Bladder Cancer
Conditions
Keywords
Bladder Cancer, Non-Muscle Invasive Bladder Cancer, NMIBC, Apaziquone, EOquin, GU Cancer, TURBT
Brief summary
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.
Interventions
DRUGApaziquone
Apaziquone 4 mg in 40 mL diluent
DRUGPlacebo
Placebo for Double Blind Phase
Sponsors
Allergan
Spectrum Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Open Phase Inclusion Criteria: 1. Has the patient given written informed consent and is the patient willing and able to abide by the protocol? 2. Is the patient 18 years old or above? 3. If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception? 4. Does the female patient of childbearing potential have a negative serum pregnancy test at screening? 5. Does the patient with clinically apparent primary or recurrent low grade Ta NMIBC have : * multiple tumors (2-7) * No single Tumor \> 3 cm * No history / evidence of Tis Or does the patient with clinically apparent primary or recurrent high grade Ta NMIBC have: * A single tumor that is ≤ 3 cm * No history / evidence of Tis 6. Is the patient able to retain bladder instillations for a minimum of 60 minutes? 7. Did the patient have upper urinary tract evaluation to exclude urothelial carcinoma, hydronephrosis or renal cell carcinoma or other renal cancers in the 6 months prior to study screening? 8. Is patient's urethra (including prostatic urethra in men) endoscopically free of any visible TCC? 9. For patients with recurrent tumor, did the patient have at least a 6-month cystoscopically-confirmed tumor-free interval between the last tumor recurrence and the time of screening? 10. Has the male patient with a prostate specific antigen (PSA) between 4 and 10 ng/mL had a diagnostic evaluation that reasonably excludes the diagnosis of prostate cancer in the opinion of the Investigator? Double-Blind Phase Inclusion Criteria: 1. Was all visible tumor resected at the initial TURBT? 2. Does Central Pathology review of the patient's bladder tumor confirm: * Low grade Ta disease for multiple tumors (2 - 7) or * High Grade Ta disease for single tumor * No microscopic evidence of lymphovascular invasion and/or evidence of tumor thromboemboli
Exclusion criteria
Open Phase
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recurrence | Recurrence of cancer in the bladder during 24 months of follow-up | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence Rate at 24 Months | 24 months | Measurement the number of participants with the recurrence at 24 months. |
| Participants With Treatment Emergent Adverse Events (TEAEs) | 24 Months from Randomization | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Apaziquone Apaziquone 4 mg in 40 mL diluent
Apaziquone in the Double Blind Phase | 13 |
| Placebo Placebo
Placebo in the Double Blind Phase | 15 |
| Total | 28 |
Baseline characteristics
| Characteristic | Apaziquone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 9 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 13 Participants |
| Age, Continuous | 65.5 years STANDARD_DEVIATION 11.77 | 70.5 years STANDARD_DEVIATION 12.66 | 68.2 years STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 13 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 2 Participants | 2 Participants | 4 Participants |
| Gender Male | 11 Participants | 13 Participants | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 15 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 13 | 12 / 15 |
| serious Total, serious adverse events | 1 / 13 | 1 / 15 |
Outcome results
Primary
Time to Recurrence
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).
Time frame: Recurrence of cancer in the bladder during 24 months of follow-up
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Apaziquone | Time to Recurrence | 9.2 months |
| Placebo | Time to Recurrence | 7.3 months |
Secondary
Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: 24 Months from Randomization
Population: All patients who received Apaziquone in the Open Label Phase and subsequently randomized to one of the treatment arms in the Double Blind Phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apaziquone | Participants With Treatment Emergent Adverse Events (TEAEs) | 11 participants |
| Placebo | Participants With Treatment Emergent Adverse Events (TEAEs) | 12 participants |
Secondary
Recurrence Rate at 24 Months
Measurement the number of participants with the recurrence at 24 months.
Time frame: 24 months
Population: All patients who received Apaziquone in the Open Label Phase and subsequently randomized to one of the treatment arms in the Double Blind Phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apaziquone | Recurrence Rate at 24 Months | 1 participants |
| Placebo | Recurrence Rate at 24 Months | 4 participants |