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Apaziquone

6 weekly multi-instillation of Apaziquone 4 mg in 40 mL

6 weekly multi-instillation of matching placebo in 40mL

Placebo

Show-Li Sun, MD

This is an international, multicenter, double-blind, placebo-controlled, randomized study. All eligible patients entering the open label phase of the study will receive a single immediate instillation of apaziquone (4 mg in 40 mL diluent), post transurethral resection-bladder tumor (TURBT). Following Central Pathology review of histology and Double Blind Phase qualification, patients with confirmed eligibility will be randomized to receive either 6 weekly intravesical instillations of apaziquone or matching placebo and undergo cystoscopic and safety assessments every 3 months for 24 months. Patients with histologic evidence of recurrent disease during the study will be treated according to current treatment guidelines or local standard of care. Safety and efficacy assessments will be performed at 3 month intervals for all randomized patients throughout the study. Patients who receive single dose of apaziquone immediately following TURBT and are not eligible for randomization will be followed for 3 months by cystoscopic exam and safety assessments.

Efficacy and Safety Study of Apaziquone vs. Placebo in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC)

A Phase 3 International, Double-Bind Trial Evaluating Efficacy and Safety of Multiple Instillations of Intravesical Apaziquone vs. Placebo in Patients With Low-Intermediate Risk Non-Muscle Invasive Bladder Cancer (NMIBC)

Time from randomization to the date of first histologically confirmed recurrence of bladder cancer

Proportion of patients with recurrence at or before 24 months

Allergan

Spectrum Pharmaceuticals, Inc

6 weekly multi-instillation of matching placebo in 40 mL

Open Label-Apaziquone

Apaziquone (4 mg in 40 mL)

Apaziquone: 6 weekly multi-instillation of Apaziquone 4 mg in 40 mL

Matching placebo (40 mL)

Placebo: 6 weekly multi-instillation of matching placebo in 40mL

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Gajanan Bhat, PhD

Patients who were in the Double Blind Phase

Time to Recurrence

2-Year Recurrence Rate

Open Label Phase

Double Blind Phase

Natriuretic Agents

Mannitol

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).

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).

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).

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.

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.

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

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

A Multicenter, Multi-Arm, Randomized, Multi-Dose, Placebo-Controlled, Double-Blind, Phase 3 Study of Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant in the Immediate Postoperative Period in Patients Undergoing Transurethral Resection for Non- Muscle Invasive Bladder Cancer

Time from randomization to the date of histologically confirmed recurrence of bladder cancer. A recurrence was defined as any pathologically confirmed disease of ≥Ta tumor histology or carcinoma in situ (CIS) post-treatment.

The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before Year 2. A recurrence was defined as any pathologically confirmed disease of ≥Ta tumor histology or CIS post-treatment.

The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before Year 1. A recurrence was defined as any pathologically confirmed disease of ≥Ta tumor histology or CIS post-treatment.

Time to disease progression was defined as the time from randomization to the first disease progression. The development of T2 or greater disease was only included in the assessment of time to disease progression.

An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. TEAEs were adverse events that occurred from the first dose of study treatment until 40 days after the last dose of study drug administration or 40 days after the date of participant early discontinuation. Treatment-related AEs included TEAEs with relationship to study treatment reported as possible, probable, definite, or missing. An SAE was an AE resulting in any of the outcomes: death; initial/prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly.

Safety Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.

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 placebo by intravesical administration via an indwelling catheter on Day 15 (±5 days).

1 Dose Apaziquone

2 Dose Apaziquone

The study was terminated as per Sponsor's decision.

Shanta Chawla

Data for this outcome measure was not collected due to early termination of study.

