AzTrials
AzTrials

Superficial Bladder CancerPhase 3NCT02773849

ADSTILADRIN (=INSTILADRIN) in Patients With High-Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

A Phase 3 study testing ADSTILADRIN in people with Superficial Bladder Cancer, run by Ferring Pharmaceuticals at 34 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Previous multi-dose Phase I and Phase II clinical studies have demonstrated that ADSTILADRIN is a safe and effective treatment for BCG-refractory and recurrent NMIBC. This Phase III study is designed to expand those observations using a high dose of ADSTILADRIN in patients that are "BCG Unresponsive" which refers to… 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?
ADSTILADRIN
Could I receive a placebo?
No, everyone receives an active treatment
How many people
157 participants
Where
34 sitesUnited States
Study dates
19 Sep 2016to 24 May 2023
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

  • Aged 18 years or older at the time of consent
  • Able to give informed consent
  • Had, at entry, confirmed by a pathology report:
  • Carcinoma in situ (CIS) only; Ta/T1 high-grade disease with concomitant CIS; or Ta/T1 high-grade disease without concomitant CIS
  • Are "BCG Unresponsive" which refers to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response (CR) to BCG, relapsed with high-grade CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria defined the patients who were eligible for inclusion in the study:
  • Had received at least 2 previous courses of BCG within a 12 month period. This was defined as at least 5 of 6 induction BCG instillations and at least 2 out of 3 instillations of maintenance BCG, or at least 2 of 6 instillations of a second induction course, where maintenance BCG was not given;
Show all 18Show fewer
  • Exception: those who had T1 high-grade disease at first evaluation after induction BCG alone (at least 5 of 6 doses) qualified in the absence of disease progression.
  • At the time of tumor recurrence, patients with CIS alone or high-grade Ta/T1 with CIS were within 12 months of last exposure to BCG and patients with high-grade Ta/T1 without CIS were within 6 months of last exposure to BCG;
  • No maximum limit to the amount of BCG administered; and
  • All visible papillary tumors were required to be resected and those with persistent T1 disease on transurethral resection of bladder tumor (TURBT) underwent an additional re-TURBT within 14 to 60 days prior to beginning study treatment. Obvious areas of CIS should also be fulgurated.
  • Available for the whole duration of the study
  • Life expectancy >2 years, in the opinion of the investigator
  • Eastern Cooperative Oncology Group (ECOG) status 2 or less
  • Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or magnetic resonance imaging (MRI) with or without urogram performed within 6 months of enrollment
  • Patients with prostate cancer on active surveillance at low risk for progression, defined as Prostate-Specific Antigen (PSA) < 10 ng/dL, Gleason score 6 and clinical stage tumor-1 (cT1) were permitted to be in the study at the discretion of the investigator (see exclusion criterion 10).
  • Female patients of childbearing potential were required to use maximally effective birth control during the period of therapy, were required to use contraception for 1 month following the last study drug infusion and were required to have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female patients were required to be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. 'Maximally effective birth control' meant that the patient, if sexually active, used a combination of two methods of birth control that were approved and recognized to be effective by Regulatory Agencies
  • Male patients were required to 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; and
  • Adequate lab values

Who cannot join

  • Current or previous evidence of muscle invasive (muscularis propria) or metastatic disease presented at the screening visit. Examples of increased risk of metastatic disease included (but were not limited to):
  • Presence of lymphovascular invasion and/micropapillary disease as shown in the histology of the biopsy sample; and
  • Patients with T1 disease accompanied by the presence of hydronephrosis secondary to the primary tumor
  • Current systemic therapy for bladder cancer
  • Current or prior pelvic external beam radiotherapy within 5 years of entry
  • Prior treatment with adenovirus-based drugs
Show all 17Show fewer
  • Suspected hypersensitivity to IFN alfa2b
  • Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily treated, patients could have entered the study)
  • Clinically significant and unexplained elevated liver or renal function tests
  • Women who were pregnant or lactating or refused to commit to use contraception throughout the study
  • Any other significant disease or other clinical findings which, in the opinion of the investigator, prevented study entry
  • History of malignancy of another organ system within the past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ≤ pathological tumor-2 (pT2) upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also patients with genitourinary cancers other than urothelial cancer or prostate cancer that were under active surveillance were excluded (see inclusion criterion 9)
  • Patients who could not hold instillation for 1 hour
  • Patients who could not tolerate intravesical dosing or intravesical surgical manipulation; and
  • Intravesical therapy within 8 weeks prior to beginning study treatment with the exception of:
  • cytotoxic agents (e.g. Mitomycin C, doxorubicin and epirubicin) when administered as a single instillation immediately following a TURBT procedure which was permitted between 14 to 60 days prior to beginning study treatment
  • previous intravesical BCG therapy, which could be given at least 5 weeks before the diagnostic biopsy required for entry into the study

Trial locations and contacts

34 sites in 1 country.

