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

Phase 2

Recruiting

• Conditions: Urothelial carcinoma of the bladder and bladder cancer; 10038364

• Registration Number: NL-OMON52087
• Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

1. Willing and able to provide informed consent
2. Age >= 18 years
3. 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.
4. Lymph nodes 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.
5. World Health Organization (WHO) performance Status 0 or 1.
6. Urothelial cancer is the dominant histology (>70%). %). A small cell
component is not allowed.
7. Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks
from diagnostic TUR available.
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 as per Cockcroft-Gault formula, AST <= 2.5 x ULN, ALT <=2.5
x ULN, Bilirubin <=1.5 X ULN
9. Negative pregnancy test (βHCG in urine or blood) for female patients of
childbearing potential within 2 weeks prior to day 1 of start immunotherapy.
10. 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

Exclusion Criteria

1. Previous pelvic irradiation
2. Upper tract urothelial cancer
3. Extensive CIS of the bladder
4. Bilateral hydronephrosis
5. Previous intravenous chemotherapy for bladder cancer
6. Contra-indication to one of the study treatment components, or mpMRI
7. 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
8. Documented history of severe autoimmune disease (e.g. inflammatory bowel
disease, myasthenia gravis)
9. Prior CTLA-4 or PD-(L)1 -targeting immunotherapy
10. Known history of Human Immunodeficiency Virus, active tuberculosis, or
other active infection requiring therapy at the time of inclusion
11. Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic
acid (RNA)
12. Underlying medical conditions that, in the investigator's opinion, will
make the administration of study drug hazardous or obscure the interpretation
of adverse events
13. 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
14. Use of other investigational drugs four weeks or five half lifes before
study drug administration
15. 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
16. Pregnant and lactating female patients
17. 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
18. 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Efficacy defined as bladder-intact event-free survival (BI-EFS)<br /><br>Primary endpoint readout will be BI-EFS. Events are defined as death by any<br /><br>cause, muscle-invasive recurrence in the bladder or in the ureter, distal of<br /><br>the crossing with the common iliac artery, nodal or distant recurrencee,<br /><br>cystectomy, or switch to cisplatin-based chemotherapy.<br /><br>BI-EFS will be determined starting from the initiation of the study drug by<br /><br>CT-imaging, mpMRI of the bladder and cystoscopy. At the time of analysis,<br /><br>patients without an event will be censored at the time point of their last CT,<br /><br>mpMRI of the bladder or cystoscopy assessment.</p><br>