A Study of Intravesical Apaziquone as a Surgical Adjuvant in Participant Undergoing Transurethral Resection Bladder Tumor (TURBT)
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Apaziquone; Placebo
Intervention description: One dose of apaziquone administered by intravesical administration; Matching placebo (containing 12 mg FD&C red #40, 15 mg sodium chloride, and 10 mg mannitol was supplied in identical appearing vials) by intravesical administration.
Intervention MeSH terms: Apaziquone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bladder Cancer; Non-muscle invasive bladder cancer; Apaziquone; TURBT; Stage Ta, G1-G2

Summary:

      This is a Phase 3, randomized, multicenter, multi-arm, placebo-controlled, double-blind study
      of apaziquone in participants with ≤4 non-muscle invasive bladder cancer (NMIBC), ≤3.5
      centimeters (cm) in diameter, all of which must had been fully resected at TURBT.

      In addition to Screening, participants underwent an assessment of urothelial carcinoma of the
      bladder via cystoscopy for clinically apparent tumor Ta, G1-G2.

      Following TURBT on Day 1, eligible participants were randomized to one of three treatment
      arms in a 1:1:1 ratio.

      Arm 1 : One dose of Apaziquone. Arm 2 : Two Doses of Apaziquone. Arm 3 : Placebo. Primary
      endpoint was to evaluate the Time to Recurrence with either a one instillation of 4 mg
      apaziquone or two instillations of 4 milligram (mg) apaziquone relative to placebo
      instillation following TURBT in a participant with NMIBC who received TURBT.
    

Eligibility criteria:

        1. Participant must have had a diagnosis with urothelial carcinoma of the bladder with
             clinically apparent tumor Ta, G1-G2.

          2. Participant had ≤4 tumors, none of which exceeded 3.5 cm in diameter.

          3. Participant must have been willing to give written informed consent, able to adhere to
             dosing and visit schedules, and meet all study requirements.

          4. Participant was at least 18 years of age at randomization.

          5. Participant must have been willing to practice two forms of contraception, one of
             which must have been a barrier method, from study entry until at least 35 days after
             the last dose of the study drug.

          6. Female participant of childbearing potential must have had a negative pregnancy test
             within 30 days prior to randomization. Female participant who was postmenopausal for
             at least 1 year (defined as more than 12 months since last menses) or were surgically
             sterilized did not require this test.

        Exclusion Criteria:

          1. Participant had an active concurrent malignancy/life-threatening disease. If there was
             a history of prior malignancies/life-threatening diseases, the participant was to be
             disease-free for at least 5 years. Participant with other prior malignancies less than
             5 years before study entry could have still been enrolled if they had received
             treatment resulting in complete resolution of the cancer and currently had no
             clinical, radiologic, or laboratory evidence of active or recurrent disease.

          2. Participant had positive urine cytology for malignancy at Screening.

          3. Participant had an active uncontrolled infection, including a urinary tract infection,
             underlying medical condition, or other serious illness that would impair the ability
             of the participant to receive protocol treatment.

          4. Participant had used any investigational drugs, biologics, or devices within 30 days
             prior to study treatment or planned to use any of these during the course of the
             study.

          5. Participant had any prior intravesical chemotherapy, immunotherapy, or previous
             exposure to apaziquone.

          6. Participant had or has ever had

               -  Upper tract Transitional Cell Carcinoma (TCC).

               -  Urethral tumor (prostatic urethra included).

               -  Any invasive bladder tumor known to be other than tumor Ta, G1-G2.

               -  Any evidence of lymph node or distant metastasis.

               -  Any bladder tumor with histology other than TCC.

               -  Carcinoma in situ (CIS).

          7. Participant had a tumor in a bladder diverticulum.

          8. Participant had received any pelvic radiotherapy (including external beam and/or
             brachytherapy.)

          9. Participant had a bleeding disorder or a screening platelet count <100×10^9/L.

         10. Participant had screening hemoglobin <10 milligrams per deciliter (mg/dL).

         11. Participant had any unstable medical condition that would make it unsafe to undergo
             TURBT.

         12. Participant had a history of interstitial cystitis.

         13. Participant had a history of allergy to red color food dye.

         14. For a participant with a recurrent tumor, the participant had at least a 6-month
             cystoscopically-confirmed tumor-free interval between the last tumor recurrence and
             screening cystoscopic examination.

         15. Participant was pregnant or breast-feeding.