| Eligibility |
Inclusion Criteria:
- Histologically confirmed non muscle invasive bladder cancer (NMIBC), defined as
noninvasive papillary carcinoma (Ta), carcinoma in situ (CIS) or carcinoma invading
the subepithelial connective tissue (T1), determined via transurethral resection of
bladder tumor (TURBT) within 3 months of enrollment
- Participant must have Bacillus Calmette Guerin (BCG)-unresponsive NMIBC or intolerance
of treatment with BCG. BCG-unresponsive disease is defined as being at least one of
the following:
- Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary
disease/tumor invades the subepithelial connective tissue) disease within 12
months of completion of adequate BCG therapy
- Recurrent high-grade Ta/T1 disease within 12 months of completion of adequate BCG
therapy
- T1 high-grade disease at the first evaluation following an induction BCG course.
In this context, adequate BCG therapy is defined as at least one of the
following:
- At least five of six doses of an initial induction course plus at least two
of three doses of maintenance therapy
- At least five of six doses of an initial induction course plus at least two
of six doses of a second induction course
- Refuse or intolerant of a radical cystectomy recommended by the treating urologist as
the standard next therapy per American Urological Association (AUA) guideline
- Age = 18 years at time of consent
- Performance status: Eastern Cooperative Oncology Group (ECOG) performance status of 0,
1, or 2
- Patient with life expectancy greater than 24 months
- No concurrent radiotherapy, chemotherapy, or other immunotherapy for bladder cancer.
No BCG or other intravesical treatment within 4 weeks
- No scheduled radiotherapy, chemotherapy, other immunotherapy, or surgery before the
scheduled response evaluation
- Recovery from prior treatment side effects that might interfere with the study
treatment, in the judgment of the investigator
- Absolute neutrophil count (absolute granulocyte count [AGC]/absolute neutrophil count
[ANC]) = 1,500/µL
- Platelets = 100,000/µL (Patients may be transfused to meet this requirement)
- Hemoglobin = 8 g/dL (Patients may be transfused to meet this requirement)
- Calculated glomerular filtration rate (GFR) = 30 mL/min
- Total bilirubin = 2.0 × institutional upper limit of normal (ULN) (< 3 × ULN for
patients with Gilbert's syndrome)
- Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) =
3.0 × institutional ULN
- Adequate pulmonary function by clinical assessment with no clinical signs of severe
pulmonary dysfunction
- Participants of childbearing potential must agree to using adequate contraception
(e.g., hormonal or barrier method of birth control; abstinence, an intrauterine
device) for the duration of study participation (including dosing interruptions) and
up to 3 months after last study treatment; or be surgically sterilized (e.g.,
hysterectomy, tubal ligation, or vasectomy)
- Ability to understand and willingness to sign an informed consent form
- Ability and willingness to adhere to the study visit schedule and other protocol
requirements
Exclusion Criteria:
- Existence of cancer at the upper urinary tract
- Concurrent use of other investigational agents
- Evidence of regional and/or distant metastasis
- NYHA (New York Heart Association) class III or IV heart failure, uncontrollable
supraventricular arrhythmias, any history of a ventricular arrhythmia, or other
clinical signs of severe cardiac dysfunction
- Symptomatic congestive heart failure (CHF), severe/unstable angina pectoris, or
myocardial infarction within 6 months prior to study entry
- Patient has an intractable bleeding disorder (e.g., coagulation factors deficiencies,
Von Willebrand Disease)
- Patient taking medications that affect coagulation, such as aspirin (though, aspirin
81 mg oral once daily is allowed), Coumadin/Warfarin, heparin, low molecular weight
heparin, direct thrombin inhibitors, and direct factor Xa inhibitors. Other
nonsteroidal antiinflammatory drugs (NSAIDs) are allowed as long as they are
discontinued the day before therapy
- History or evidence of uncontrollable central nervous system (CNS) disease
- Active systemic infection requiring parenteral antibiotic therapy
- Women who are pregnant or breast feeding
- Any other malignancy diagnosed within 3 years of trial entry with the exception of the
following:
- Basal or squamous cell skin cancers, or
- Noninvasive cancer of the cervix, or
- Any other cancer deemed to be of low-risk for progression or patient morbidity
during trial period, such as localized prostate cancer after definitive treatment
and prostate-specific antigen (PSA) less than 0.2 ng/mL
- Any condition that would prohibit the understanding or rendering of informed consent
- Any condition that in the opinion of the investigator would interfere with the
participant's safety or compliance while on trial
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