Phase 2b, Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer
Condition: Superficial Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: BC-819/PEI
Intervention description: Papillary tumors will be resected with the exception of one marker tumor that will remain to examine the effects of the treatment on the remaining tumor. Study treatments will consist of an induction course of six weekly instillations of 20 mg of DTA-H19/PEI into the urinary bladder. Intravesical therapy will be delivered through a Foley catheter. Patients will be instructed to hold the dose in the bladder for two hours after administration. If the patient has a complete response, then she/he will be eligible to receive three additional courses of 3 weekly intravesical administrations of the same dose of investigational product every 12 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bladder Cancer; Refractory; inodiftagene vixteplasmid

Summary:

      This study is designed to assess the efficacy and safety of DTA-H19/PEI given as six
      intravesical instillations of 20 mg of plasmid DNA complexed with PEI into the bladder of
      patients with intermediate risk superficial bladder cancer [recurrent stages Ta (low or high
      grade)and T1, (low grade) transitional cell carcinoma (TCC)] who have failed prior
      intravesical therapies including either Bacillus Calmette-Guérin (BCG) or chemotherapy. The
      primary efficacy objective is to determine the effect of DTA-H19/PEI on the prevention of new
      tumors after the induction course of 6 weekly intravesical administrations of investigational
      product assessed 8 to 10 weeks after the start of treatment. Secondary objectives include
      assessing the ablative effect of DTA-H19/PEI on a marker tumor, safety assessed by the
      incidence and severity of adverse events, determining the long-term (46 weeks) continued
      rates of absence of bladder cancer, and time to tumor recurrence in those patients who had a
      complete response (CR) after the induction course.
    

Eligibility criteria:

        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.

        Exclusion Criteria:

        To be eligible to participate in this study, patients must not:

          1. Have current diagnosis or history of Stage T1 (high grade) or Stage T2 or higher or
             CIS.

          2. Have severe concomitant disease that might limit compliance or completion of the
             protocol.

          3. Have a tumor in a diverticulum, in the prostatic urethra, or covering the ureteral
             orifice.

          4. Have any other malignancy that might impact 5-year survival or might be potentially
             confused with TCC.

          5. Have congenital or acquired immune deficiencies.

          6. Be receiving cytotoxic drugs or corticosteroids.

          7. Have received intravesical therapy within 8 weeks prior to study entry.

          8. Have received radiation therapy for their bladder cancer at any time or any other
             conditions including pelvic irradiation for any condition within 4 months prior to
             study entry.

          9. Have active infections (including urinary tract infections) defined as viral,
             bacterial, or fungal infections requiring therapy, HIV-positive status, concurrent
             febrile illness, or gross hematuria.

         10. Have biopsy, TUR, or traumatic catheterization within 14 days of start of treatment.

         11. If female, be pregnant or breast feeding.

         12. Have participated in any therapeutic research study within the last 8 weeks.

         13. Have participated in any other gene therapy study including patients who have received
             DTA-H19/PEI in the past.