Bladder CancerPhase 3NCT01410565
Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer
A Phase 3 study testing Apaziquone in people with Bladder Cancer, run by Spectrum Pharmaceuticals, Inc at 47 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Apaziquone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 47 sitesin 2 countries
- Study dates
- Jul 2011to Mar 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Open Phase Inclusion Criteria:
- Has the patient given written informed consent and is the patient willing and able to abide by the protocol?
- Is the patient 18 years old or above?
- If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception?
- Does the female patient of childbearing potential have a negative serum pregnancy test at screening?
- Does the patient with clinically apparent primary or recurrent low grade Ta NMIBC have :
Show all 23Show fewer
- 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
- Is the patient able to retain bladder instillations for a minimum of 60 minutes?
- 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?
- Is patient's urethra (including prostatic urethra in men) endoscopically free of any visible TCC?
- 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?
- 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:
- Was all visible tumor resected at the initial TURBT?
- 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
Who cannot join
- Open Phase Exclusion Criteria:
- Has the patient received any previous pelvic radiotherapy (includes external beam and/or brachytherapy)?
- Has the patient ever received apaziquone?
- Has the patient received an induction course (completed 5 of 6 scheduled weekly instillations) of intravesical BCG (± interferon) with the last dose given less than 12 months ago?
- Has the patient had any prior intravesical chemotherapy, exclusive of single-dose adjuvant intravesical chemotherapy immediately post-TURBT?
- Does the patient have a history of urinary retention or a post void residual ≥ 250 cc by bladder scan or ultrasound (post void residual test may be repeated up to 3 times)?
Show all 25Show fewer
- Does the patient have or has the patient had any bladder tumor with histology other than transitional cell carcinoma?
- Does the patient have or has the patient had micro-papillary transitional cell carcinoma?
- If the patient has recurrent papillary disease of the bladder, has the pathology been anything other than pTa in the past?
- Does the patient have an active urinary tract infection confirmed by culture or a documented history of recurrent UTI (≥ 6 for females and ≥2 for males per year) in the prior 2 years?
- Does the patient have a bleeding disorder or a screening platelet count < 50 x 109/L?
- Does the patient have a screening hemoglobin < 10 mg/dL?
- Does the male patient have a serum PSA > 10 ng/mL?
- Does the patient have a history of Acquired Immunodeficiency Syndrome or HIV positive?
- Does the patient have a condition or a concurrent severe and/or uncontrolled medical or psychiatric disease (e.g., uncontrolled diabetes, decompensated congestive heart failure, myocardial infarction within 6 months of study, unstable and uncontrolled hypertension, or an active uncontrolled infection), which could compromise participation, compliance with scheduled visits and/or completion of the study?
- Has the patient participated in an investigational protocol within the past 90 days?
- Is the patient pregnant or breast feeding?
- Does the patient have a life expectancy of <3 years?
- Has the patient had any other malignancy or received therapy for any malignancy in the last five years except
- non-melanoma skin tumors
- stage 0 (in situ) cervical carcinoma
- undetectable PSA for ≥1 year following definitive therapy for localized prostate cancer?
- Does the patient have documented vesicoureteral reflux or an indwelling ureteral stent?
- Does the patient have tumor in a bladder diverticulum?
- Does the patient have a known allergy to red color food dye?
Trial locations and contacts
47 sites in 2 countries.
47 sites in 2 countries
United States28 sites
Anne Arundel Urology
Annapolis, Maryland, 21401
Urologic Consultants of Southeastern Pennsylvania, LLP
Bala-Cynwyd, Pennsylvania, 19004
Urology Health Specialists
Bryn Mawr, Pennsylvania, 19010
TriState Urologic Services PSC, Inc.
