A Phase 1b-2 study of Mitomycin-C / Capecitabine chemoradiotherapy combined with Ipilumimab and Nivolumab or Nivolumab monotherapy as bladder sparing curative treatment for muscle Invasive bladder Cancer: the CRIMI study.
- Conditions
- Muscle invasive bladder cancerT2-4M0 urothelial carcinoma1002765610004994
- Registration Number
- NL-OMON55840
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 50
1 Be willing and able to provide written informed consent for the trial.
2 Be >= 18 years of age on day of signing informed consent.
3 Wish to preserve their bladder function or be ineligible for cystectomy.
4 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.
5 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.
6 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.
7 Have planned for chemoradiotherapy as definitive treatment.
8 Have a performance status of 0 or 1 on the ECOG Performance Scale
9 Have a bladder function that is accessible for cystoscopical follow up.
10 Demonstrate adequate organ function as defined below. All screening labs
should be performed within 28 days of registering the patient on the trial.
11 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.
12 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.
13 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.
14 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.
1 Has DPD deficiency.
2 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.
3 Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative
chemoradiotherapy.
4 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 lymph nodes in the pelvis (below the common iliac arteries) are
allowed, if these can be incorporated in the radiotherapy field.
5 Prior pelvic lymph-adenectomy
6 Prior pelvic radiotherapy
7 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 permittedssible.
8 Unsuitable for concurrent MMC / capecitabine based ChRT based on
pre-existing medical conditions.
9 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. An
exception is fiducials that are aimed at improving positional stability during
the radiotherapy treatment course. These are allowed.
10 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.
11 Has a known history of active TB (Bacillus Tuberculosis)
12 Hypersensitivity to nivolumab and/or ipilimumab or any of its excipients.
13 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)
14 Has any history of active autoimmune disease, Stevens-Johnson syndrome or
Guillain-Barre. Exceptions to this are:
a. Patients with autoimmune-related hypothyroidism on a stable dose of thyroid
replacement hormone
b. Patients with controlled Type I diabetes mellitus on a stable dose of
insulin regimen
15 Has known history of, or any evidence of active, non-infectious
pneumonitis.
16 Has an active infection requiring systemic therapy.
17 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.
18 Has known psychiatric or substance abuse disorders that would interfere
with cooperation with the requirements of the trial.
19 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 do
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Toxicity (CTCAE 4.0) </p><br>
- Secondary Outcome Measures
Name Time Method <p>overall survival (OS)<br /><br>overall survival-rate (OS-rate)<br /><br>response rate (RR) </p><br>