NCT06545955招募中3 期
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)
Ferring Pharmaceuticals112 个研究点 分布在 5 个国家目标入组 250 人开始时间: 2024年10月1日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 250
- 试验地点
- 112
- 主要终点
- Complete response
研究概览
简要总结
The pivotal phase 3 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Nadofaragene firadenovec
Experimental
Nadofaragene firadenovec (intravesical)
干预措施: Nadofaragene Firadenovec (Drug)
Nadofaragene firadenovec + gemcitabine & docetaxel
Experimental
Nadofaragene firadenovec (intravesical), and sequential gemcitabine and docetaxel (intravesical)
干预措施: Docetaxel (Drug)
Nadofaragene firadenovec + gemcitabine & docetaxel
Experimental
Nadofaragene firadenovec (intravesical), and sequential gemcitabine and docetaxel (intravesical)
干预措施: Gemcitabine (Drug)
Nadofaragene firadenovec + gemcitabine & docetaxel
Experimental
Nadofaragene firadenovec (intravesical), and sequential gemcitabine and docetaxel (intravesical)
干预措施: Nadofaragene Firadenovec (Drug)
Nadofaragene firadenovec + Pembrolizumab
Experimental
Nadofaragene firadenovec (intravesical), and pembrolizumab (IV infusion).
This arm will be closed and patients will no longer be randomised to this arm. This modification will convert ABLE-22 into a two-arm study with 1:1 randomisation between nadofaragene alone and nadofaragene + gemcitabine/docetaxel, to now N=100 in each of the 2 remaining arms.
Participants already enrolled in this arm will not be impacted.
干预措施: Nadofaragene Firadenovec (Drug)
Nadofaragene firadenovec + Pembrolizumab
Experimental
Nadofaragene firadenovec (intravesical), and pembrolizumab (IV infusion).
This arm will be closed and patients will no longer be randomised to this arm. This modification will convert ABLE-22 into a two-arm study with 1:1 randomisation between nadofaragene alone and nadofaragene + gemcitabine/docetaxel, to now N=100 in each of the 2 remaining arms.
Participants already enrolled in this arm will not be impacted.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Complete response
时间窗: up to 6 months
Complete response (CR) at any time from first treatment (defined as absence of high-grade (HG) recurrence).
次要结局
- Complete response at month 3(3 months)
- Complete response at month 6(6 months)
- Durability of complete response(Up to 24 months)
- Muscle-invasive progression of disease(up to 36 months)
- Cystectomy-free survival(up to 36 months)
- Pathological staging(up to 36 months)
- Overall survival(up to 36 months)
- Evidence of malignant lesions of the upper tract and/or prostatic urethra(up to 24 months)
- Adverse events(up to 36 months)
研究者
研究点 (112)
Loading locations...
相似试验
招募中
3 期
Trial of Nadofaragene Firadenovec vs. Observation in Participants With Intermediate Risk Non-Muscle Invasive Bladder CancerIntermediate Risk Non-Muscle Invasive Bladder CancerNCT06510374Ferring Pharmaceuticals454
招募中
1 期
Low-grade UTUC Treated With Nadofaragene Firadenovec Administered to Renal PelvisNCT06668493Ferring Pharmaceuticals20
已完成
3 期
Multicenter Study of the Safety and Efficacy of NAFT-500 in Tinea PedisAthlete's FootTinea PedisNCT00750139Merz North America, Inc.707
已完成
3 期
Multicenter Study of the Safety and Efficacy of NAFT-500 in Tinea CrurisJock ItchTinea CrurisNCT00750152Merz North America, Inc.334
已完成
3 期
Study of Difluprednate in the Treatment of Inflammation Following Ocular Surgery (ST-601A-002b)InflammationNCT00430092Sirion Therapeutics, Inc.219
相关资讯
Real-World Data and Ongoing Trials Highlight Efficacy of Nadofaragene Firadenovec in Bladder Cancer- Real-world data presented at the 2025 ASCO Genitourinary Cancers Symposium indicates nadofaragene firadenovec demonstrates positive efficacy and safety outcomes in treating NMIBC.
- The ABLE-32 phase 3B trial is underway to assess nadofaragene firadenovec in intermediate-risk NMIBC patients, addressing the unmet need for FDA-approved treatments.
- Additional trials, including ABLE-22 and LUNAR, are exploring nadofaragene firadenovec as a monotherapy, in combination with other treatments, and in low-grade upper tract urothelial carcinoma.
- Nadofaragene firadenovec, the first FDA-approved intravesical gene therapy, offers a novel approach by turning bladder wall cells into interferon microfactories to fight cancer.last yearFerring Advances Nadofaragene Firadenovec Clinical Program in Urothelial Cancers- Ferring Pharmaceuticals is expanding the clinical trial program for nadofaragene firadenovec, an intravesical gene therapy, to include intermediate-risk NMIBC and low-grade UTUC.
- A Phase 2 trial (ABLE-22) will evaluate nadofaragene firadenovec alone or with chemotherapy/immunotherapy in high-risk BCG-unresponsive NMIBC, including re-induction for non-responders.
- The Phase 3B ABLE-32 trial will assess nadofaragene firadenovec in intermediate-risk NMIBC, an area with no FDA-approved treatments, using recurrence-free survival as the primary endpoint.
- The LUNAR trial is initiated to study nadofaragene firadenovec in patients with low-grade upper tract urothelial cancer (UTUC), addressing a significant unmet need.last year