Trial Outcomes & Findings for Avelumab in Combination With Fluorouracil and Mitomycin or Cisplatin and Radiation Therapy in Treating Participants With Muscle-Invasive Bladder Cancer (NCT NCT03617913)

Last Updated: 2023-01-06

Results Overview

Patients enrolled will have non-measurable disease based on imaging at baseline. Patients will be assessed for a response after 6 months of treatment using the results of a biopsy and cytology test. A complete response (CR) is defined as having a negative biopsy and negative urine cytology at 6 months from registration after finishing of concurrent RT and immunotherapy. Imaging of abdomen and pelvis confirming no systemic disease within 4 weeks of cystoscopy will be completed. The proportion of patients reporting a CR is reported here with confidence intervals for the true success proportion using the binomial distribution.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

At 6 months from registration

Results posted on

2023-01-06

Participant Flow

Participant milestones

Participant milestones
Measure	Avelumab and Cisplatin IV Participants received avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants received 35 mg/m\^2/day cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Avelumab in Combination With Fluorouracil and Mitomycin or Cisplatin and Radiation Therapy in Treating Participants With Muscle-Invasive Bladder Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Avelumab and Cisplatin IV n=2 Participants Participants received avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants received 35 mg/m\^2/day cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Age, Continuous	65 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: At 6 months from registration

Population: All patients who registered and began protocol treatment are included in this analysis.

Outcome measures

Outcome measures
Measure	Avelumab and Cisplatin IV n=2 Participants Participants received avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants received 35 mg/m\^2/day cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With Complete Response (At 6 Months)	0.5 proportion of participants Interval 0.013 to 0.987

SECONDARY outcome

Timeframe: Up to 12 months

Population: All patients who were registered, received protocol treatment, and were assessed for adverse events were included in this analysis.

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. The number of patients reporting a grade 3+ adverse event regardless of attribution is reported here.

Outcome measures

Outcome measures
Measure	Avelumab and Cisplatin IV n=2 Participants Participants received avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants received 35 mg/m\^2/day cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Adverse Events Per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade 3+ Adverse Event	2 Participants
Adverse Events Per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade 4+ Adverse Event	0 Participants

SECONDARY outcome

Timeframe: Baseline to 12 months

Population: All patients who were registered, treated, and completed the EORTC QLQ assessment at baseline and post-therapy were included in this analysis

EORTC QLQ-C30 is a 30-item patient-reported questionnaire. 28 of the 30 items are measured on a 1-4 scale (1=not at all; 4=very much) with the remaining two items (overall health and overall quality of life) scored on a 1-7 numeric analogue scale (1=very poor; 7=excellent). The recall period for the EORTC QLQ-C30 is one week. Changes from baseline will be statistically tested using paired t-tests, and standardized response means (mean of the change from baseline scores at a given cycle, divided by the standard deviation of the change scores) will be interpreted (after applying Middel's (2002) adjustment) using Cohen's (1988) cut-offs: \<0.20 = trivial; 0.20-\<0.50 = small; 0.50-\<0.80 = moderate; and \>=/0.80 = large. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 months

Population: All patients who were registered, treated, and completed the EORTC QLQ assessment at baseline and post-therapy were included in this analysis.

EORTC QLQ-BLM30 is a 30-item questionnaire for patients with muscle invasive bladder cancer (T2, T3, T4a and T4b). The muscle-invasive bladder cancer module contains additional items assessing urostomy problems, problems associated with the use of a catheter, and body image. Changes from baseline will be statistically tested using paired t-tests, and standardized response means (mean of the change from baseline scores at a given cycle, divided by the standard deviation of the change scores) will be interpreted (after applying Middel's (2002) adjustment) using Cohen's (1988) cut-offs: \<0.20 = trivial; 0.20-\<0.50 = small; 0.50-\<0.80 = moderate; and \>=/0.80 = large. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From registration to time of first documentation of progression or death from any cause, assessed up to 12 months

Population: All patients who registered and were treated are included in this analysis.

