A Phase 1b trial in Stage II-III urothelial cancer to explore pre-operative immunotherapy - TURANDOT

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

1. Resectable muscle-invasive UC (upper urinary tract allowed), defined as:
- cT2-4aN0M0 OR
- cT1-4aN1-3M0
2. World Health Organization (WHO) performance Status 0 or 1.
3. Urothelial cancer is the dominant histology (>70%).
4. PD-L1 status must be determined using the 22C3 pharmDx test. Combined
positivity score (CPS) must be >10 under amendment V3.
5. Screening laboratory values must meet the following criteria: WBC >=
2.0x109/L, Neutrophils >=1.0x109/L, Platelets >=100 x109/L, Hemoglobin >=5.5
mmol/L, GFR>30 ml/min, AST <= 1.5 x ULN, ALT <=1.5 x ULN, Bilirubin <=1.5 X ULN
6. Negative pregnancy test
7. Age >= 18 years

Exclusion Criteria

1. Subjects with active autoimmune disease in the past 2 years. Patients with
diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism,
vitiligo, psoriasis or other mild skin disease can still be included.
2. Documented history of severe autoimmune disease (e.g. inflammatory bowel
disease, myasthenia gravis).
3. Prior CTLA-4 or PD-1/PD-L1-targeting immunotherapy.
4. Known history of Human Immunodeficiency Virus infection, or tuberculosis, or
other active infection requiring therapy at the time of inclusion.
5. Positive tests for Hepatitis B or Hepatitis C
6. Underlying medical conditions that, in the investigator's opinion, will make
the administration of study drug hazardous or obscure the interpretation of
adverse events
7. Medical condition requiring the use of immunosuppressive medications
8. Use of other investigational drugs before study drug administration
9. Malignancy, other than urothelial cancer, in the previous 2 years, with a
high chance of recurrence (estimated >10%).
10. Pregnant and lactating female patients.
11. Major surgical procedure within 4 weeks prior to enrolment or anticipation
of need for a major surgical procedure during the course of the study other
than for diagnosis.
12. Severe infections within 2 weeks prior to enrolment in the study
13. Significant cardiovascular disease, such as New York Heart Association
cardiac disease (Class II or greater), myocardial infarction within 3 months
prior to enrolment, unstable arrhythmias and unstable angina.
14. Previous intravenous chemotherapy for bladder cancer. Prior low-dose
sensitizing chemotherapy used for combined modality treatment, or radiation
alone, is allowed if patients have recurred after an initial response. Patients
with residual disease after (chemo)radiation for bladder cancer are not
eligible.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is feasibility, defined as the number of patients<br /><br>undergoing cystectomy within 12 weeks after start of the study drug. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Efficacy: Efficacy will be defined as the percentage of pathological<br /><br>complete response (pCR), defined as pT0N0 or pTisN0, at cystectomy. Other<br /><br>efficacy endpoints will include RFS and OS.<br /><br>2. Safety: We will provide the frequency of treatment-related toxicities as<br /><br>measured according to CTCAE 5.0.<br /><br>3. Translational: Effects of immunotherapy on the UC tumor microenvironment</p><br>