Low-grade UTUC Treated With Nadofaragene Firadenovec Administered to Renal Pelvis

NCT06668493 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 000425U1111-1292-0846
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

Brief Summary

The primary purpose of this trial is to evaluate the safety \& tolerability of Nadofaragene Firadenovec in subjects with LG-UTUC. To help with this evaluation, a safety lead-in period will be conducted for the first 6 subjects. Complete response is at 3 or 6 months defined as absence of any UTUC in the renal pelvis.

Conditions

Low-grade Upper Tract Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• The number of treatment-emergent adverse events reported by each subject during the trial.

  Up to 30 months

• Complete response

  defined as absence of any UTUC in the renal pelvis, i.e. negative urine cytology for high-grade urothelial carcinoma (centrally assessed), and either no suspicious lesions on ureteroscopy (investigator assessed) or a negative for-cause biopsy (centrally assessed).

  Up to 6 months

Secondary Outcomes (8)

• Occurrence of anti-adenoviral antibodies.

  Up to 30 months

• Occurrence of anti-interferon-α2b (IFN-α2b) antibodies.

  Up to 30 months

• Shedding of adenoviral vector with IFN-α2b.

  Before dose and up to 15 days after dose

• Systemic exposures to IFN-α2b protein.

  Before dose and up to 15 days after dose

• Systemic exposures to adenoviral vector with IFN-α2b.

  Before dose and up to 15 days after dose

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Nadofaragene Firadenovec

Interventions

Nadofaragene Firadenovec DRUG

Repeat dose trial to investigate the safety and efficacy of nadofaragene firadenovec instilled into the renal pelvis

Also known as: Adstiladrin

Treatment

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 at the time of signing informed consent.
• Able to give written informed consent.
• Have biopsy-proven low-grade upper tract urothelial cancer (LG-UTUC) confirmed by a pathology report ≤2 months prior to enrolment.
• Have ≥1 measurable papillary low-grade tumour (5-15 mm in maximum diameter), evaluated visually above the ureteropelvic junction before enrolment.
• Subjects with low-grade tumour larger than 15 mm will be eligible if endoscopic downsizing of the tumour to 5-15 mm in maximum diameter has been performed before enrolment.
• Willing to be available for at least 18 months after first dosing.
• Have life expectancy \>2 years, in the opinion of the investigator.
• Have an Eastern Cooperative Oncology Group (ECOG) status of 2 or less.
• Females of reproductive potential must have a negative highly sensitive urine or serum pregnancy test upon entry into this trial and be willing to use highly effective contraception during treatment with the investigational medicinal product (IMP) and for 6 months following the last dose. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. Highly effective methods of contraception include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, and sexual abstinence.
• Male subjects with female partners of reproductive potential must be surgically sterile or willing to use a condom in addition to effective contraception in their female partner during treatment with the IMP and for 3 months following the last dose.
• Adequate laboratory values:
• haemoglobin ≥10 g/dL
• white blood cells (WBC) ≥4000/μL
• absolute neutrophil count (ANC) ≥2000/μL
• platelet count ≥100,000/μL

You may not qualify if:

• UTUC characterised by one or more of the following:
• High-grade cytology or high-grade histology
• Multi-focal UTUC
• Exception: Subjects with low-grade multi-focal tumours will be eligible if any ureteral tumours can be ablated before enrolment and if the total diameter of the multifocal tumours above the ureteropelvic junction is not exceeding 15 mm in diameter.
• Bilateral disease
• Exception: Subjects who have had bilateral disease are eligible (not in the safety lead-in) if one renal unit is removed or rendered disease-free by endoscopic ablation before enrolment.
• Current or previous evidence of carcinoma in situ, of muscle invasive (muscularis propria) urothelial cancer in the urogenital tract presented at the screening visit.
• Concomitant lower tract urothelial carcinoma and/or concomitant or prior urothelial carcinoma within the prostatic urethra.
• History of high grade papillary urothelial cancer within 2 years prior to screening.
• Current or prior treatment with mitomycin gel and/or any investigational drug for the treatment of UTUC.
• Current systemic chemo- or immunotherapy for bladder cancer or any other malignancy.
• Current or prior investigational treatment for Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) or any other investigational drug within 1 month prior to screening.
• Current or prior retroperitoneal external beam radiotherapy within 5 years of screening.
• Prior treatment with adenovirus-based drugs including use of other adenovirus vector medications, including COVID-19 vaccines, within 2 weeks before instillation.
• Suspected and/or a medical history of hypersensitivity to nadofaragene firadenovec, interferon-α2b (IFN-α2b) and/or adenovector medications.

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (7)

Mayo Clinic - Scottsdale Arizona

Scottsdale, Arizona, 85054, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

Mayo Clinic - Rochester Minnesota

Rochester, Minnesota, 55905, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

University of Pennsylvania - Perelman Center for Advanced Medicine - Penn Urology

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MD Anderson Cancer Center - Genitourinary (GU) Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Study Officials

• Global Clinical Compliance

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Ferring Pharmaceuticals

CONTACT

1-888-337-7464; Disclosure@ferring.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: October 31, 2024
• Study Start: June 12, 2025
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2029
• Last Updated: February 27, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)