34 sites in 1 country

United States34 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University School of Medicine

    Atlanta, Georgia, 30322

  • Johns Hopkins Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • University of North Carolina (UNC) - Chapel Hill

    Chapel Hill, North Carolina, 27599-7235

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • University of Chicago - Comprehensive Cancer Research Center

    Chicago, Illinois, 60637

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • The Urology Center of Colorado

    Denver, Colorado, 80211

  • Duke University

    Durham, North Carolina, 27710

  • University of Florida - UF Health Davis Center Pavilion and Shands Med Plaza

    Gainesville, Florida, 32610

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Spectrum Health Medical Group

    Grand Rapids, Michigan, 49546

  • Regional Urology

    Greenville, South Carolina, 29605

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Baylor College of Medicine

    Houston, Texas, 77030

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Keck School of Medicine at USC Medical Center

    Los Angeles, California, 90089

  • University of Wisconsin - Madison

    Madison, Wisconsin, 53705

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • West Virginia University Cancer Institute

    Morgantown, West Virginia, 26506

  • Carolina Urologic research Center

    Myrtle Beach, South Carolina, 29572

  • Vanderbilt University Medical Center Dept. of Urologic Surgery

    Nashville, Tennessee, 37232

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • The University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • The Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55905

  • The Univ. of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229-3900

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • SUNY Upstate Medical Center

    Syracuse, New York, 13210

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • Urology of Virginia

    Virginia Beach, Virginia, 23462

  • Delaware Valley Urology, LLC

    Voorhees Township, New Jersey, 08043

Other trials in United States

About this study

Official title: A Phase III, Open Label Study to Evaluate the Safety and Efficacy of INSTILADRIN® (rAd-IFN)/Syn3) Administered Intravesically to Patients With High-Grade, BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

Previous multi-dose Phase I and Phase II clinical studies have demonstrated that ADSTILADRIN is a safe and effective treatment for BCG-refractory and recurrent NMIBC. This Phase III study is designed to expand those observations using a high dose of ADSTILADRIN in patients that are "BCG Unresponsive" which refers to patients with high-grade NMIBC who are unlikely to benefit from and should not receive further intravesical BCG.

Read the detailed description

Recombinant IFN alpha2b has pleiotropic effects that contribute to antitumor activity in Non-Muscle Invasive Bladder Cancer (NMIBC). ADSTILADRIN is a non-replicating adenovirus vector harboring the human IFN alpha2b gene. When combined with the excipient Syn3, intravesical administration of the rAd-IFN results in transduction of the virus into the epithelial cell lining in the bladder. The IFN alpha2b gene is incorporated into the cellular DNA resulting in the synthesis and expression of large amounts of IFN alpha2b protein. Clinical studies have confirmed that IFN alpha2b protein can be measured in the urine of patients treated with ADSTILADRIN within 24 hours after dosing.

Being tested
ADSTILADRIN
Keywords
IFN, BCG-unresponsive, Non-Muscle Invasive Bladder Cancer (NMIBC)
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.

  • ADSTILADRINBiological

    Also called rAd-IFN/SYN3NODA, INSTILADRIN

Study groups in NCT02773849
Study groupRoleWhat they receive
ADSTILADRINExperimentalIntravesical administration of ADSTILADRIN into the bladder
Receives: Biological: ADSTILADRIN

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With a Complete Response Rate Based on Patients With Carcinoma in Situ (CIS), With or Without Concomitant High-grade Ta or T1 Papillary Disease.

    A patient in the CIS cohort was judged to have achieved CR where urine cytology was reported as normal, atypical, degenerative, reactive, inflammatory, or nonspecific AND cystoscopy was reported as normal or with findings that did not include evidence of low-grade or high-grade recurrence. Bladder biopsy, if performed (not mandatory), demonstrated an absence of low-grade or high-grade recurrence.

    Measured: 12 Months

Secondary outcomes (8)

  1. Durability of Complete Response in Patients With CIS (With or Without Concomitant Ta or T1 Papillary Disease) Who Achieve a Complete Response.

    Durability of complete response (CR) was defined as the time from first observed CR to the documented treatment failure. Patients without treatment failure were censored at the last disease assessment not showing treatment failure, where treatment failure was defined as high-grade disease recurrence, disease progression, or death, whichever occurred earlier.

