age, Continuous	67 years n=5 Participants	70 years n=7 Participants	69 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	7 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	8 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	8 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	23 Participants n=5 Participants	9 Participants n=7 Participants	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Population: Analysis population included those in the main Phase II study

Outcome measures

Outcome measures
Measure	Treatment (Afatinib) n=23 Participants Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO laboratory biomarker analysis: Correlative studies
Progression-free Survival (PFS)	5 Participants

SECONDARY outcome

Timeframe: Up to 3 years

Population: Analysis population includes those patients in the main Phase II study

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.

Outcome measures

Outcome measures
Measure	Treatment (Afatinib) n=23 Participants Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO laboratory biomarker analysis: Correlative studies
Overall Response Rate	2 Participants

SECONDARY outcome

Timeframe: Up to 3 years

Population: Analysis population includes patients from the main Phase II study

Outcome measures

Outcome measures
Measure	Treatment (Afatinib) n=23 Participants Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO laboratory biomarker analysis: Correlative studies
Median Progression-free Survival (PFS ) Time	1.4 months Interval 1.3 to 2.7

SECONDARY outcome

Timeframe: Up to 3 years

Population: Analysis population includes those in the main Phase II study

Estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Treatment (Afatinib) n=23 Participants Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO laboratory biomarker analysis: Correlative studies
Median Overall Survival (OS) Time	5.3 months Interval 3.7 to 7.4

SECONDARY outcome

Timeframe: Baseline

Population: The analysis sample included those in the main Phase II study. Two patients did not have a sample to analyze.

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.

Outcome measures

Outcome measures
Measure	Treatment (Afatinib) n=21 Participants Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO laboratory biomarker analysis: Correlative studies
EGFR Expression Status	5 Participants

SECONDARY outcome

Timeframe: Baseline

Population: Analysis population included those in the main Phase II study. Two patients did not have a sample to analyze

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.

Outcome measures

Outcome measures
Measure	Treatment (Afatinib) n=21 Participants Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO laboratory biomarker analysis: Correlative studies
HER2 Expression Status	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: This outcome measure was not assessed.

Relationship to 3-month PFS will be determined.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: This outcome measure was not assessed.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Afatinib) - Phase II Study

Serious events: 11 serious events

Other events: 23 other events

Deaths: 21 deaths

Treatment (Afatinib) - Molecularly Selected Cohort

Serious events: 3 serious events

Other events: 9 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Peter O'Donnell

University of Chicago

Phone: (773) 702-7564

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Treatment (Afatinib) - Phase II Study n=23 participants at risk Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO Enrolled as part of the main Phase II study	Treatment (Afatinib) - Molecularly Selected Cohort n=9 participants at risk Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. afatinib dimaleate: Given PO Enrolled as part of the molecularly selected cohort
Gastrointestinal disorders Small bowel obstruction	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Gastrointestinal disorders Vomiting	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Gastrointestinal disorders Constipation	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Blood and lymphatic system disorders Leukocytosis	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
General disorders Edema limbs	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
General disorders Fever	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Infections and infestations Urinary tract infection	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Musculoskeletal and connective tissue disorders Pain in extremity	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Nervous system disorders intracranial hemorrhage due to fall	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Injury, poisoning and procedural complications Skull fracture due to fall	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Psychiatric disorders Altered mental status	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Respiratory, thoracic and mediastinal disorders Coughing up blood	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Surgical and medical procedures Stent revision	4.3% 1/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	0.00% 0/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Gastrointestinal disorders Diarrhea	0.00% 0/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	11.1% 1/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
General disorders Mouth sores	0.00% 0/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	11.1% 1/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Product Issues Indiana pouch obstruction	0.00% 0/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	11.1% 1/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Metabolism and nutrition disorders Anorexia	0.00% 0/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	11.1% 1/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.
Gastrointestinal disorders Abdominal pain	0.00% 0/23 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.	11.1% 1/9 • From the initiation of treatment to 28 days after the last administration of trial drugs, up to 1 year For the Other Adverse Events, the number of participants reported for each adverse event is an upper bound estimate.