A Study of Intravesical Apaziquone as a Surgical Adjuvant in Participant Undergoing Transurethral Resection Bladder Tumor (TURBT)

NCT ID: NCT02563561

Last Updated: 2021-10-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-09
• Study Completion Date: 2017-03-10

Brief 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.

Detailed Description

This is a Phase 3, randomized, multicenter, multi-arm, placebo-controlled, double-blind study of apaziquone in participants with ≤4 non-muscle invasive bladder tumors, ≤3.5 cm in diameter, all of which must have 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:

• Day 1: administration of 4 mg of apaziquone 60±30 minutes post-TURBT
• Day 15 (±5 days): administration of placebo

Arm 2 : Two Doses of Apaziquone :

• Day 1: administration of 4 mg of apaziquone 60±30 minutes post-TURBT
• Day 15 (±5 days): administration of 4 mg of apaziquone

Arm 3: Placebo :

• Day 1 : administration of placebo 60±30 minutes post-TURBT
• Day 15 (±5 days) : administration of placebo

Once randomized, Day 1 study drug instillation occurred 60 ±30 minutes post TURBT. Participants returned on Day 15 (±5 days) for a second instillation unless their pathology results showed non Ta, G1-G2 histology; in the absence of local pathology results by the Day 15 visit, participants received a second instillation of study drug. All histology specimens were reviewed by a local pathology laboratory and all clinical treatment decisions and study analyses were based on the local pathology review. Participants whose pathology was other than Ta, G1-G2 were followed for safety at Day 35 (±5 days) from the last dose of study drug and then discontinued from the study.

Participants with pathology confirmed Ta, G1-G2 disease were followed according to the schedule below :

• Cystoscopic examination and urine cytology every 90 days (±10 days) (calculated from date of TURBT) through 24 months for tumor recurrence and progression.
• If at any time during the 24 months follow up period there was a tumor recurrence, the participant continued on study with follow-up cystoscopic examination and urine cytology every 90 days (±10 days) (calculated from date of TURBT) through the end of 24 months. Participants with a recurrence were permitted to have a follow-up TURBT.
• If at any time during the 24 months follow up period there was a tumor recurrence and/or participant started on another therapy, the participant was followed by telephone, for safety every 90 days (±10 days) (calculated from date of TURBT) through the end of 24 months.

Duration of Study: The duration of the study for each participant was approximately 24 months including:

• Screening Period : 30-days
• Treatment Period : Day 1 and Day 15 (±5 days)
• Safety and Follow-up Period: 24-months

Conditions

Bladder Cancer

Keywords

Bladder Cancer; Non-muscle invasive bladder cancer; Apaziquone; TURBT; Stage Ta, G1-G2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1 Dose Apaziquone

Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post transurethral resection of bladder tumor (TURBT) on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).

Group Type: EXPERIMENTAL

Apaziquone

Intervention Type: DRUG

One dose of apaziquone administered by intravesical administration

Placebo

Intervention Type: OTHER

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.

2 Dose Apaziquone

Participants were randomized to receive first dose of 4 mg of apaziquone by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of 4 mg of apaziquone by intravesical administration via an indwelling catheter on Day 15 (±5 days).

Group Type: EXPERIMENTAL

Apaziquone

Intervention Type: DRUG

One dose of apaziquone administered by intravesical administration

Placebo

Participants were randomized to receive first dose of matching placebo by intravesical administration into the bladder at 60 ± 30 minutes post TURBT on Day 1 via an indwelling 100% Silicone Foley catheter. Followed by second dose of matching placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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.

Interventions

Apaziquone

One dose of apaziquone administered by intravesical administration

Intervention Type: DRUG

Placebo

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 Type: OTHER

Other Intervention Names

EOquin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Urology Center of Colorado

Denver, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SPI-EOQ-13-305

Identifier Type: -

Identifier Source: org_study_id