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

  • STATUS
    Recruiting
  • End date
    Jan 25, 2023
  • participants needed
    50
  • sponsor
    Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Updated on 25 January 2021
combination therapy
serum pregnancy test
carcinoma
mitomycin
nivolumab
ipilimumab
bladder cancer
invasive bladder cancer
transurethral resection
bladder tumor
bladder carcinoma
carcinoma of the bladder

Summary

A multicenter Phase 1b/2, two stage, open label study of MMC/Capecitabine ChRT combined with nivolumab monotherapy or nivolumab and ipilimumab combination therapy in adult (>18 years) subjects with non-metastatic muscle invasive bladder cancer that qualify for ChRT with curative intent.

Description

Immunotherapy combined with chemoradiation for localized bladder cancer may exhibit improved efficacy with an acceptable toxicity profile.

The aim of this phase 1b/2, two stage, open label study of MMC/Capecitabine ChRT combined with nivolumab monotherapy or nivolumab and ipilimumab combination therapy stuy is: to assess the feasibility and safety, the disease free survival (DFS) and disease free survival rate (DFS-rate) of the addition of nivolumab and/or ipilimumab to MMC/capecitabine chemoradiation of the bladder.

Details
Condition urinary tract neoplasm, bladder cancer, bladder disorder, Urothelial Cancer, Invasive Bladder Cancer, Bladder Disorders, Bladder Carcinoma, Urologic Cancer, carcinoma of the bladder
Treatment nivolumab 480mg, nivolumab 3mg/kg, ipilimumab 1mg/kg, nivolumab 1mg/kg, ipilimumab 3mg/kg
Clinical Study IdentifierNCT03844256
SponsorAcademisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Bladder Carcinoma or Bladder Disorders or Invasive Bladder Cancer or bladder disorder or urinary tract neoplasm or bladder cancer or Urologic Cancer o...?
Do you have any of these conditions: Bladder Disorders or bladder cancer or Urologic Cancer or Bladder Carcinoma or urinary tract neoplasm or bladder disorder or Invasive Bladder Cancer o...?
Be willing and able to provide written informed consent for the trial
Be 18 years of age on day of signing informed consent
Wish to preserve their bladder function or be ineligible for cystectomy
Must have undergone transurethral biopsy of the bladder tumor, within 35 days of planned treatment commencement. The patient should have a histologically-confirmed diagnosis of muscle-invasive T2-T4a, N0-1M0 urothelial cell carcinoma of the bladder
Must have undergone maximal transurethral resection of the bladder tumour, to an extent that is judged as safe by the urologist performing the resection, within 35 days of planned treatment commencement
Subjects with tumors of mixed urothelial/non-urothelial cell histology are allowed, but urothelial cell carcinoma must be the predominant histology (>50%). Subjects with predominant or exclusively non-urothelial cell histology are not allowed
Have planned for chemoradiotherapy as definitive treatment
Have a performance status of 0 or 1 on the ECOG Performance Scale
Have a bladder function that is accessible for cystoscopical follow up
Demonstrate adequate organ function. All screening labs should be performed within 28 days of registering the patient on the trial
Female participants of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Female participants of childbearing potential should be willing to one highly effective method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 month after the last dose of study medication Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
Male participants should agree to use condoms starting with the first dose of study therapy through 7 month after the last dose of study therapy
Willing to consent to the use of their collected tumor specimen, blood and urine as detailed in the protocol for future scientific research including but not limited to DNA, RNA and protein based biomarker detection

Exclusion Criteria

Has DPD deficiency
Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) urothelial cell carcinoma of the urothelium. Patients who have involvement of the prostatic urethra with urothelial cell cancer may be included if the location can be safely incorporated in the radiation field
Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy
Evidence of distant metastatic disease on a CT or FDG PET/CT chest/abdomen/pelvis performed within 28 days prior to study entry. Up to 3 metastatic lymphnodes in the pelvis (below the common iliac arteries) are allowed, if these can be incorporated in the radiotherapy field
Prior pelvic lymph-adenectomy
Prior pelvic radiotherapy
Has had prior intravenous chemotherapy, targeted small molecule therapy, or radiation therapy for treatment of bladder cancer. Prior intravesical use of BCG and MMC is permissible
Unsuitable for concurrent MMC / capecitabine based ChRT based on pre-existing medical conditions
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy over 10mg daily prednisone (or equivalent) or any other form of immunosuppressive therapy within 14 days prior to registering the patient. Patients with adrenal insufficiency receiving replacement dose steroids are allowed on the trial
Has a known history of active TB (Bacillus Tuberculosis)
Hypersensitivity to nivolumab and/or ipilimumab or any of its excipients
Prior or concurrent known additional malignancy of any site unless disease free for 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA <5)
Has any history of active autoimmune disease, Stevens-Johnson syndrome or Guillain-Barre. Exceptions to this are
Patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone
Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen
Has known history of, or any evidence of active, non-infectious pneumonitis
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has an Human Immunodeficiency Virus (HIV) infection with a PCR detectable viral load
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected)
Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
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