A Phase Ib Trial of Intravesical Photodynamic Therapy in Patients With Non-muscle Invasive Bladder Cancer at High Risk of Progression Who Are Refractory to Bacillus Calmette-Guerin Therapy and Who Are Medically Unfit for/Refuse Cystectomy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Safety Analysis of TLD1433 and PDT assessed with the incidence and severity of Adverse Effects.
研究概览
简要总结
This is a phase Ib, open-label, single-arm, single-center study conducted in Canada. Subjects with NMIBC (Ta, T1, and/or Tis) who are not candidates for or have refused radical cystectomy will be eligible for participation in the study. Bacillus Calmette-Guerin (BCG) intolerance or refractory disease are defined as inability to tolerate or failure to achieve a tumour-free state after at least one induction (a minimum of 5 instillations) followed by either a second induction (a minimum of 5 instillations) or at least 2 maintenance instillations. Subjects experiencing disease relapse within 12 months or less after finishing the second course of BCG therapy are also considered refractory. The study will consist of 2 phases. In the first phase, 3 subjects will receive PDT (TLC-3200 System) employing 0.35 mg/cm^2 (maximum recommended starting dose) TLD1433. If treatment with the maximum recommended starting dose does not raise significant safety concerns as determined by the safety monitoring committee, an additional 6 subjects will receive PDT with 0.70 mg/cm^2 (therapeutic dose) TLD1433.
详细描述
10.1 Overall Study Design and Plan: Description
This is a phase Ib, open-label, single-arm, single-center study conducted in Canada. Subjects with NMIBC (Non-muscle Invasive Bladder Cancer, Ta, T1, and/or Tis) who are not candidates for or have refused radical cystectomy will be eligible for participation in this study. BCG intolerance or refractory disease are defined as inability to tolerate or failure to achieve a tumour-free state after at least one induction (a minimum of 5 instillations) followed by either a second induction (a minimum of 5 instillations) or at least 2 maintenance instillations. Subjects experiencing disease relapse within 12 months or less after finishing the second course of BCG therapy are also considered refractory.
The study will consist of 2 phases. In the first phase, 3 subjects will receive PDT employing 0.35 mg/cm^2 (maximum recommended starting dose) TLD1433 and 90 J/cm^2 of green light delivered by TLC-3200. If treatment with the maximum recommended starting dose does not raise significant safety concerns as determined by the safety monitoring committee, an additional 6 subjects will receive PDT with 0.70 mg/cm^2 (therapeutic dose) TLD1433 and 90 J/cm^2 of green light delivered by TLC-3200.
10.2 Screening Period
Subjects will be qualified for study entry by review of inclusion and exclusion criteria during the Screening Period, which will last up to 2 weeks.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be > 18 years of age on day of signing informed consent.
- •Have histologically confirmed NMIBC (T1, Ta, and/or Tis) according to the 2004 World Health Organization (WHO) classification within 8 weeks prior of treatment initiation. Participants with tumours of mixed transitional / non-transitional cell histology are eligible, but urothelial carcinoma must be the predominant histology. Participants with predominant or exclusively non-urothelial histology are not eligible. Confirmation of histology, grade and stage will be performed by local review and must be completed prior to enrolment.
- •For participants with Ta and T1, they must have undergone complete TURBT defined as absence of resectable disease after at least 2 cystoscopy / TURBT procedures. The most recent cystoscopy must have been performed no longer than 8 weeks prior to the first dose of trial treatment.
- •Have been considered intolerant or refractory to first-line BCG therapy defined as inability to tolerate or failure to achieve a tumour-free state after at least one induction (minimum of 5 instillations) followed by at either a second induction (minimum of 5 instillations) or at least 2 maintenance instillations. Participants experiencing disease relapse within 12 months or less after finishing the second course of BCG therapy are also considered refractory.
- •Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.
- •Have a performance status of 70 or more on the Karnofsky Performance Status Scale as assessed within 28 days prior to treatment initiation.
- •Have no evidence of upper urothelial carcinoma (involving the upper urinary tract or the urethra) (confirmed by staging to exclude extravesical disease, which may include radiological imaging and/or biopsy) within 3 months of treatment initiation. If previous work up occurred more than 3 months prior to treatment initiation, staging for extravesical disease must be repeated prior to enrolment in order to determine eligibility.
- •Have satisfactory bladder function. Ability to retain instillate for a minimum of 1 hour, even with premedication.
- •Are available for the duration of the study including follow-up (approximately 12 months).
- •Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Female participants of childbearing potential must be willing to use 2 methods of birth control (oral contraceptive, pills, diaphragm, or condoms) or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
- •Male participants must agree to use an adequate method of contraception (oral contraceptive, pills, diaphragm, or condoms) starting with the first dose of study therapy through 120 days after the last dose of study therapy.
排除标准
- •Past or current muscle invasive (i.e., T2, T3, T4) or metastatic urothelial carcinoma.
- •Has concurrent extravesical (i.e. urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
- •Have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower; Prostate-Specific Antigen undetectable for 5 years while off androgen deprivation therapy.
- •Have a known psychiatric or substance abuse disorder that would interfere with meeting the requirements of the trial.
- •Have a history or current evidence of any condition, therapy, surgery or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the participant's participation in the trial, or is not in the best interest of the participant to participate.
- •Currently receiving any photosensitizing medications.
- •Have a known hypersensitivity to ruthenium.
- •Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1, Prohibited Medications).
- •Participated in a study with an investigational agent or device within 3 months from the first dose of current study treatment.
- •Prior treatment with an intravesical chemotherapeutic agent within 3months of the first dose of current study drug, with the exception of a single perioperative dose of chemotherapy immediately post-TURBT (not considered treatment).
- •Have an active infection requiring systemic therapy, including active or intractable urinary tract infection (UTI), in the last month.
- •Has any contraindication to general or spinal anesthesia.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
- •Known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
- •Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., hepatitis C virus (HCV) RNA [qualitative] is detected).
- •Received a live virus vaccine within 30 days of planned start of trial treatment.
- •Have a diagnosis of psoriasis.
研究组 & 干预措施
0.35 mg/cm^2 TLD1433 Bladder Dose
TLD1433 infusion and photodynamic therapy treatment (PDT):
TLD1433 is infused for 1 hour and photodynamic therapy treatment is performed after TLD1433 has been rinsed from the bladder. If treatment with the maximum recommended starting dose of 0.35mg/cm^2 does not raise significant safety concerns as determined by the safety monitoring committee, the therapeutic dose of TLD1433 (0.70mg/cm^2) will be used.
干预措施: TLD1433 infusion and photodynamic therapy (PDT) treatment (Drug)
结局指标
主要结局
Safety Analysis of TLD1433 and PDT assessed with the incidence and severity of Adverse Effects.
时间窗: Up to the completion of follow-up phase (180 days)
Adverse events (AE) summaries will be provided showing the number and percentage of participants who experienced at least 1 AE. These summaries will be presented by body system and preferred term. Severe AEs (SAEs) and AEs resulting in discontinuation will be summarized separately in a similar fashion.
次要结局
- Pharmacokinetic Analysis(Blood (prior to drug, 1h, 4h, 8h, 24h, and 72h post drug). Urine (prior to drug, 8h, 24h, and 72h post drug))