Superficial Bladder CancerPhase 2NCT01687244
Intravesical Administration of rAd-IFN/Syn3 in Patients With BCG-Refractory or Relapsed Bladder Cancer
A Phase 2 study testing INSTILADRIN in people with Superficial Bladder Cancer, run by FKD Therapies Oy.
Trial summary
This Phase 2 study is designed to assess the efficacy and safety of INSTILADRIN (rAd-IFN with Syn3) when given intravesically to patients with high grade non-muscle invasive bladder cancer who are refractory to or have relapsed from BCG therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Superficial Bladder Cancer
- What is being tested?
- INSTILADRIN
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Sep 2012to Jan 2016
- Phase
- Phase 2
- 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
- Aged 18 years or older at the time of consent
- Able to give informed consent
- Subjects with high grade BCG-refractory or relapsed NMIBC including
- High grade non-invasive papillary carcinomas (Ta) and subjects with high grade tumors that invade sub-epithelial connective tissue (T1) or
- Carcinoma in situ (CIS) only or
- CIS and Ta or T1 tumors Refractory is defined as failure to achieve a disease-free state at six months after adequate induction of BCG therapy with either maintenance or re-induction at 3 months. Adequate induction is defined as a minimum of 5 out of 6 induction doses and adequate maintenance is defined as a minimum of 2 out of 3 doses of treatment.
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- Relapse is defined as recurrence within 1 year after a complete response to BCG treatment
- Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment
- Available for the whole duration of the study
- Life expectancy >2 years, in the opinion of the investigator
- ECOG status 2 or less
- Absence of upper tract urothelial carcinoma
- Female subjects of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last study drug infusion and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
- Male subjects must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion.
- Adequate laboratory values.
- Hemoglobin ≥10 g/dL.
- WBC ≥4000/μL.
- ANC ≥2000/μL.
- Platelet count ≥100,000/μL.
- INR within institutional normal limits.
- aPTT within institutional normal limits.
- AST ≤1.5 x ULN.
- ALT ≤1.5 x ULN.
- Total bilirubin within institutional normal limits.
- Creatinine ≤1.5 x ULN.
Who cannot join
- Current or previous evidence of muscle invasive or metastatic disease
- Current systemic therapy for bladder cancer
- Current or prior pelvic external beam radiotherapy
- Prior treatment with adenovirus-based drugs
- Suspected hypersensitivity to interferon alpha
- Existing urinary tract infection or bacterial cystitis
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- Clinically significant and unexplained elevated liver or renal function tests
- Women who are pregnant or lactating
- Severe cardiovascular disease
- History of malignancy of other organ system within past 5 years (except treated basal cell carcinoma or squamous cell carcinoma of the skin)
- Subjects who cannot hold instillation for 1 hour
- Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation
- Intravesical therapy within 6 weeks of enrollment
About this study
Official title: A Phase 2, Randomized, Open Label, Parallel Arm Study to Evaluate the Safety and Efficacy of rAd-IFN/Syn3 Following Intravesical Administration in Subjects With High Grade, BCG Refractory or Relapsed Superficial Bladder Cancer
This Phase 2 study is designed to assess the efficacy and safety of INSTILADRIN (rAd-IFN with Syn3) when given intravesically to patients with high grade non-muscle invasive bladder cancer who are refractory to or have relapsed from BCG therapy. The pharmacodynamics of INSTILADRIN will also be studied by measuring the interferon (IFNα2b) levels excreted in the urine. rAd-IFN is a non-replicating recombinant adenovirus type 5 (Ad5)-vector encoding the interferon alpha-2b (IFNα2b) gene. Syn 3 is clinical surfactant excipient which enhances the ability of the adenoviral vector to transfect cells in the bladder wall.
Read the detailed description
Criteria for Evaluation:
Efficacy: A Response is defined as no evidence of recurrence of a high grade tumor by cystoscopy, cytology or if clinically indicated, biopsy.
