Intravesical Administration of rAd-IFN/Syn3 in Patients With BCG-Refractory or Relapsed Bladder Cancer
Condition: Superficial Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: INSTILADRIN
Intervention description: The INSTILADRIN components will be mixed with a diluent. The total dose will be given as a single, one-hour intravesical administration which may, depending on clinical response, be repeated every 3 months up to a maximum of 4 instillations.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Masking description: The participant did not know if they received a high or low dose.
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BCG Refractory or Relapsed Superficial Bladder Cancer; rAd-IFN; Syn3; Intravesical; transitional cell carcinoma of the bladder; superficial non-muscle invasive tumor; Interferon alpha2b; INSTILADRIN

Summary:

      This Phase 2 study is designed to assess the efficacy and safety of INSTILADRIN (rAd-IFN with
      Syn3) when given intravesically to patients with high grade non-muscle invasive bladder
      cancer who are refractory to or have relapsed from BCG therapy. The pharmacodynamics of
      INSTILADRIN will also be studied by measuring the interferon (IFNα2b) levels excreted in the
      urine. rAd-IFN is a non-replicating recombinant adenovirus type 5 (Ad5)-vector encoding the
      interferon alpha-2b (IFNα2b) gene. Syn 3 is clinical surfactant excipient which enhances the
      ability of the adenoviral vector to transfect cells in the bladder wall.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Aged 18 years or older at the time of consent

          2. Able to give informed consent

          3. Subjects with high grade BCG-refractory or relapsed NMIBC including

               -  High grade non-invasive papillary carcinomas (Ta) and subjects with high grade
                  tumors that invade sub-epithelial connective tissue (T1) or

               -  Carcinoma in situ (CIS) only or

               -  CIS and Ta or T1 tumors Refractory is defined as failure to achieve a
                  disease-free state at six months after adequate induction of BCG therapy with
                  either maintenance or re-induction at 3 months. Adequate induction is defined as
                  a minimum of 5 out of 6 induction doses and adequate maintenance is defined as a
                  minimum of 2 out of 3 doses of treatment.

             Relapse is defined as recurrence within 1 year after a complete response to BCG
             treatment

          4. Complete resection of visible papillary lesions or CIS by TURBT or endoscopic
             resection between 14 and 60 days prior to beginning study treatment

          5. Available for the whole duration of the study

          6. Life expectancy >2 years, in the opinion of the investigator

          7. ECOG status 2 or less

          8. Absence of upper tract urothelial carcinoma

          9. Female subjects of childbearing potential must use maximally effective birth control
             during the period of therapy, must be willing to use contraception for 1 month
             following the last study drug infusion and must have a negative urine or serum
             pregnancy test upon entry into this study. Otherwise, female subjects must be
             postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.

         10. Male subjects must be surgically sterile or willing to use a double barrier
             contraception method upon enrollment, during the course of the study, and for 1 month
             following the last study drug infusion.

         11. Adequate laboratory values.

               -  Hemoglobin ≥10 g/dL.

               -  WBC ≥4000/μL.

               -  ANC ≥2000/μL.

               -  Platelet count ≥100,000/μL.

               -  INR within institutional normal limits.

               -  aPTT within institutional normal limits.

               -  AST ≤1.5 x ULN.

               -  ALT ≤1.5 x ULN.

               -  Total bilirubin within institutional normal limits.

               -  Creatinine ≤1.5 x ULN.

        Exclusion Criteria:

          1. Current or previous evidence of muscle invasive or metastatic disease

          2. Current systemic therapy for bladder cancer

          3. Current or prior pelvic external beam radiotherapy

          4. Prior treatment with adenovirus-based drugs

          5. Suspected hypersensitivity to interferon alpha

          6. Existing urinary tract infection or bacterial cystitis

          7. Clinically significant and unexplained elevated liver or renal function tests

          8. Women who are pregnant or lactating

          9. Severe cardiovascular disease

         10. History of malignancy of other organ system within past 5 years (except treated basal
             cell carcinoma or squamous cell carcinoma of the skin)

         11. Subjects who cannot hold instillation for 1 hour

         12. Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation

         13. Intravesical therapy within 6 weeks of enrollment