Cincinnati, Ohio, 45212
North Idaho Urology
Coeur d'Alene, Idaho, 83814
The Urology Center of Colorado
Denver, Colorado, 80211
Northeast Indiana Research, LLC
Fort Wayne, Indiana, 46825
Valley Urologic Associates
Glendale, Arizona, 85308
Spectrum Health Medical Group
Grand Rapids, Michigan, 49546
First Urology, PSC
Jeffersonville, Indiana, 47130
South Orange County Medical Research Center
Laguna Woods, California, 92653
Urological Associates of Lancaster
Lancaster, Pennsylvania, 17604
Urology Enterprises
Marietta, Georgia, 30060
Urology Associates of South Texas
McAllen, Texas, 78503
Idaho Urologic Institute, P.A.
Meridian, Idaho, 83642
Connecticut Clinical Research Center
Middlebury, Connecticut, 06762
University of Minnesota
Minneapolis, Minnesota, 55418
Five Valleys Urology
Missoula, Montana, 59802
Integrity Medical Research, LLC
Mountlake Terrace, Washington, 98043
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
University Urology Associates
New York, New York, 10016
Precision Trials, LLC
Phoenix, Arizona, 85032
Urology Associates of Rochester, LLC
Rochester, New York, 14618
Regional Urology, LLC
Shreveport, Louisiana, 71106
Urology of Virginia, PC
Virginia Beach, Virginia, 23454
Urology of Virginia, PLLC
Virginia Beach, Virginia, 23462
Delaware Valley Urology, LLC - Voorhees
Voorhees Township, New Jersey, 08043
Delaware Valley Urology, LLC-Westampton
Woodlane, New Jersey, 08060
Canada19 sites
The Male/Female Health and Research Centre - Royal Court Medical Centre
Barrie, Ontario, L4M7G1
Brantford Urology Research
Brantford, Ontario, N3R4N3
G. Kenneth Jansz Medicine Professional Corporation
Burlington, Ontario, L7N3V2
Urology Resource Centre
Burlington, Ontario, L7S1V2
Queen Elizabeth II Health Science Center
Halifax, Nova Scotia, B3H 1V7
Kingston General Hospital / Queen's University
Kingston, Ontario, K7L3J7
Urology Associates, Urologic Medical Research
Kitchener, Ontario, N2N2B9
Centre universitaire de sante McGill
Montreal, Quebec, H3G1A4
Mor Urology, Inc.
Newmarket, Ontario, L3X1W1
Office of Bernard Goldfarb
North Bay, Ontario, P1B7K8
Stanley Flax Medical Professional Corporation
North York, Ontario, M2J1V1
The Fe/Male Health Centre
Oakville, Ontario, L6H3P1
Urotec
Oshawa, Ontario, L1H7K4
Centre Hospitalier Universitaire de Quebec
Québec, Quebec, G1R3S3
Urology/Male Infertility
Scarborough Village, Ontario, M1S4V5
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec, J1H5N4
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N3M5
University Health Network Princess Margaret Hospital
Toronto, Ontario, M5G2M9
G. Steinhoff Clinical Research Pacific Urologic Research
Victoria, British Columbia, V8V3N1
About this study
Official title: 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)
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.
- Conditions
- Bladder Cancer
- Being tested
- Apaziquone, Placebo
- Keywords
- Bladder Cancer, Non-Muscle Invasive Bladder Cancer, NMIBC, Apaziquone, EOquin, GU Cancer, TURBT
- Medical subject headings
- Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApaziquoneDrug
Also called EO9, EOquin
Apaziquone 4 mg in 40 mL diluent
PlaceboDrug
Placebo for Double Blind Phase
| Study group | Role | What they receive |
|---|---|---|
| Apaziquone | Active comparator | Not described Receives: Drug: Apaziquone |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Recurrence of cancer in the bladder during 24 months of follow-up
Secondary outcomes (2)
Recurrence Rate at 24 Months
Measurement the number of participants with the recurrence at 24 months.
Measured: 24 months
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.
Measured: 24 Months from Randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2011 (estimated)
- Study startJul 2011
- Primary completionMar 2014
- Study completionMar 2014
Why it stopped: Business reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spectrum Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Allergan
- Responsible party
- Sponsor
- Investigators
- Show-Li Sun, MD, Study director, Spectrum Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01410565
- Sponsor's protocol ID
- SPI-1011
- Status last verified
- Dec 2016
- First submitted
- 1 Aug 2011
- Last updated
- 13 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cai T, Nesi G, Tinacci G, Zini E, Mondaini N, Boddi V, Mazzoli S, Bartoletti R. Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study. J Urol. 2008 Jul;180(1):110-5. doi: 10.1016/j.juro.2008.03.038. Epub 2008 May 15.