Safety: The safety and tolerability of INSTILADRIN will be evaluated based on adverse event reports, vital signs, ECGs, clinical laboratory values and results of physical examination.
- Conditions
- Superficial Bladder Cancer
- Being tested
- INSTILADRIN
- Keywords
- BCG Refractory or Relapsed Superficial Bladder Cancer, rAd-IFN, Syn3, Intravesical, transitional cell carcinoma of the bladder, superficial non-muscle invasive tumor, Interferon alpha2b, INSTILADRIN
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INSTILADRINDrug
Also called rAd-IFN/Syn3
The INSTILADRIN components will be mixed with a diluent. The total dose will be given as a single, one-hour intravesical administration which may, depending on clinical response, be repeated every 3 months up to a maximum of 4 instillations.
| Study group | Role | What they receive |
|---|---|---|
| rAd-IFN Dose 1x10^11vps/ml | Experimental | Subjects will be randomly assigned to one of two INSTILADRIN arms. Receives: Drug: INSTILADRIN |
| rAd-IFN dose 3x10^11 vps/ml | Experimental | Subjects will be randomly assigned to one of two INSTILADRIN arms. Receives: Drug: INSTILADRIN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of High Grade-Recurrence Free Survival at 360 Days
Following the initial treatment, patients were clinically evaluated and re-treated at the Days 90, 180, and 270 time points, as outlined below. The decision to repeat treatment was determined by the clinical response observed following the previous treatment(s). Patients were assessed for High-Grade disease recurrence by cytology, cystoscopy and, if clinically indicated, biopsies were performed to obtain accurate staging. If no evidence of recurrence of High-Grade disease was detected, then a further dose of rAd-IFN/Syn3 was administered as maintenance therapy. Patients who had recurrence of High-Grade disease were withdrawn from treatment but were followed for survival and time to cystectomy. At 360 Days, a final efficacy evaluation was performed for patients receiving 4 doses of drug. This included cystoscopy, cytology, and biopsy.
Measured: 360 Days
Secondary outcomes (12)
Safety of rAd-IFN/Syn3
Treatment Emergent Adverse Events (AEs) for patients receiving study drug were described by NCI-CTCAE V4.03 terminology according to System Organ Class.
Measured: 360 Days
Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days).
All patients were evaluated 3 Months (90 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received another dose. Data are presented as the number and percent of patients with High-Grade disease recurrence.
Measured: 90 Days
Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days).
All patients were evaluated 6 Months (180 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received another dose. Data are presented as the number and percent of patients with High-Grade disease recurrence.
Measured: 180 Days
Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days).
All patients were evaluated 9 Months (270 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received a final dose. Data are presented as the number and percent of patients with High-Grade disease recurrence.
Measured: 270 Days
Incidence of Cystectomy in All Patients
This secondary objective measures the incidence of cystectomy at 360 Days for the Efficacy Analysis Set.
Measured: 360 Days
Overall Survival in All Patients.
Overall survival was defined as the number who survived from the first dose of rAd-IFN/Syn3 to the end of the primary assessment (360 Days) or Withdrawal.
Measured: 360 Days
Number of Patients With Elevated Levels of Viral Vector in Blood
The level of viral vector as measured by qPCR in blood was determined in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103.
Measured: 103 Days
Number of Patients With Elevated Levels of Viral Vector in Urine
The level of viral vector as measured by qPCR in urine was determined in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103.
Measured: 103 Days
Number of Patients With Elevated IFN alpha2b Protein Levels in Serum
The levels of serum IFN alpha2b protein as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent doses at Day 91 (pre-dose), Day 92, Day 94, Day 103, Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal.
Measured: 360 Days
Number of Patients With Elevated IFN alpha2b Protein Levels in Urine
The levels of urine IFN alpha2b protein as measured by ELISA were measured in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that did not have recurrence of HGD and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103.
Measured: 103 Days
Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum
The levels of serum anti-IFN alpha2b antibodies as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent doses at Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal.
