Actively Recruiting
A Phase 1b-2 Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer
Led by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Updated on 2022-08-12
50
Participants Needed
3
Research Sites
104 weeks
Total Duration
On this page
Sponsors
A
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Lead Sponsor
B
Bristol-Myers Squibb
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a combination of chemotherapy, radiation, and immunotherapy for adults with non-metastatic muscle invasive bladder cancer who are eligible for chemoradiotherapy with the goal of preserving the bladder. This phase 1b/2, open-label study aims to assess the feasibility, safety, and disease-free survival outcomes of adding immunotherapy drugs nivolumab alone or combined with ipilimumab to standard chemoradiotherapy treatments. Participants receive one of three treatment regimens: nivolumab monotherapy given intravenously every 4 weeks for 3 doses, or nivolumab combined with ipilimumab at different dosing schedules every 3 weeks for 4 doses. After these initial treatments, all participants may continue nivolumab monotherapy every 4 weeks for up to 10 additional doses, extending treatment from week 13 through week 52. During the study, participants undergo regular monitoring for treatment side effects using standard toxicity scoring within 6 weeks of starting therapy. Researchers measure disease-free survival, overall survival, response rates, and long-term safety over a 5-year period. Assessments include clinical exams, laboratory tests, and imaging to track disease status and side effects throughout the study duration.
CONDITIONS
Brief Title
A Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Be willing and able to provide written informed consent for the trial.
- Be 18 years of age or older at consent.
- Desire to preserve bladder function or be ineligible for cystectomy.
- Have histologically-confirmed muscle-invasive T2-T4a, N0-1M0 urothelial cell carcinoma of the bladder.
- Have undergone transurethral biopsy and maximal transurethral resection of the bladder tumor within 35 days before treatment.
- Have predominantly urothelial cell carcinoma (>50%); mixed histology allowed.
- Have planned chemoradiotherapy as definitive treatment.
- Have ECOG performance status 0 or 1.
- Have bladder accessible for cystoscopic follow-up.
- Demonstrate adequate organ function with labs within 28 days prior to trial registration.
- Female participants of childbearing potential must have a negative pregnancy test within 72 hours before registration and use highly effective contraception or abstain during study and 5 months after last dose.
- Male participants must agree to use condoms from first dose through 7 months after last dose.
- Consent to use of tumor, blood, and urine samples for future research.
You will not qualify if you...
- Have DPD deficiency.
- Have concurrent extra-vesical urothelial cell carcinoma except safely included prostatic urethra involvement.
- Have extensive or multifocal bladder carcinoma in situ preventing curative chemoradiotherapy.
- Have distant metastatic disease except up to 3 pelvic lymph nodes included in radiation field.
- Prior pelvic lymphadenectomy or pelvic radiotherapy.
- Prior intravenous chemotherapy, targeted therapy, or radiation for bladder cancer.
- Unsuitable for concurrent MMC/capecitabine chemoradiotherapy due to medical conditions.
- Currently participating in another investigational study or received investigational therapy within 4 weeks.
- Have immunodeficiency, systemic steroid therapy over 10mg prednisone daily, or immunosuppressive therapy within 14 days prior.
- Known active tuberculosis.
- Hypersensitivity to nivolumab, ipilimumab, or excipients.
- Prior or concurrent additional malignancy unless disease free for 5 years with some exceptions.
- History of active autoimmune disease, Stevens-Johnson syndrome, or Guillain-Barre except controlled hypothyroidism or Type I diabetes.
- Known active non-infectious pneumonitis or active infection requiring systemic therapy.
- Conditions interfering with participation or study results per investigator judgment.
- Psychiatric or substance abuse disorders impacting cooperation.
- Pregnant, breastfeeding, or planning conception during study or 120 days after last dose.
- Prior therapy with anti-PD-1, PD-L1, or PD-L2 agents.
- HIV infection with detectable viral load.
- Active Hepatitis B or C infection.
- Received live vaccine within 30 days before study therapy start except inactivated flu vaccines allowed, intranasal flu vaccines not allowed.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 13 weeks for initial treatment
Participants receive immuno-chemoradiotherapy with one of three regimens combining mitomycin-c/capecitabine chemoradiation with nivolumab monotherapy or nivolumab and ipilimumab combination therapy.
3 to 4 intravenous infusions every 3 or 4 weeks depending on regimen
Duration - Up to 40 weeks from week 13 to week 52
Participants may receive additional nivolumab monotherapy administrations at 480mg intravenously every 4 weeks as optional extended treatment.
Up to 10 intravenous infusions every 4 weeks
Duration - Up to 5 years
Participants are monitored for disease-free survival, overall survival, and response for up to 5 years after treatment.
Periodic visits as determined by study team
Trial Site Locations
Total: 3 locations
1
Amsterdam UMC, VUmc
Amsterdam, North Holland, Netherlands, 1081 HV
Actively Recruiting
2
Amsterdam UMC, AMC
Amsterdam, North Holland, Netherlands, 1105 AZ
Actively Recruiting
3
LUMC
Leiden, South Holland, Netherlands
Actively Recruiting
Research Team
A
Adriaan D. Bins, MD PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
FACTORIAL
Primary Purpose
TREATMENT
Number of Arms
3
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