BCG + MMC: Adding Mitomycin C to BCG as Adjuvant Intravesical Therapy for High-risk, Non-muscle-invasive Bladder Cancer: a Randomised Phase 3 Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Disease free survival
研究概览
简要总结
Instillation of Bacillus of Calmette-Guerin (BCG) into the urinary bladder (intravesical administration) improves rates of disease recurrence and progression after transurethral resection (TUR) of high risk, non-muscle-invasive bladder cancer (NMIBC), but over 30% of people still develop recurrent transitional cell carcinoma (TCC) despite optimal therapy with adjuvant intravesical BCG. Our meta-analysis, including a recent randomised phase 2 trial, suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both Mitomycin (MM) and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase 3 trial using standard techniques for intravesical administration.
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
- •Males or females with confirmed high grade pTa or stage pT1 (any grade) non-muscle invasive bladder cancer on initial or re-resection histology (concurrent carcinoma in situ is allowed).
- •Age ≥ 18 yrs
- •No macroscopically visible disease at cystoscopy within 8 weeks prior to randomisation. This may either be the initial TURBT at which the primary tumour was completely resected, or a planned second cystoscopy and/ or re-resection done within 8 weeks of the initial TURBT.
- •ECOG Performance Status of 0-2
- •Adequate bone marrow, renal and liver function confirmed by pre-randomisation blood tests.
- •Study treatment both planned and able to start within 4 weeks of randomisation
- •Is willing to complete HRQL questionnaires or is unable to complete them because of literacy, insufficient English or limited vision
- •Willing and able to comply with all study requirements, including treatment, timing and/or nature of all required assessments
- •Signed, written informed consent
排除标准
- •Contraindications or hypersensitivity to investigational products, BCG and MM
- •Prior treatment with any other intravesical agent including BCG or MM (excludes single doses given post TURBT)
- •Current or past transitional cell carcinoma (TCC) of the upper urinary tract
- •Prior muscle-invasive (stage T2 or higher) transitional-cell carcinoma of the bladder
- •Bladder dysfunction precluding intravesical therapy e.g. Severe urinary incontinence or overactive or spastic bladder
- •Life expectancy < 3 months
- •Congenital or acquired immune deficiencies, whether due to a concurrent disease (e.g. acquired immune deficiency syndrome (AIDS), leukaemia, lymphoma) or immunosuppressive therapy (e.g. corticosteroids), or cancer therapy (cytotoxic drugs, radiation)
- •Prior radiotherapy of the pelvis
- •Prior or current treatment with radiotherapy-response or biological-response modifiers
- •Clinical evidence of existing active tuberculosis
- •History of another malignancy within 5 years prior to registration. Patients with non-melanomatous carcinoma of the skin are eligible for this study.
- •Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
- •Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.
研究组 & 干预措施
Arm A: Standard Intravesical BCG
Standard intravesical BCG therapy given as per usual standard of care
干预措施: Bacillus Calmette-Guerin Vaccine Intravesical (Biological)
Arm B: Experimental BCG + MM
Combination therapy with BCG and MM, given on specific protocol sessions
干预措施: Bacillus Calmette-Guerin Vaccine Intravesical (Biological)
Arm B: Experimental BCG + MM
Combination therapy with BCG and MM, given on specific protocol sessions
干预措施: Mitomycin (Drug)
结局指标
主要结局
Disease free survival
时间窗: 5 years follow up
Death, disease free survival, or evidence of transitional cell carcinoma (TCC)
次要结局
- Time to Recurrence(5 years follow up)
- Activity(3 months)
- Time to Progression(5 years follow up)
- Safety and adverse events(During treatment phase of the trial (typically 12 months))
- Health-Related Quality of Life(5 years follow up)
- Overall Survival Time(5 years follow up)
- Feasibility as a future standard of care(During treatment phase of the trial, typically 1 year)
- Marginal Resource Use(5 years follow up)