Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Cisplatin-Ineligible or Refuse Cisplatin Therapy and Undergoing Radical Cystectomy MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864
Conditions
Interventions
Product Name: epacadostat
Product Code: INCB024360
Pharmaceutical Form: Tablet
Current Sponsor code: INCB024360
Other descriptive name: INCB024360
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to comprehend and willingness to sign a written ICF for the study. 2. Men or women aged 18 years or older. 3. Histologically confirmed transitional cell urothelial carcinoma. 4. Clinical stage T2-T3b, N0, M0 muscle invasive urothelial carcinoma by CT (or MRI) + PET/CT (Stage II-IIIA per AJCC 2018). a. Concomitant upper tract tumors should be excluded. 5. Ineligible for cisplatin therapy per modified Galsky criteria with exclusion of ECOG PS 2 participants a. Participants with CTCAE v4 = Grade 2 audiometric hearing loss (Galsky Criteria). b. Participants with CTCAE v4 = Grade 2 peripheral neuropathy (Galsky Criteria). c. Creatinine clearance of =65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: 1. Participation in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) before first dose. 2. Previously received systemic therapy for bladder cancer or received prior treatment with checkpoint inhibitor agents (such as anti–PD-1, anti–PD-L1, anti–PD-L2, or anti–CTLA-4). 3. Evidence of measurable nodal or metastatic disease. 4. Concurrent anticancer therapy 5. Has had major surgery within 4 weeks before enrollment (C1D1). 6. Has had known additional malignancy other than miUBC that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year, after treatment with curative intent. 7. Has active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg daily doses of prednisone or equivalent) or immunosuppressive drugs within 2 years of Day 1 of study treatment. 8. Participants with laboratory values at screening defined in the protocol 9. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent). 10. Has known active hepatitis B or C (defined as follows) or HIV, HBV, HCV, or hepatitis D virus coinfection: a. Active hepatitis B infection is defined by positive HBsAg and positive total anti-HBc results. b. Active hepatitis C is defined by a positive hepatitis C antibody result and quantitative HCV RNA results greater than lower limits of detection of the assay. 11. Participants who are known to be HIV-positive, unless all of the following criteria are met: a. CD4+ count = 300/µL. b. Undetectable viral load. c. Receiving antiretroviral therapy that is not a potential risk for a drug-drug interaction with the assigned study drugs. 12. Has known carcinomatous meningitis. 13. Active infection requiring systemic antibiotics = 14 days from first dose of study drug. 14. Participants with known or suspected COVID-19 infection. 15. Use of probiotics within 28 days from first dose of study drug. 16. Current use of prohibited medication 17. Has not recovered to = Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention before starting study therapy. 18. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. 19. History of a gastrointestinal condition (eg, inflammatory bowel disease, Crohn disease, ulcerative colitis) that may affect oral drug absorption. 20. Has received a live vaccine within 30 days of planned start of study therapy. 21. Participants with impaired cardiac function or clinically significant cardiac disease: a. New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy b. Unstable angina pectoris. c. Acute myocardial infarction = 6 months before study participation. d. Other clinically significant heart disease (eg, = Grade 3 hypertension). 22. Inability or unlikeliness to comply with the dose schedule and study evaluations, in the opinion of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine biologic response in participants with muscle-invasive cisplatin-ineligible or those refusing cisplatin therapy, urothelial carcinoma of the bladder.;Secondary Objective: To evaluate the safety and tolerability of each of the treatment groups. To evaluate the preliminary efficacy of each of the treatment groups.;Primary end point(s): For each treatment group, the primary endpoint is the change from baseline in CD8+ lymphocytes within resected tumor.;Timepoint(s) of evaluation of this end point: Safety will be performed throughout the study and the primary end point will be evaluated at the time of radical cystectomy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety and tolerability assessed by monitoring the frequency and severity of AEs, including delay in cystectomy due to AEs •pCR rate, defined as percentage of participants with ypT0N0 in each treatment group. • Major pathological response, defined as residual ypT0/1/a/isN0M0.;Timepoint(s) of evaluation of this end point: Safety will be performed throughout the study and the primary end point will be evaluated at the time of radical cystectomy | — |
Countries
France, Italy, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed