Phase 2b, Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer

Inclusion Criteria

• •To be eligible to participate in this study, patients must:
• •1. Provide written informed consent.
• •2. Have intermediate-risk recurrent superficial TCC of the bladder defined as Stage Ta (low or high grade) or T1 (but with penetration into no more than ½ of the lamina propria), low grade (grade 1 or grade 2), as confirmed by histopathology, and have not recurred within 3-months of a complete course of a prior acceptable therapy (i.e., 6-weekly intravesical administrations of BCG or standard adjuvant treatment with thiotepa, doxorubicin, epirubicin, valrubicin, or mitomycin C).
• •3. Have complete resection of all papillary tumors with the exception of a single superficial papillary tumor that is appropriate to be a marker tumor (\<1 cm in diameter).
• •4. Have ≥ 2 tumor and ≤ 7 tumors visible during cystoscopy and no tumor larger than 3 cm in diameter. If only one tumor is present, it must be large enough to obtain a biopsy specimen adequate to determine the tumor stage and grade and leave a marker tumor.
• •5. Have at least one tumor specimen resected before the start of the study that was positive for H19 expression by ISH. H19 expression positive is defined as \>= 60 % of the tumor cells in the specimen expressing H19 at a moderate staining intensity.
• •6. Have failed at least one prior standard intravesical treatment including chemotherapy with mitomycin C, thiotepa, valrubicin, doxyrubicin, or epirubicin, or immunotherapy with BCG. Failure after treatment with chemotherapy is defined as recurrent disease after at least one intravesical instillation of drug. Failure after treatment with BCG is defined as intolerance to treatment such that treatment was discontinued or after having received 6 or more BCG instillations there is recurrent or persistent disease 3 or more months after initiation of BCG treatment.
• •7. Have a Karnofsky's performance status of greater than or equal to 60%.
• •8. Have adequate bone marrow reserve: Hemoglobin \> 10 g/dL, WBC greater than or equal to 3000/mm3, and platelets \> 100,000 /mm3.
• •9. Have adequate renal function with serum creatinine \< 1.5 x the laboratory upper limit of normal (ULN).
• •10. Have adequate liver function with serum biliru¬bin, AST/SGOT and ALT/SGPT \< 2 times the laboratory ULN.
• •11. Be at least 18 years of age.
• •12. If male, agree to use a condom, if sexually active, and if female, agree to practice one of the acceptable methods of birth control or be surgically sterile or postmenopausal (greater than 1 year post last menstrual cycle.