Status:
COMPLETED
Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy
Lead Sponsor:
The Netherlands Cancer Institute
Collaborating Sponsors:
Bristol-Myers Squibb
Conditions:
Urothelial Carcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
In cohort 1 of this study, we used an attenuated schedule of neoadjuvant ipilimumab and nivolumab. In the multicenter extension (cohort 2), 30 patients were randomized between two neoadjuvant treatmen...
Detailed Description
This is an open-label phase Ib trial to evaluate three different schedules of preoperative ipilimumab and nivolumab. Urothelial cancer patients will be included that are diagnosed with either: * cT3-...
Eligibility Criteria
Inclusion
- Willing and able to provide informed consent
- Age ≥ 18 years
- High-risk resectable urothelial cancer (upper urinary tract allowed) defined as stage III UC:
- cT3-4aN0M0 OR cT1-4aN1-3M0 4. Refusal of neoadjuvant/induction cisplatin-based chemotherapy or patients in whom neoadjuvant cisplatin based therapy is not appropriate.
- 5\. World Health Organization (WHO) performance Status 0 or 1. 6. Urothelial cancer is the dominant histology (\>70%). 7. Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available (or any other FFPE tumor specimens for upper tract tumors).8. 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 ≤ 2.5 x ULN, ALT ≤2.5 x ULN, Bilirubin ≤1.5 X ULN 9. Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
- 10\. For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate \[\<1% per year\] when used consistently and correctly) and to continue its use for 180 days after the last dose of immunotherapy Adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms, oral contraceptives, intra-uterine device.
Exclusion
- 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.
- Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).
- Prior CTLA-4 or PD-1/PD-L1-targeting immunotherapy.
- Known history of Human Immunodeficiency Virus, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA), active tuberculosis, or other active infection requiring therapy at the time of inclusion.
- Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events
- Medical condition requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) will be allowed.
- Use of other investigational drugs before study drug administration
- Malignancy, other than urothelial cancer, in the previous 2 years, with a high chance of recurrence (estimated \>10%). Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score
- ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
- Pregnant and lactating female patients.
- 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.
- Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
- 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, or unstable angina.
- Previous intravenous chemotherapy for bladder cancer. Prior chemoradiation is allowed.
- Patients in whom use of a colon segment for urinary diversion is planned
Key Trial Info
Start Date :
January 15 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 7 2025
Estimated Enrollment :
54 Patients enrolled
Trial Details
Trial ID
NCT03387761
Start Date
January 15 2018
End Date
January 7 2025
Last Update
March 5 2025
Active Locations (3)
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1
Antoni van Leeuwenhoek ziekenhuis
Amsterdam, North Holland, Netherlands, 1066CX
2
Radboud UMC
Nijmegen, Netherlands
3
UMC Utrecht
Utrecht, Netherlands