Measured: 360 Days
Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum.
The levels of serum anti-adenovirus type 5 antibodies as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent subsequent doses at Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal.
Measured: 360 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2012 (estimated)
- Study startSep 2012
- Primary completionOct 2015
- Study completionJan 2016
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 (2)Papers the sponsor has linked to this study.
- Other trials for Superficial 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- FKD Therapies Oy
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Colin Dinney, MD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01687244
- Sponsor's protocol ID
- rAd-IFN-CS-002
- Status last verified
- Jun 2017
- First submitted
- 6 Sep 2012
- Last updated
- 24 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: A manuscript will be published on the results of the study
Publications
Konety BR, Lotan Y, Myers A. Safety of nadofaragene firadenovec-vncg: review of data from phase 2 and phase 3 studies. Can J Urol. 2025 Mar 18;32(1):29-36. doi: 10.32604/cju.2025.064710.
PubMed 40194933Shore ND, Boorjian SA, Canter DJ, Ogan K, Karsh LI, Downs TM, Gomella LG, Kamat AM, Lotan Y, Svatek RS, Bivalacqua TJ, Grubb RL 3rd, Krupski TL, Lerner SP, Woods ME, Inman BA, Milowsky MI, Boyd A, Treasure FP, Gregory G, Sawutz DG, Yla-Herttuala S, Parker NR, Dinney CPN. Intravesical rAd-IFNalpha/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study. J Clin Oncol. 2017 Oct 20;35(30):3410-3416. doi: 10.1200/JCO.2017.72.3064. Epub 2017 Aug 23.
PubMed 28834453
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Open Label, Parallel Arm Study to Evaluate the Safety and Efficacy of rAd-IFN/Syn3 Following Intravesical Administration in Subjects With High Grade, BCG Refractory or Relapsed Superficial Bladder Cancer
- ClinicalTrials.gov ID
- NCT01687244
- Acronym / sponsor ID
- rAd-IFN-CS-002
- Conditions
- Superficial Bladder Cancer
- Keywords
- BCG Refractory or Relapsed Superficial Bladder Cancer, rAd-IFN, Syn3, Intravesical, transitional cell carcinoma of the bladder, superficial non-muscle invasive tumor, Interferon alpha2b, INSTILADRIN
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- FKD Therapies OyIndustry (pharma, biotech, devices)
- Study start
- Sep 2012
- Primary completion
- Oct 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 18 Sep 2012 (estimated)
- Results
- Posted 30 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 2 study is designed to assess the efficacy and safety of INSTILADRIN (rAd-IFN with Syn3) when given intravesically to patients with high grade non-muscle invasive bladder cancer who are refractory to or have relapsed from BCG therapy. The pharmacodynamics of INSTILADRIN will also be studied by measuring the interferon (IFNα2b) levels excreted in the urine. rAd-IFN is a non-replicating recombinant adenovirus type 5 (Ad5)-vector encoding the interferon alpha-2b (IFNα2b) gene. Syn 3 is clinical surfactant excipient which enhances the ability of the adenoviral vector to transfect cells in the bladder wall.
Detailed description
Criteria for Evaluation:
Efficacy: A Response is defined as no evidence of recurrence of a high grade tumor by cystoscopy, cytology or if clinically indicated, biopsy.
