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

Bladder Cancer Clinical Trial

Official title: A Randomized, Multicenter, Two-Arm, Single-Dose, Double-Blind, Placebo-CONtrolled Phase 3 Study of Intravesical Qapzola™ (Apaziquone) as a Chemotherapy Adjuvant to TransUrEthral Resection of Bladder Tumors in Patients With Low- to Intermediate-Risk Non-Muscle Invasive Bladder Cancer (CONQUER)

Status Terminated

Clinical Trial Summary

This is a randomized, multicenter, two-arm, double-blind, placebo-controlled study of Qapzola in participants with low- to intermediate-risk non-muscle invasive bladder cancer (NMIBC), assessed according to the 2016 American Urology Association (AUA) Guidelines. Specifically, only participants with the following low-to intermediate-risk tumor characteristics were included in the study.

2016 American Urological Association Stratification for Non-Muscle Invasive Bladder Cancer:

Low Risk

• Low grade solitary Ta ≤3 centimeters (cm)

• Papillary urothelial neoplasm of low malignant potential (PUNLMP)

Intermediate Risk

• Recurrence within 1 year, low-grade Ta

• Solitary low-grade Ta >3 cm

• Low-grade Ta, multifocal

• High-grade Ta, ≤3 cm (solitary tumor)

Clinical Trial Description

In addition to other Screening assessments, participants underwent an assessment of urothelial carcinoma of the bladder via cystoscopy for clinically apparent tumor of Ta histology, including PUNLMP, although participants with strongly suspected PUNLMP at Screening or transurethral resection of bladder tumor (TURBT) were not to be enrolled in the study. The qualifying cystoscopy could be performed up to 45 days prior to signing the informed consent.

Eligible participants were randomized in a 2:1 ratio to either:

• Arm 1: One dose of 8 milligrams (mg) Qapzola

• Arm 2: One dose of placebo

Once approved for randomization, participants underwent TURBT on Day 1 and the study drug instillation occurred at 60 ± 30 minutes post-TURBT and was retained for 60 minutes (±5 minutes) in the bladder. All histology specimens were reviewed by a local pathology laboratory and all clinical treatment decisions were based on the local pathology review. Participant target disease was confirmed and efficacy analyses were performed based on the pathology results. The target study population was low- to intermediate-risk participants who had Ta histology, including PUNLMP, as confirmed by a pathology laboratory. Participants with strongly suspected PUNLMP at Screening or TURBT were not to be enrolled in the study. Participants whose tumor histology did not meet the criteria for eligibility, as confirmed by pathology (Non-Target Population), were to be followed up for safety on Day 35 (±5 days) (Safety Follow-up Visit) and were discontinued from the study. If the pathology results were delayed beyond 35 days, the Safety Follow-up Visit was to be conducted when the results were available for these participants.

Participants who had pathology-confirmed target histology did not receive additional medications to treat NMIBC during the follow-up while on the study. All target disease participants were to be followed until either a confirmed tumor recurrence, additional bladder cancer treatments, or until the End-of-Study, whichever occurred first.

The primary analysis was conducted once the required number of recurrence events were observed. A recurrence was defined as any pathologically confirmed disease of ≥Ta histology or carcinoma in situ (CIS) post-treatment. The number of events needed to perform the final primary endpoint analysis was estimated based on the recurrence rate at 24 months from previous studies. The follow-up schedule is below:

• Cystoscopic examination (all participants) and urine cytology (only participants with a Baseline diagnosis of intermediate-risk NMIBC) every 3 months (±30 days) (calculated from date of TURBT) for 2 years for tumor recurrence and progression and then every 6 months (±60 days) until either a confirmed tumor recurrence or the End-of-Study, whichever occurred first.

• If at any time during the study there was a histologically confirmed tumor recurrence, the participants discontinued from the study at that time and could then be treated per the Investigator's standard of care.

The study was to end (End-of-Study) when the required number of events for the primary endpoint analysis was accrued.

Duration of Study: The duration of the study for each participant was as follows:

• Screening Period: up to 30 days

• Treatment: Day 1

• Safety Follow-up: Day 35 (±5 days) after treatment

• Follow-up Period: No follow-up in non-Target Population. Until either a confirmed tumor recurrence or the End-of-Study, whichever occurred first in the Target Population. ;

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

• NCT number: NCT03224182
• Study type: Interventional
• Source: Spectrum Pharmaceuticals, Inc
• Status: Terminated
• Phase: Phase 3
• Start date: August 4, 2017
• Completion date: September 26, 2019