A Phase 2 clinical study to assess efficacy of Induction ipilimumab/nivolumab to spare the Bladder in urothelial bladder cancer (Indi-Blade)

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting3 sites in 1 country50 target enrollmentOctober 10, 2024

DrugsBMS936558 IBI310 ABP 206 NIVOLUMAB BMS734016 HLX13 IPILIMUMAB

Overview

Phase: Phase 1/2
Intervention: Not specified
Conditions: Not specified
Sponsor: Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Enrollment: 50
Locations: 3
Primary Endpoint: efficacy defined as bladder-intact event-free survival (BI-EFS). Events consist of death by any cause; muscle-invasive recurrence in the bladder or in the ureter, distal of the crossing with the common iliac artery, nodal or distant recurrence, cystectomy, or switch to cisplatin-based chemotherapy.
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

 To establish efficacy of induction ipilimumab + nivolumab followed by CRT by determining bladder-intact event-free survival (BI-EFS) for the intention-to-treat population. Events are defined as:

Muscle-invasive recurrence in the bladder or in the ureter, distal of the crossing with the common iliac artery
Nodal or distant recurrence
Cystectomy
Death by any cause
Switch to cisplatin-based chemotherapy

Registry

euclinicaltrials.eu

Start Date

October 10, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Responsible Party

Principal Investigator

Michiel van der Heijden

Scientific

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Eligibility Criteria

Inclusion Criteria

•Willing and able to provide informed consent
•Highly effective contraception for both male and female subjects if the risk of conception exists. Female patients of childbearing potential must comply with contraception methods as requested by the study protocol (→ 4.4 Pregnancy, contraception and breastfeeding)
•Age ≥ 18 years
•Patients with cT2-4aN0-2M0 urothelial bladder cancer, seeking an alternative to radical cystectomy and/or patients who are medically unfit for surgery. Patients with suspected metastatic disease are not eligible.
•Lymph node metastases should be amenable for inclusion into the radiation field according to the multidisciplinary tumor board and/or follow-up consultations between the treating physician and the radiation oncologist.
•World Health Organization (WHO) performance Status 0 or
•Urothelial cancer is the dominant histology (>70%). A small cell component is not allowed.
•Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available.
•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 as per Cockcroft-Gault formula, AST ≤ 2.5 x ULN, ALT ≤2.5 x ULN, Bilirubin ≤1.5 X ULN with an exception for patients with Gilbert’s syndrome (Bilirubin ≤2 X ULN)
•Negative pregnancy test (βHCG in urine or blood) for female patients of childbearing potential within 2 weeks prior to day 1 of start immunotherapy.

Exclusion Criteria

•Previous pelvic irradiation
•Known history of Human Immunodeficiency Virus, active tuberculosis, or other active infection requiring therapy at the time of inclusion.
•Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
•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 (e.g., CT scan premedication) will be allowed.
•Use of other investigational drugs four weeks or five half-lives 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 pelvic 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 2 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.

Outcomes

Primary Outcomes

efficacy defined as bladder-intact event-free survival (BI-EFS). Events consist of death by any cause; muscle-invasive recurrence in the bladder or in the ureter, distal of the crossing with the common iliac artery, nodal or distant recurrence, cystectomy, or switch to cisplatin-based chemotherapy.