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

NCT02773849 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: rAd-IFN-CS-003000418
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 34

Brief 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 patients with high-grade NMIBC who are unlikely to benefit from and should not receive further intravesical BCG.

Conditions

Superficial Bladder Cancer

Keywords

IFN; BCG-unresponsive; Non-Muscle Invasive Bladder Cancer (NMIBC)

Outcome Measures

Primary Outcomes (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.

  12 Months

Secondary Outcomes (8)

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

  Up to 57 months

• 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)

  up to 57 months

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

  Up to 57 months

• Incidence of Cystectomy at 12 Months, 2 Years and 5 Years

  60 Months

• Overall Survival Rate in All Patients

  60 Months

Study Arms (1)

ADSTILADRIN

EXPERIMENTAL

Intravesical administration of ADSTILADRIN into the bladder

Biological: ADSTILADRIN

Interventions

ADSTILADRIN BIOLOGICAL

Also known as: rAd-IFN/SYN3NODA, INSTILADRIN

ADSTILADRIN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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;
• 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
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead
• FKD Therapies Oy: collaborator
• Society of Urologic Oncology Clinical Trials Consortium: collaborator

Study Sites (34)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Keck School of Medicine at USC Medical Center

Los Angeles, California, 90089, United States

Location

The Urology Center of Colorado

Denver, Colorado, 80211, United States

Location

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

Gainesville, Florida, 32610, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Chicago - Comprehensive Cancer Research Center

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Spectrum Health Medical Group

Grand Rapids, Michigan, 49546, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Delaware Valley Urology, LLC

Voorhees Township, New Jersey, 08043, United States

Location

SUNY Upstate Medical Center

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina (UNC) - Chapel Hill

Chapel Hill, North Carolina, 27599-7235, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

The University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Regional Urology

Greenville, South Carolina, 29605, United States

Location

Carolina Urologic research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Vanderbilt University Medical Center Dept. of Urologic Surgery

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Univ. of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Urology of Virginia

Virginia Beach, Virginia, 23462, United States

Location

West Virginia University Cancer Institute

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53705, United States

Location

Related Publications (2)

• 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.

  PMID: 33253641 RESULT

• 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.

  PMID: 40194933 DERIVED

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Global Clinical Compliance
• Organization: Ferring Pharmaceuticals

Disclosure@ferring.com

+1 862-286-5200

Study Officials

• Stephen Boorjian, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2016
• First Posted: May 16, 2016
• Study Start: September 19, 2016
• Primary Completion: May 24, 2019
• Study Completion: May 24, 2023
• Last Updated: July 29, 2024
• Results First Posted: July 13, 2022

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (34)