1-Year Recurrence Rate

Time to Progression

TEAEs

Treatment-Related AEs

SAEs

TEAEs Leading to Discontinuation

Death

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and Death

Overall Study

This is an international, multicenter, double-blind, placebo-controlled, randomized study. All eligible patients entering the open label phase of the study will receive a single immediate instillation of apaziquone (4 mg in 40 mL diluent), post transurethral resection-bladder tumor (TURBT). Following Central Pathology review of histology and Double Blind Phase qualification, patients with confirmed eligibility will be randomized to receive either 6 weekly intravesical instillations of apaziquone or matching placebo and undergo cystoscopic and safety assessments every 3 months for 24 months from randomization. Patients with histologic evidence of recurrent disease during the study will be treated according to current treatment guidelines or local standard of care. Safety and efficacy assessments will be performed at 3 month intervals for all randomized patients throughout the study. Patients who receive single dose of apaziquone immediately following TURBT and are not eligible for randomization will be followed for 3 months by cystoscopic exam and safety assessments.

Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer

A Phase 3 International, Multicenter, Double-Blind, Placebo-Controlled, Randomized Trial Evaluating the Efficacy and Safety of Multiple Instillations of Intravesical Apaziquone vs. Placebo in Patients With Low-Intermediate Risk Non-Muscle Invasive Bladder Cancer (NMIBC)

Time to recurrence is the time from randomization to the date of first histologically confirmed recurrence of bladder cancer (for eligible patients with Low- intermediate risk NMIBC, who had undergone TURBT followed by, a single instillation of apaziquone immediately post TURBT and multiple instillations of apaziquone or placebo).

Measurement the number of participants with the recurrence at 24 months.

TEAEs will be mainly characterized by the number of treatment emergent adverse events and treatment related AEs that occur or worsen after the first dose of study treatment.

Apaziquone: Apaziquone 4 mg in 40 mL diluent

Apaziquone: Apaziquone in the Double Blind Phase

Placebo

Placebo: Placebo in the Double Blind Phase

Apaziquone 4 mg in 40 mL diluent

Apaziquone in the Double Blind Phase

Placebo

Placebo in the Double Blind Phase

Gender

Safety Analysis Population included all randomized patients in the double blind phase.

Gajanan Bhat

Apaziquone: Apaziquone 4 mg in 40 mL diluent

Apaziquone in the Double Blind Phase

All patients who received Apaziquone in the Open Label Phase and subsequently randomized to one of the treatment arms in the Double Blind Phase. Participants without recurrence were censored.

All patients who received Apaziquone in the Open Label Phase and subsequently randomized to one of the treatment arms in the Double Blind Phase.

Recurrence Rate at 24 Months

Participants With Treatment Emergent Adverse Events (TEAEs)

Open Label Phase Apaziquone

immediate instillation after TURBT + 6 weekly instillation 4mg/mL Apaziquone

EO9(Apaziquone)

The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of intravesical instillation of EO9 in patients with non-muscle invasive bladder cancer (NMIBC).

Safety and Pharmacokinetic Study of EO9(Intravesical Instillation)

Phase I Clinical Trial to Evaluate the Safety and Pharmacokinetics of Intravesical Instillation of EO9 in Patients With Non-muscle Invasive Bladder Cancer(NMIBC)

Handok Inc.

4 mg/40 mL, Intravesical instillation, Single dose within 6 hours after TURBT

EO9 (Apaziquone)

40 mL, Intravesical instillation, Single dose within 6 hours after TURBT

Yoshihiro Nambu, M.D., Ph.D.

Woo Ick Jang, M.D., Ph.D.

The purpose of this study is to evaluate the efficacy and safety in patients with non-muscle invasive bladder cancer histologically diagnosed to be stage Ta and G1 or G2 and who were randomized into either an EO9 or placebo group after TURBT.

Single Immediate Instillation of EO9 After TURBT in Patients With Non-muscle-invasive Bladder Cancer (NMIBC)

Randomized, Placebo-controlled, Double-blinded Study of Single Immediate Instillation of EO9 After TURBT in Patients With NMIBC

Nippon Kayaku Co., Ltd.

TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT

TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT

A single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT

A single intravesical dose of placebo instilled into the bladder post-TURBT

TransUrethral Resection of the Bladder Tumor

TURBT

Shanta Chawla, MD

The purpose of this study was to evaluate the 2-Year Recurrence Rate of bladder cancer in randomized patients with tumor histology Ta, G1-G2 who received TransUrethral Resection of Bladder Tumor (TURBT) plus apaziquone versus those who received TURBT plus placebo.