    Measured: Up to 57 months

  2. Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS)

    Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder. Incidence of HGRF survival at Months 3, 6, 9, and 12, and every 3 months up to Month 24, and then at Months 36, 48, and 57.

    Measured: up to 57 months

  3. Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS)

    HGRF survival was defined as the time from the first dose to the first recurrence of high-grade disease (including muscle-invasive disease progression and death due to any cause). Patients without high-grade disease recurrence were censored at the last disease assessment not showing high-grade disease recurrence.

    Measured: Up to 57 months

  4. Incidence of Cystectomy at 12 Months, 2 Years and 5 Years

    The incidence of cystectomy is described as the proportion of patients undergoing radical cystectomy for any reason after the first dose, within 12 months, 2 years and 5 years.

    Measured: 60 Months

  5. Overall Survival Rate in All Patients

    Overall survival rate was defined as the time from the first dose to death due to any cause. Patients who were still alive were censored at the last date the patient was known to be alive. Overall survival rate is a Kaplan-Meier estimate of the survivor function at each specific time point. The 95% CI is calculated using the Greenwood's formula with a log-log transformation. Percentage is calculated using the number of patients in the column heading as the denominator.

    Measured: 60 Months

  6. Anti-adenoviral Antibody Levels for Correlation to Response Rate

    Measurement of anti-adenoviral antibody levels at each dosing period, withdrawal, and at 12 months were done. A patient was considered to have a positive immunogenic response in anti-adenoviral antibodies if a post-baseline titration demonstrated a greater than a 2-fold dilution increase from baseline.

    The table represent data at any time during the 12 months period, which means that the patients were included in the Yes group if they at any measurement during the trial had a 2-fold dilution increase from baseline.

    Measured: 12 Months

  7. Safety of ADSTILADRIN

    The type, incidence, relatedness and severity of treatment emergent adverse events of ADSTILADRIN as assessed by NCI-CTCAE V4.03 were monitored.

    Measured: 60 Months

  8. Durability of Response During the Long-term Follow-up Period.

    Durability will be measured by determining the number of patients without recurrence of high-grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder if clinically indicated.

    Measured: Up to 60 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2016 (estimated)
  2. Study start19 Sep 2016
  3. Primary completion24 May 2019
  4. Study completion24 May 2023

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
157 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02773849
Sponsor's protocol ID
rAd-IFN-CS-003
Other IDs
000418
Status last verified
Jul 2024
First submitted
19 Apr 2016
Last updated
29 Jul 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
Individual data sharing
No

Publications

  • Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM, Bivalacqua TJ, Montgomery JS, Lerner SP, Busby JE, Poch M, Crispen PL, Steinberg GD, Schuckman AK, Downs TM, Svatek RS, Mashni J Jr, Lane BR, Guzzo TJ, Bratslavsky G, Karsh LI, Woods ME, Brown G, Canter D, Luchey A, Lotan Y, Krupski T, Inman BA, Williams MB, Cookson MS, Keegan KA, Andriole GL Jr, Sankin AI, Boyd A, O'Donnell MA, Sawutz D, Philipson R, Coll R, Narayan VM, Treasure FP, Yla-Herttuala S, Parker NR, Dinney CPN. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021 Jan;22(1):107-117. doi: 10.1016/S1470-2045(20)30540-4. Epub 2020 Nov 27.

    PubMed 33253641

  • 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 40194933

  • Narayan VM, Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM, Bivalacqua TJ, Montgomery JS, Lerner SP, Busby JE, Poch M, Crispen PL, Steinberg GD, Schuckman AK, Downs TM, Mashni J Jr, Lane BR, Guzzo TJ, Bratslavsky G, Karsh LI, Woods ME, Brown G, Canter D, Luchey A, Lotan Y, Inman BA, Williams MB, Cookson MS, Chang SS, Sankin AI, O'Donnell MA, Sawutz D, Philipson R, Parker NR, Yla-Herttuala S, Rehm D, Jakobsen JS, Juul K, Dinney CPN. Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guerin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial. J Urol. 2024 Jul;212(1):74-86. doi: 10.1097/JU.0000000000004020. Epub 2024 May 5.

    PubMed 38704840

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ADSTILADRIN in people with Superficial Bladder Cancer, run by Ferring Pharmaceuticals at 34 sites in United States.

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 18 inclusion and 17 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 29 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States. 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. 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 Jul 2022). 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?

Number of Patients With a Complete Response Rate Based on Patients With Carcinoma in Situ (CIS), With or Without Concomitant High-grade Ta or T1 Papillary Disease. (time frame: 12 Months). 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 NCT02773849, 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 29 Jul 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in