A Phase I Intravesical PPM Therapy for NMIBC

Exclusion Criteria

• •* 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 6 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 urologic guidelines.
• •* Age 18 years.
• •* Performance status: ECOG performance status of 0, 1, or 2 (Appendix A) or Karnofsky performance status of 50 or higher (Appendix B).
• •* Patient with life expectancy greater than 24 months.
• •* No concurrent radiotherapy, chemotherapy, or other immunotherapy
• •* 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 participating urologist.
• •* Laboratory tests performed within 14 days of study enrollment:
• •Absolute neutrophil count (AGC/ANC) 1,500/uL
• •Platelets 100,000/uL \[Patients may be transfused to meet this requirement\]
• •Hemoglobin 8 g/dL \[Patients may be transfused to meet this requirement\]
• •Calculated glomerular filtration rate (GFR) 50 mL/min/1.73m2
• •Total bilirubin 2.0 X ULN (\< 3 x ULN for patients with Gilbert's syndrome)
• •AST, ALT, ALP 3.0 X ULN
• •* Adequate pulmonary function with no clinical signs of severe pulmonary dysfunction.
• •* Negative serum pregnancy test if the study participant is a female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
• •* Female participants of childbearing potential must adhere to using a medically accepted method of birth control, i.e. a tubal ligation, an approved hormonal contraceptive or an intrauterine device, prior to screening and agree to continue its use during the study and up to 3 months after finishing this study or be surgically sterilized (e.g., hysterectomy or tubal ligation). Males must agree to use barrier methods of birth control while on study.
• •* Provide signed informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations.
• •Patients who meet any of the following criteria will be excluded from study entry.
• •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 (Appendix C), 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 (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 anti-inflammatory 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 nursing.
• •Psychiatric illness/social situations that would limit compliance with study requirements
• •Other illness that in the opinion of the investigator would exclude the patient from participating in this study.
• •Any other malignancy diagnosed within 3 years of trial entry with the exception of:
• •* 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.
• •Patients unwilling to or unable to comply with the protocol.
• •Patients with impaired decision-making capacity.