| Eligibility |
Inclusion Criteria:
- Participants must have histologically confirmed MIBC (T2-T4a, N0-N1, M0 per American
Joint Commission on Cancer [AJCC]) pure or mixed histology urothelial carcinoma.
Clinical node- positive (N1) patients are eligible provided the lymph nodes (LNs) are
within the planned surgical LN dissection template.
- The initial TURBT that showed muscularis propria invasion should be within 90 days
prior to beginning study therapy. Participants must have sufficient baseline tumor
tissue from either initial or repeat TURBTs. The local site pathologist will be asked
to estimate and record the rough approximate percentage of viable tumor in the TURBT
sample (initial or repeat TURBT with highest tumor content) to document at least 20%
viable tumor content prior to registration. This is to ensure adequate tissue is
available to perform tumor infiltrating CD8+ T-cell assessment. (The actual CD8+ T
cell analysis will be done by a Central Laboratory and will not be done prior to
registration.)
- Participants must be ineligible for cisplatin-based chemotherapy due to any of the
following:
- Creatinine clearance (CrCl) < 60 mL/min (with ECOG Performance Status (PS) 0-1)
- Hearing impaired = Grade 2 by CTCAE criteria
- Neuropathy = Grade 2 by CTCAE criteria
- Heart failure NYHA = III
- ECOG = 2
- Refusing to undergo cisplatin chemotherapy
- Participants must be medically fit for TURBT and radical cystectomy (RC)
- Age = 18 years
- Ability to understand and willingness to sign IRB-approved informed consent
- Willing to provide tumor tissue, blood, and urine samples for research
- Adequate organ function as measured by the following criteria, obtained = 4 weeks
prior to registration:
- Absolute Neutrophil Count (ANC) = 1000/mm3 (stable off growth factor within 4
weeks of first study drug administration)
- Platelets = 100,000/mm3
- Hemoglobin = 8 g/dL
- Serum Creatinine Clearance = 20 mL/min using the Cockcroft-Gault formula
- ALT and AST = 2.5x ULN
- Total Bilirubin = 1.5x ULN (in the absence of previously diagnosed Gilbert's
disease)
Exclusion Criteria:
- Women who are pregnant or breastfeeding, since the effects of nivolumab and CG0070 on
the fetus or breastfeeding child are unknown. All sexually active females of
childbearing potential (not surgically sterilized and between menarche and 1 year post
menopause) must have a blood test to rule out pregnancy within 4 weeks prior to
registration.
- Participant with local symptoms from bladder cancer, (e.g. gross hematuria, dysuria,
etc.) who are deemed to be unable to complete the treatment protocol.
- Participant with active or prior documented autoimmune disease within the past 2 years
prior to Screening or other immunosuppressive agent within 14 days of study treatment.
NOTE: Participant with well controlled type 1 diabetes mellitus, vitiligo, Graves
disease, Hashimoto's disease, eczema, lichen simplex chronicus, or psoriasis not
requiring systemic treatment (within the past 2 years prior to Screening) are not
excluded
- Participants who have concurrent upper urinary tract (i.e. ureter, renal pelvis)
invasive urothelial carcinoma. Participants with history of non-invasive (Ta, T1, Tis)
upper tract urothelial carcinoma that has been definitively treated with at least one
post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates
no evidence of residual disease are eligible.
- Participants who have another malignancy that could interfere with the evaluation of
safety or efficacy of the study drugs. Participants with a prior malignancy will be
allowed without Principle Investigator approval in the following circumstances:
- Not currently active and diagnosed at least 3 years prior to the date of
registration.
- Non-invasive diseases such as low risk cervical cancer or any cancer in situ.
- Localized (early stage) cancer treated with curative intent (without evidence of
recurrence and intent for further therapy), and in which no chemotherapy was
indicated (e.g. low/intermediate risk prostate cancer, etc.). Participants with
other malignancies not meeting these criteria must be discussed prior to
registration.
- Participants who have received any prior immune checkpoint inhibitor (i.e. anti-KIR,
anti-PD-1, anti- PD-L1, anti-CTLA4 or other).
- Participants who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or
intra-pelvic), open biopsy or significant traumatic injury or specific anti-cancer
treatment = 4 weeks prior to starting study drug, or patients who have had placement
of vascular access device = 1 week prior to starting study drug, or who have not
recovered from side effects of such procedure or injury.
- Participants who have clinically significant cardiac diseases deemed not fit for
radical cystectomy, including any of the following:
- History or presence of serious uncontrolled ventricular arrhythmias.
- Clinically significant resting bradycardia.
- Any of the following within 3 months prior to starting study drug:
severe/unstable angina, Congestive Heart Failure (CHF), Cerebrovascular Accident
(CVA), Transient Ischemic Attack (TIA).
- Uncontrolled hypertension defined by a SBP = 180 mm Hg and/or DBP = 100 mm Hg,
with or without anti-hypertensive medication(s).
- Participants who have history of chronic active liver disease or evidence of acute or
chronic Hepatitis B Virus (HBV) or Hepatitis C (HCV).
- Participants who have known diagnosis of human immunodeficiency virus (HIV) infection.
Testing is not required in absence of clinical suspicion.
- Participants who have known diagnosis of any condition (e.g. post-hematopoietic or
solid organ transplant, pneumonitis, inflammatory bowel disease, etc.) that requires
chronic immunosuppressive therapy which cannot be stopped for the duration of the
clinical trial. Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the
treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of
gout are permitted.
- Participants with any serious and/or uncontrolled concurrent medical conditions (e.g.
active or uncontrolled infection, uncontrolled diabetes) or psychiatric illness that
could, in the investigator's opinion, cause unacceptable safety risks or potentially
interfere with the completion of the treatment according to the protocol.
- Participants who have used any live viral vaccine for prevention of infectious
diseases within 4 weeks prior to study drug(s). Examples of live vaccines include, but
are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken
pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
- Participants unwilling or unable to comply with the protocol.
- Participants with a known allergy to any of the study medications, their analogues, or
excipients in the various formulations of any agent.
- Participants who participate in any other therapeutic clinical trials, including those
with other investigational agents not included in this trial throughout the duration
of this study.
- Use of excluded antiviral medication that cannot be suspended at least 14 days prior
and for 14 days after the administration of any CG0070 treatment throughout the
duration of the trial.
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