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NCT03617913

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

Completed Phase 2 Results posted Last updated 6 January 2023
What this trial tests

Phase 2 trial testing Avelumab in Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall in 2 participants. Completed in 27 July 2020.

Timeline
19 September 2018
Primary endpoint
14 November 2019
27 July 2020

Quick facts

Lead sponsorMayo Clinic
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment2
Start date19 September 2018
Primary completion14 November 2019
Estimated completion27 July 2020
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Mayo Clinic

Who can join

18 and older, any sex, with Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall or Stage II Bladder Cancer AJCC v8. 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.

Proportion of Participants With Complete Response (At 6 Months) Primary · At 6 months from registration

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

GroupValue95% CI
Avelumab and Cisplatin IV0.50.013 – 0.987
Adverse Events Per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · Up to 12 months

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.

GroupValue95% CI
Avelumab and Cisplatin IV2
Avelumab and Cisplatin IV0
Progression-free Survival Secondary · From registration to time of first documentation of progression or death from any cause, assessed up to 12 months

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.

GroupValue95% CI
Avelumab and Cisplatin IVNANA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were assessed at the end of every 14 day cycle during treatment, up to 12 cycles.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Avelumab and Cisplatin IV
Serious: 1/2 (50%)
Deaths: 0/2

Serious adverse events (1 terms)

ReactionSystemAvelumab and Cisplatin IV
SepsisInfections and infestations
Other adverse events (18 terms — click to expand)

ReactionSystemAvelumab and Cisplatin IV
ConstipationGastrointestinal disorders
Urinary frequencyRenal and urinary disorders
Urinary urgencyRenal and urinary disorders
AnemiaBlood and lymphatic system disorders
DiarrheaGastrointestinal disorders
NauseaGastrointestinal disorders
ProctitisGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
PainGeneral disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
White blood cell decreasedInvestigations
InsomniaPsychiatric disorders
HematuriaRenal and urinary disorders
Urinary incontinenceRenal and urinary disorders
Urinary retentionRenal and urinary disorders
Urinary tract painRenal and urinary disorders

Most-reported serious reactions: Sepsis.

Data from ClinicalTrials.gov NCT03617913 adverse events section.

Sponsor's own description

This phase II trial studies the side effects of avelumab and how well it works in combination with fluorouracil and mitomycin or cisplatin and radiation therapy in treating participants with muscle-invasive bladder cancer. Monoclonal antibodies, such as avelumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as fluorouracil, mitomycin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving avelumab with chemotherapy and radiotherapy may work better in treating participants with muscle-invasive bladder cancer.

Publications & conference data

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

  1. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.
    Li K, Shi H, Zhang B, Ou X, et al · · 2021 · cited 687× · PMID 34620838 · DOI 10.1038/s41392-021-00670-9
  2. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  3. Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response.
    Daro-Faye M, Kassouf W, Souhami L, Marcq G, et al · · 2021 · cited 45× · PMID 32915313 · DOI 10.1007/s00345-020-03440-4
  4. Improving Anti-PD-1/PD-L1 Therapy for Localized Bladder Cancer.
    de Jong FC, Rutten VC, Zuiverloon TCM, Theodorescu D. · · 2021 · cited 40× · PMID 33802033 · DOI 10.3390/ijms22062800
  5. Myeloid-Derived Suppressor Cells: Implications in the Resistance of Malignant Tumors to T Cell-Based Immunotherapy.
    Shi H, Li K, Ni Y, Liang X, et al · · 2021 · cited 26× · PMID 34336860 · DOI 10.3389/fcell.2021.707198
  6. Bladder-sparing protocols in the treatment of muscle-invasive bladder cancer.
    Tholomier C, Souhami L, Kassouf W. · · 2020 · cited 22× · PMID 33457265 · DOI 10.21037/tau.2020.02.10
  7. Role of immunotherapy in localized muscle invasive urothelial cancer.
    Kaur J, Choi W, Geynisman DM, Plimack ER, et al · · 2021 · cited 15× · PMID 34567274 · DOI 10.1177/17588359211045858
  8. Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective.
    Bleve A, Consonni FM, Porta C, Garlatti V, et al · · 2022 · cited 10× · PMID 35158779 · DOI 10.3390/cancers14030510

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