Adding Mitomycin to Bacillus of Calmette-Guerin (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
- 501
- 试验地点
- 17
- 主要终点
- Disease free survival (death or recurrence)
研究概览
简要总结
Open label, randomised phase 3 trial of the addition of Mitomycin to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer. The study aim is to compare disease-free survival between treatment arms: BCG alone versus Mitomycin in addition to BCG.
详细描述
PROTOCOL SYNOPSIS
Background:
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.
General Aim:
To determine the efficacy and safety of MM in addition to BCG in patients with NMIBC.
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 be either the initial Transurethral Resection of the Bladder Tumour (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
- •Has completed the 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 Mitomycin
- •Prior treatment with any other intravesical agent including BCG or Mitomycin (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 eg. 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
Treatment (Arm B):Intravesical BCG + MM
Induction (weekly x 9); and followed by Maintenance (monthly x 9) beginning 3 months after randomisation.
Dosage of Bacillus of Calmette-Guerin (BCG) dependent on preferred brand of BCG by participating institution. Either 2-8 x 10^8 CFU for OncoTICE or, 81mg for ImmuCYST and TheraCys. Prior to treatment commencement, investigators should nominate which BCG brand will be used. The same brand of BCG must be used for all treatment administered to an individual participant throughout the study.
Dosage of Mitomycin (MM) fixed at 40mg per instillation.
干预措施: Bacillus of Calmette-Guerin (BCG) (Biological)
Treatment (Arm B):Intravesical BCG + MM
Induction (weekly x 9); and followed by Maintenance (monthly x 9) beginning 3 months after randomisation.
Dosage of Bacillus of Calmette-Guerin (BCG) dependent on preferred brand of BCG by participating institution. Either 2-8 x 10^8 CFU for OncoTICE or, 81mg for ImmuCYST and TheraCys. Prior to treatment commencement, investigators should nominate which BCG brand will be used. The same brand of BCG must be used for all treatment administered to an individual participant throughout the study.
Dosage of Mitomycin (MM) fixed at 40mg per instillation.
干预措施: Mitomycin (MM) (Drug)
Treatment (Arm A): Intravesical BCG
Induction (weekly x 6); and followed by Maintenance (monthly x 10) beginning 3 months after randomisation.
Dosage of Bacillus of Calmette-Guerin (BCG) dependent on preferred brand of BCG by participating institution. Either 2-8 x 10^8 CFU for OncoTICE or, 81mg for ImmuCYST and TheraCys. Prior to treatment commencement, investigators should nominate which BCG brand will be used. The same brand of BCG must be used for all treatment administered to an individual participant throughout the study.
干预措施: Bacillus of Calmette-Guerin (BCG) (Biological)
结局指标
主要结局
Disease free survival (death or recurrence)
时间窗: Up to 5 years
Measured from the date of randomisation until the date of disease recurrence, upper tract disease is first evident, or the date of death, or until the date last known to be alive and without disease recurrence. Assessed via cystoscopy.
次要结局
- Activity (Clear cystoscopy at 3 months)(At 3 months after patient randomised)
- Time to recurrence (recurrence)(Up to 5 years)
- Time to progression (disease progression)(Up to 5 years)
- Safety (Adverse events graded according to CTC AE V4.0)(Measured before day 1 of each instillation during treatment.)
- Health-Related Quality of Life(Up to 5 years from the date of randomisation)
- Overall survival time (death from any cause)(Up to 5 years)
- Treatment Completion(Measured at end of study treatment (12 months after patient randomized).)
- Marginal resource use(5 years after last patient randomized (or date last patient has died, whichever sooner).)