This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study. Within 14 days of Screening, eligible patients underwent a TURBT during Visit 1 (Day 0) following which they were immediately randomized in a 1:1 ratio to receive either placebo or 4 mg apaziquone, instilled in a volume of 40 mL into the bladder within 6 hours from the end of the TURBT procedure. After a 60-minute retention period, study drug was drained from the bladder.

A postoperative follow-up examination and review of the local pathology report were performed at Visit 2, which occurred 21 days (±10 days) after the TURBT (Week 3).

* If the histology of the patient's tumor was confirmed as Ta, G1-G2 (ie, low grade according to World Health Organization \[WHO\]/International Society of Urologic Pathology \[ISUP\] classification), no further treatment was given and the patient was observed cystoscopically every 3 months through Year 2 for tumor recurrence (Visit 3 through Visit 10).
* If the histology of the patient's tumor was other than Ta, G1 or G2 (low grade \[WHO/ISUP classification\]), further treatment was given in accordance with current treatment guidelines, and the patient was followed up cystoscopically every 3 months through Year 2 for tumor recurrence (Visit 3 through Visit 10).

All patients were to be followed for 2 years.

Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-612)

A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial of Single-Dose Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant Instilled in the Early Postoperative Period in Patients Undergoing Transurethral Resection for Noninvasive Bladder Cancer (Protocol SPI-612)

The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before year 2.

The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor.

The percentage of participants that progress to either a higher stage or grade from the histologically confirmed stage and grade at time of randomization.

The number of months from randomization to progression to either a higher stage or grade of the patient's bladder tumor.

The number of histologically confirmed recurrences during the course of the study.

The number of months from randomization to histologically confirmed progression of the patient's bladder tumor or death from any cause

The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor or death from any cause

The number of months from randomization to death from any cause.

Apaziquone: TURBT + a single intravesical dose of EOquin® 4mg in 40ml instilled into the bladder post-TURBT

Placebo: TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT

Apaziquone: TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT

65-75

Age, Customized

Canada

United States

Poland

Region of Enrollment

Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.

Recurrence Rate at 2 Years

Progression Rate at 2 Years

Number of Recurrences Per Patient

Disease-Free Interval

Disease-Free Survival

Overall Survival

Carcinoma in Situ

Apaziquone (EOquinTM) 4 mg/40 mL was administered by intravesical instillation once a week for 6 consecutive weeks.

In addition, patients with CIS were to receive further maintenance therapy of 3 weekly apaziquone (EOquinTM) instillations at 3, 6, and 12 months from the date of histological diagnosis.

Alfred Witjes, MD, Prof.

Kees Hendricksen, MD

A non-randomized, open-label phase II study to explore the feasibility, time to recurrence, duration of response and safety of the adjuvant intravesical instillation of EOquin (apaziquone) in patients with high-risk superficial bladder tumors, and the response and duration of response in patients with carcinoma in situ of the bladder.

Endpoints: Time to recurrence, duration of response and safety

Number of Patients: 53 patients

Study Design: Non-randomized, open-label study.

Key Inclusion Criteria: High-risk patients according to EAU criteria defined as

* pT1 and/or Grade 2b-3, or multiple and highly recurrent
* histologically confirmed carcinoma in situ (CIS)

Key Exclusion Criteria:

pTa Grade 1 or pT1 Grade 1 tumors, existing urinary tract infection or recurrent severe bacterial cystitis; those who cannot tolerate intravesical administration or intravesical surgical manipulation due to the presence of concomitant serious illness; no prior intravesical chemotherapy or immunotherapy in the last three months; no prior EOquin treatment (intravenous or intravesical) in last 12 months.

Study Treatment:

All patients will receive intravesical instillation of EOquin™ 4-mg/40 mL instillate once a week for six consecutive weeks

Patient with carcinoma in situ (CIS) will receive further maintenance therapy with 3 consecutive weekly EOquin instillations at the following time points: 3, 6, 12, 18, and 24 months from the date of TUR. At 3-month follow up visit patients will undergo cystoscopic bladder biopsy and urine cytology. If bladder biopsy is negative at 3-month visit, the follow up during the remaining visits will be by cystoscopy and urine cytology only, which will be done prior to the start of maintenance therapy. In case of positive cytology presence of CIS has to be confirmed histologically with biopsies.

