A phase 2, randomised, multi-centre, open label trial to evaluate the safety and efficacy ofintravesical nadofaragene firadenovec alone or in combination with chemotherapy(gemcitabine and docetaxel) or immunotherapy (pembrolizumab) in subjects with high-grade Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) (ABLE-22)
Studying the Safety and Effectiveness of Bladder-Administered Therapy for BCG-Unresponsive Bladder Cancer
Hristos Kaimakliotis, MD
Primary Investigator
Brief description of study
The pivotal phase 2 trial (rAd-IFN-CS 003) evaluating the efficacy of nadofaragene firadenovec showed that 55 (53.4%) of 103 subjects with CIS ± high-grade Ta/T1 achieved a complete response (CR) at 3 months. In this trial, the safety and efficacy of intravesical instillation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy will be evaluated in participants with NMIBC CIS (± high-grade Ta/T1).
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Non-muscle Invasive Bladder Cancer With Carcinoma in Situ
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Age: 18 years - 100 years
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Gender: All
Inclusion Criteria:
- Diagnosed, as documented, with carcinoma in situ (CIS) ±Ta/T1 high-grade disease.
- Unresponsive to ≥2 courses of Bacillus Calmette-Guerin (BCG) therapy within the last 12 months. BCG-unresponsive refers to subjects 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 subjects 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 subjects 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, subjects 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
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
- Subjects 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
This study investigates the safety and efficacy of intravesical nadofaragene firadenovec, either alone or in combination with chemotherapy or immunotherapy, in patients with high-grade Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC). NMIBC is a type of bladder cancer that has not spread into the muscle layer of the bladder. The study aims to evaluate the response of the cancer to the treatment, particularly for those who did not respond well to BCG therapy.
Participants will receive intravesical instillations, which means the treatment is administered directly into the bladder. The study will compare the effects of nadofaragene firadenovec alone, or combined with chemotherapy agents like gemcitabine and docetaxel, or with the immunotherapy agent pembrolizumab. The study will monitor the participants for any side effects and measure their response to the treatment over time.
- Who can participate: Participants must have carcinoma in situ (CIS) with or without high-grade Ta/T1 disease and be unresponsive to at least two BCG courses in the last 12 months. All visible tumors must be resected, and any persistent T1 disease should undergo additional resection before starting the trial treatment.
- Study details: Participants will receive treatments directly into the bladder, possibly including nadofaragene firadenovec alone or with other therapies. The study will monitor side effects and assess the treatment's effectiveness in managing bladder cancer.
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