PubMed 18485394Schellens JH, Planting AS, van Acker BA, Loos WJ, de Boer-Dennert M, van der Burg ME, Koier I, Krediet RT, Stoter G, Verweij J. Phase I and pharmacologic study of the novel indoloquinone bioreductive alkylating cytotoxic drug E09. J Natl Cancer Inst. 1994 Jun 15;86(12):906-12. doi: 10.1093/jnci/86.12.906.
PubMed 8196081Stenzl A, Hennenlotter J, Schilling D. Can we still afford bladder cancer? Curr Opin Urol. 2008 Sep;18(5):488-92. doi: 10.1097/MOU.0b013e32830b8925.
PubMed 18670272
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01410565
- Acronym / sponsor ID
- SPI-1011
- Conditions
- Bladder Cancer
- Keywords
- Bladder Cancer, Non-Muscle Invasive Bladder Cancer, NMIBC, Apaziquone, EOquin, GU Cancer, TURBT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reason
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Spectrum Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Collaborators
- Allergan
- Study start
- Jul 2011
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 5 Aug 2011 (estimated)
- Results
- Posted 13 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apaziquone | Active comparator | Drug: Apaziquone |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Has the patient given written informed consent and is the patient willing and able to abide by the protocol?
- Is the patient 18 years old or above?
- If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception?
- Does the female patient of childbearing potential have a negative serum pregnancy test at screening?
- Does the patient with clinically apparent primary or recurrent low grade Ta NMIBC have :
Key exclusion criteria (25 listed)
- Has the patient received any previous pelvic radiotherapy (includes external beam and/or brachytherapy)?
- Has the patient ever received apaziquone?
- Has the patient received an induction course (completed 5 of 6 scheduled weekly instillations) of intravesical BCG (± interferon) with the last dose given less than 12 months ago?
- Has the patient had any prior intravesical chemotherapy, exclusive of single-dose adjuvant intravesical chemotherapy immediately post-TURBT?
- Does the patient have a history of urinary retention or a post void residual ≥ 250 cc by bladder scan or ultrasound (post void residual test may be repeated up to 3 times)?
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApaziquoneAlso: EO9, EOquinApaziquone 4 mg in 40 mL diluent | Drug | Apaziquone |
| PlaceboPlacebo for Double Blind Phase | Drug | Placebo |
Primary outcome
Time to Recurrence
Time frame: 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).
2 secondary outcomes
Recurrence Rate at 24 Months
Time frame: 24 months
Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: 24 Months from Randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18485394Cai T, Nesi G, Tinacci G, Zini E, Mondaini N, Boddi V, Mazzoli S, Bartoletti R. Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study. J Urol. 2008 Jul;180(1):110-5. doi: 10.1016/j.juro.2008.03.038. Epub 2008 May 15.
- Background: PubMed 8196081Schellens JH, Planting AS, van Acker BA, Loos WJ, de Boer-Dennert M, van der Burg ME, Koier I, Krediet RT, Stoter G, Verweij J. Phase I and pharmacologic study of the novel indoloquinone bioreductive alkylating cytotoxic drug E09. J Natl Cancer Inst. 1994 Jun 15;86(12):906-12. doi: 10.1093/jnci/86.12.906.
- Background: PubMed 18670272Stenzl A, Hennenlotter J, Schilling D. Can we still afford bladder cancer? Curr Opin Urol. 2008 Sep;18(5):488-92. doi: 10.1097/MOU.0b013e32830b8925.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Show-Li Sun, MD study director
Spectrum Pharmaceuticals, Inc
47 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apaziquone in people with Bladder Cancer, run by Spectrum Pharmaceuticals, Inc at 47 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Recurrence (time frame: Recurrence of cancer in the bladder during 24 months of follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01410565, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2016.