At 6 months follow-up, if biopsies are positive for CIS, no further maintenance therapy will be given; patient will be taken off-study.

Duration of Patient Participation:

Intravesical instillation of EOquin™ will be given once a week for six consecutive weeks. All patients will have follow-up evaluations carried out at 3, 6, 9, 12, 15 and 18 months from the TUR date or until progressive disease is observed. In case of recurrence, patients will go off the study and further treatment will be at the investigator's discretion.

Off Study:

Patients will be taken off the study:

* Upon first recurrence and or progression
* Persistent CIS at 6 months follow up
* Recurrent CIS after biopsy proven complete response

Phase II Trial of EOquin in High-risk Superficial Bladder Cancer

Phase II Study of Intravesical Instillation of EOQUIN™ in High Risk Superficial Bladder Cancer

Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-611)

A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial of Single Dose Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant Instilled in the Early Postoperative Period in Patients Undergoing Transurethral Resection for Noninvasive Bladder Cancer (Protocol SPI-611)

Spots Global Cancer Trial Database for apaziquone

Every month we try and update this database with for apaziquone cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety Study of Apaziquone vs. Placebo in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC)	NCT01469221	Bladder Cancer	Apaziquone Placebo	18 Years -	Spectrum Pharmaceuticals, Inc
A Study of Intravesical Apaziquone as a Surgical Adjuvant in Participant Undergoing Transurethral Resection Bladder Tumor (TURBT)	NCT02563561	Bladder Cancer	Apaziquone Placebo	18 Years -	Spectrum Pharmaceuticals, Inc
Efficacy and Safety Study of Apaziquone vs. Placebo in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC)	NCT01469221	Bladder Cancer	Apaziquone Placebo	18 Years -	Spectrum Pharmaceuticals, Inc
Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer	NCT01410565	Bladder Cancer	Apaziquone Placebo	18 Years -	Spectrum Pharmaceuticals, Inc
Safety and Pharmacokinetic Study of EO9(Intravesical Instillation)	NCT01373398	Bladder Cancer	EO9(Apaziquone)	20 Years - 74 Years	Handok Inc.
Single Immediate Instillation of EO9 After TURBT in Patients With Non-muscle-invasive Bladder Cancer (NMIBC)	NCT01475266	Bladder Cancer	EO9 (Apaziquone... Placebo	20 Years -	Nippon Kayaku Co., Ltd.
Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer	NCT01410565	Bladder Cancer	Apaziquone Placebo	18 Years -	Spectrum Pharmaceuticals, Inc
Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-612)	NCT00598806	Bladder Cancer	Apaziquone Placebo TURBT	18 Years -	Spectrum Pharmaceuticals, Inc
Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-612)	NCT00598806	Bladder Cancer	Apaziquone Placebo TURBT	18 Years -	Spectrum Pharmaceuticals, Inc
Phase II Trial of EOquin in High-risk Superficial Bladder Cancer	NCT00141531	Bladder Neoplas...	Apaziquone	18 Years -	Spectrum Pharmaceuticals, Inc
Single Immediate Instillation of EO9 After TURBT in Patients With Non-muscle-invasive Bladder Cancer (NMIBC)	NCT01475266	Bladder Cancer	EO9 (Apaziquone... Placebo	20 Years -	Nippon Kayaku Co., Ltd.
Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-611)	NCT00461591	Bladder Cancer	Apaziquone Placebo TURBT	18 Years -	Spectrum Pharmaceuticals, Inc
Safety and Pharmacokinetic Study of EO9(Intravesical Instillation)	NCT01373398	Bladder Cancer	EO9(Apaziquone)	20 Years - 74 Years	Handok Inc.

Spots Global Cancer Trial Database for apaziquone

Every month we try and update this database with for apaziquone cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for apaziquone cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.