Progression-free survival is defined as the time from registration to the time of progression or death. This study will not use RECIST criteria to evaluate response or progression. The patients enrolled will have non-measurable disease on imaging and response will be evaluated with biopsy or cytology. Progression is defined as progression in T stage, N stage or M stage both clinically or radiologically. Histological confirmation of metastatic disease is at the discretion of the treating provider. The median time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Avelumab and Cisplatin IV n=2 Participants Participants received avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants received 35 mg/m\^2/day cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	NA years Too few events have occurred to obtain a median or a 95% CI.

SECONDARY outcome

Timeframe: From documented complete response to the first documentation of recurrence, assessed up to 12 months

Population: All patients who were registered, treated, and were assessed as having a Complete Response (CR) are eligible for this analysis. This endpoint can only be analyzed if more than one patient is eligible.

Recurrence-free survival is defined as the time from registration to the time of recurrence or death. Recurrence is defined as having histologically proven first appearance of muscle invasive bladder cancer, clinical evidence of metastatic disease, or treatment with radical cystectomy or radiation to the bladder, or death due to any cause after they were confirmed remission at 6 month evaluation. The median time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 months

Association of Bim (BCL-2-interacting mediator of cell death) expression will be evaluated at using the baseline tissue specimen and explored in relation to 6 months post-registration response and subsequently in relation to other clinical outcomes such as tumor response and adverse event incidence using two-way tables and analyzed using Fisher's exact tests.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 months

Association of Bim expression will be evaluated at using the baseline tissue specimen and explored in relation to 6 months post-registration response and subsequently in relation to other clinical outcomes such as tumor response and adverse event incidence using two-way tables and analyzed using Fisher's exact tests. Expression of immune signatures by RNA-seq expression (using the baseline tissue specimen) will be evaluated at baseline and explored in relation to clinical outcomes such as progression-free survival, tumor response, and adverse event incidence using two-way tables and box plots and analyzed using Fisher's exact tests or logistic regression methods, as appropriate.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 months

Outcome measures

Outcome data not reported

Adverse Events

Avelumab and Cisplatin IV

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Avelumab and Cisplatin IV n=2 participants at risk Participants received avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants received 35 mg/m\^2/day cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Infections and infestations Sepsis	50.0% 1/2 • Number of events 1 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.

Other adverse events

Other adverse events
Measure	Avelumab and Cisplatin IV n=2 participants at risk Participants received avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants received 35 mg/m\^2/day cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	50.0% 1/2 • Number of events 2 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Gastrointestinal disorders Constipation	100.0% 2/2 • Number of events 14 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Gastrointestinal disorders Diarrhea	50.0% 1/2 • Number of events 9 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Gastrointestinal disorders Nausea	50.0% 1/2 • Number of events 1 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Gastrointestinal disorders Proctitis	50.0% 1/2 • Number of events 1 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Gastrointestinal disorders Vomiting	50.0% 1/2 • Number of events 1 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
General disorders Fatigue	50.0% 1/2 • Number of events 13 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
General disorders Pain	50.0% 1/2 • Number of events 7 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Investigations Neutrophil count decreased	50.0% 1/2 • Number of events 1 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Investigations Platelet count decreased	50.0% 1/2 • Number of events 1 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Investigations White blood cell decreased	50.0% 1/2 • Number of events 2 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Psychiatric disorders Insomnia	50.0% 1/2 • Number of events 1 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Renal and urinary disorders Hematuria	50.0% 1/2 • Number of events 2 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Renal and urinary disorders Urinary frequency	100.0% 2/2 • Number of events 25 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Renal and urinary disorders Urinary incontinence	50.0% 1/2 • Number of events 2 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Renal and urinary disorders Urinary retention	50.0% 1/2 • Number of events 2 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Renal and urinary disorders Urinary tract pain	50.0% 1/2 • Number of events 1 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.
Renal and urinary disorders Urinary urgency	100.0% 2/2 • Number of events 9 • Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles. Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.

Additional Information

Parminder Singh, MD

Mayo Clinic

Phone: 5072555123

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place