Pilot Study of External Hyperthermia and Intravesical Mitomycin-C To Treat Recurrent Bladder Cancer After Resection and Standard Adjuvant Therapy
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Safety and Tolerability
研究概览
简要总结
Hypothesis: In selected patients external hyperthermia will be used in combination with intravesical Mitomycin-C (MMC) to treat recurrent transitional cell carcinoma (TCC) of the bladder after local resection and standard adjuvant therapy and thus prevent or delay recurrence and the need for radical cystectomy.
详细描述
It is well established that tumor cells are sensitive to heat and when combined with a chemotherapeutic agent, drug uptake and intracellular distribution of drug within malignant cells is improved due to increased cellular permeability. Further, hyperthermia inhibits deoxyribonucleic acid (DNA) repair as a result of increased reaction between DNA and chemotherapy. By heating bladder tissue and accelerating the necessary series of reactions to link agents such as mitomycin C to cell DNA, this effect may be optimized. Depending on the extent of resection (and location, size, and depth of invasion of remaining tumor) after transurethral resection of the bladder tumor(TURBT), recommended adjuvant therapy consists of intravesical chemotherapy. MMC has been studied at doses as high as 80 mg without producing significant or irreversible side effects. The most commonly used dose of mitomycin is 40 mg.2
This pilot study proposes to use Mitomycin C at a dose of 40 mg in conjunction with deep hyperthermia to enhance the effect intravesical chemotherapy as second-line treatment of recurrent TCC (Stage Ta, T1, or Tis) of the bladder after surgical resection and standard adjuvant therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-muscle invasive transitional cell carcinoma (TCC) of the bladder (Ta, T1, Tis) recurrent after initial surgery and at least one round of adjuvant treatment (i.e. 6 weeks of intravesical biological therapy with Bacillus Calmette Guerin (BCG) solution); or
- •An inability to tolerate BCG
- •Age > 18
- •Eastern Cooperative Oncology Group(ECOG) Performance Status 0-2
- •Laboratory tests performed within 14 days of study enrollment:
- •Leukocytes ≥ 3,200, Absolute Neutrophil count ≥ 1,500, Platelets ≥ 100,000
- •Hemoglobin ≥ 9.0 gm/dL, Total bilirubin ≤ institution upper limit of normal *(ULN), Asparate Aminotransferase(AST) and Alanine Aminotransferase(ALT) ≤ 2.5 times ULN, Alkaline phosphatase ≤ 2.5 times ULN
- •Creatinine ≤ 1.5 times ULN
- •Women of child bearing potential must have a negative pregnancy test
- •If post-menopausal - Amenorrhea for ≥ 12 months
排除标准
- •Pregnancy or breastfeeding
- •Muscle invasive disease (T2-T4)
- •Prior radiation to the pelvis
- •Peripheral neuropathy (any grade)
- •Thrombocytopenia, coagulation disorder or an increase in bleeding tendency due to other causes
- •Known bladder fistula
- •Hypersensitive or idiosyncratic reaction to mitomycin-C or its components in the past
研究组 & 干预措施
Hyperthermia system, Mitomycin C
Pilot study single arm study to test the safety, tolerability and clinical benefit of regional hyperthermia and mitomycin-C intravesical chemotherapy to treat non-invasive Transitional Cell carcinoma (TCC) of the bladder that has recurred after standard resection and adjuvant therapy.
干预措施: Hyperthermia System (Device)
Hyperthermia system, Mitomycin C
Pilot study single arm study to test the safety, tolerability and clinical benefit of regional hyperthermia and mitomycin-C intravesical chemotherapy to treat non-invasive Transitional Cell carcinoma (TCC) of the bladder that has recurred after standard resection and adjuvant therapy.
干预措施: Mitomycin C (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: During Treatment Phase average 6 weeks
Number of patient treatments stopped due to safety concerns or treatment intolerability. All events below are grade 1/2 toxicity. No grade 3-5 toxicity was observed.
次要结局
- Median Recurrence Free-survival(Median follow-up 3.18 years)
研究者
Mark Dewhirst
Professor
Duke University