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Evaluating a new treatment for high-grade bladder cancer

A Phase 3, Randomised, Multi-center, Open Label Trial to Evaluate the Safety and Efficacy of Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade Bacillus Calmette-Guerin Therapy (BCG) Unresponsive Non-muscle Invasive Bladder Cancer (NMIBC)

Phase 3 Interventional Ferring Pharmaceuticals · NCT06545955

This study is testing a new treatment for people with high-grade bladder cancer that hasn't responded to previous therapy to see if it can help them get better.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment250 (estimated)
Ages18 Years and up
SexAll
SponsorFerring Pharmaceuticals Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy
Locations73 sites (Tucson, Arizona and 72 other locations)
Trial IDNCT06545955 on ClinicalTrials.gov

What this trial studies

This trial evaluates the safety and efficacy of intravesical nadofaragene firadenovec, both alone and in combination with chemotherapy or immunotherapy, for patients with high-grade non-muscle invasive bladder cancer that is unresponsive to prior Bacillus Calmette-Guerin (BCG) therapy. Participants must have documented carcinoma in situ (CIS) and have received at least two courses of BCG treatment within the last year. The study aims to determine the effectiveness of this new treatment approach in achieving a complete response in affected patients.

Who should consider this trial

Good fit: Ideal candidates are patients diagnosed with carcinoma in situ (CIS) ± high-grade Ta/T1 disease who are BCG-unresponsive.

Not a fit: Patients who have not received at least two courses of BCG therapy or those with muscle-invasive bladder cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with high-grade bladder cancer who have not responded to standard BCG therapy.

How similar studies have performed: Previous studies have shown promising results with nadofaragene firadenovec, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Diagnosed, as documented, with carcinoma in situ (CIS) ±Ta/T1 high-grade disease.

  * For T1 disease biopsies should contain muscle fibres.
* Unresponsive to ≥2 courses of Bacillus Calmette-Guerin (BCG) therapy within the last 12 months. BCG-unresponsive refers to participants with high-grade non-muscle invasive bladder cancer (NMIBC) who are unlikely to benefit from and who will not be receiving further intravesical BCG. The term "BCG-Unresponsive" includes participants who did not respond to BCG treatment and have a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response to BCG, relapse with CIS within 12 months of their last intravesical treatment with BCG or relapse with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria define the participants who may be included in the trial:

  * Have received at least 2 courses of BCG within a 12 month period - defined as at least 5 of 6 induction BCG instillations and at least 2 of 3 instillations of maintenance BCG, or at least 2 of 6 instillations of a second induction course, where maintenance BCG is not given.

    o Exception: those who have T1 high-grade disease at 1st evaluation after induction BCG alone (at least 5 of 6 doses) may qualify in the absence of disease progression
  * At the time of tumour recurrence, participants with CIS alone or high-grade Ta/T1 with CIS should be within 12 months of last exposure to BCG
  * No maximum limit to the amount of BCG administered
  * All visible papillary tumours must be resected and those with persistent T1 disease on transurethral resection of bladder tumour (TURBT) should undergo an additional re-TURBT within 14 to 70 days prior to beginning trial treatment. Obvious areas of CIS should also be fulgurated
* Eastern Cooperative Oncology Group (ECOG) status ≤2
* Aged ≥18 years at the time of consent
* Available for the whole duration of the trial
* Life expectancy \>2 years, in the opinion of the investigator
* 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 tumour 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 enrolment. Absence of locally advanced disease as assessed by CT scan or MRI
* Participants who elect not to undergo cystectomy
* Participants with prostate cancer on active surveillance at low risk for progression are permitted to be included into the trial at the discretion of the investigator
* 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 and for 6 months following the last dose. Otherwise, female participants must be post-menopausal (no menstrual period for a minimum of 12 months, as confirmed by follicle-stimulating hormone levels) or surgically sterile
* Male subjects must be willing to use a male condom and effective contraception during sex throughout the treatment period and for 3 months following the last dose.

Exclusion Criteria:

* Current or previous evidence of muscle-invasive (muscularis propria) or metastatic disease presented at the screening visit. Examples of increased risk of muscle-invasive disease include but are not limited to:

  * Presence of lymphovascular invasion and / or micropapillary, sarcomatoid, plasmacytoid and / or neuroendocrine disease as shown in the histology of the biopsy sample
  * Participants with CIS+T1 disease accompanied by the presence of hydronephrosis secondary to the primary tumour
* Current systemic therapy for bladder cancer other than investigational medicinal products used in randomisation arm
* Current or prior investigational treatment for BCG-unresponsive NMIBC or any other investigational drug (drug used in a clinical trial, i.e drug used in a Ferring sponsored non interventional study does not apply) within 1 month prior to screening
* Current or prior pelvic external beam radiotherapy within 2 years of screening
* Prior treatment with nadofaragene firadenovec at any time
* Prior systemic therapy for bladder cancer at any time
* Prior intravesical chemotherapy for the treatment of BCG-unresponsive NMIBC

Where this trial is running

Tucson, Arizona and 72 other locations

+23 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-muscle Invasive Bladder Cancer With Carcinoma in Situ
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.