Safety: The safety and tolerability of INSTILADRIN will be evaluated based on adverse event reports, vital signs, ECGs, clinical laboratory values and results of physical examination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rAd-IFN Dose 1x10^11vps/ml | Experimental | Drug: INSTILADRINSubjects will be randomly assigned to one of two INSTILADRIN arms. |
| rAd-IFN dose 3x10^11 vps/ml | Experimental | Drug: INSTILADRINSubjects will be randomly assigned to one of two INSTILADRIN arms. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Aged 18 years or older at the time of consent
- Able to give informed consent
- Subjects with high grade BCG-refractory or relapsed NMIBC including
- Relapse is defined as recurrence within 1 year after a complete response to BCG treatment
- Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment
Key exclusion criteria (13 listed)
- Current or previous evidence of muscle invasive or metastatic disease
- Current systemic therapy for bladder cancer
- Current or prior pelvic external beam radiotherapy
- Prior treatment with adenovirus-based drugs
- Suspected hypersensitivity to interferon alpha
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 |
|---|---|---|
| INSTILADRINAlso: rAd-IFN/Syn3The INSTILADRIN components will be mixed with a diluent. The total dose will be given as a single, one-hour intravesical administration which may, depending on clinical response, be repeated every 3 months up to a maximum of 4 instillations. | Drug | rAd-IFN Dose 1x10^11vps/ml, rAd-IFN dose 3x10^11 vps/ml |
Primary outcome
Incidence of High Grade-Recurrence Free Survival at 360 Days
Time frame: 360 Days
Following the initial treatment, patients were clinically evaluated and re-treated at the Days 90, 180, and 270 time points, as outlined below. The decision to repeat treatment was determined by the clinical response observed following the previous treatment(s). Patients were assessed for High-Grade disease recurrence by cytology, cystoscopy and, if clinically indicated, biopsies were performed to obtain accurate staging. If no evidence of recurrence of High-Grade disease was detected, then a further dose of rAd-IFN/Syn3 was administered as maintenance therapy. Patients who had recurrence of High-Grade disease were withdrawn from treatment but were followed for survival and time to cystectomy. At 360 Days, a final efficacy evaluation was performed for patients receiving 4 doses of drug. This included cystoscopy, cytology, and biopsy.
12 secondary outcomes
Safety of rAd-IFN/Syn3
Time frame: 360 Days
Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days).
Time frame: 90 Days
Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days).
Time frame: 180 Days
Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days).
Time frame: 270 Days
Incidence of Cystectomy in All Patients
Time frame: 360 Days
Overall Survival in All Patients.
Time frame: 360 Days
Number of Patients With Elevated Levels of Viral Vector in Blood
Time frame: 103 Days
Number of Patients With Elevated Levels of Viral Vector in Urine
Time frame: 103 Days
Number of Patients With Elevated IFN alpha2b Protein Levels in Serum
Time frame: 360 Days
Number of Patients With Elevated IFN alpha2b Protein Levels in Urine
Time frame: 103 Days
Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum
Time frame: 360 Days
Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum.
Time frame: 360 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40194933Konety BR, Lotan Y, Myers A. Safety of nadofaragene firadenovec-vncg: review of data from phase 2 and phase 3 studies. Can J Urol. 2025 Mar 18;32(1):29-36. doi: 10.32604/cju.2025.064710.
- Derived from this study: PubMed 28834453Shore ND, Boorjian SA, Canter DJ, Ogan K, Karsh LI, Downs TM, Gomella LG, Kamat AM, Lotan Y, Svatek RS, Bivalacqua TJ, Grubb RL 3rd, Krupski TL, Lerner SP, Woods ME, Inman BA, Milowsky MI, Boyd A, Treasure FP, Gregory G, Sawutz DG, Yla-Herttuala S, Parker NR, Dinney CPN. Intravesical rAd-IFNalpha/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study. J Clin Oncol. 2017 Oct 20;35(30):3410-3416. doi: 10.1200/JCO.2017.72.3064. Epub 2017 Aug 23.
- Individual participant dataSharing planned: No. A manuscript will be published on the results of the study
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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.
Colin Dinney, MD study chair
M.D. Anderson Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing INSTILADRIN in people with Superficial Bladder Cancer, run by FKD Therapies Oy.
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 25 inclusion and 13 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: finished, as of the sponsor's last update on 24 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 30 May 2017). 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?
Incidence of High Grade-Recurrence Free Survival at 360 Days (time frame: 360 Days). 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 NCT01687244, which also lists 2 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 24 Jul 2017.