A Prospective, Open, Single-center Clinical Study of Disitamab Vedotin Combined With BCG Therapy in HER2-expressing High-risk Non-muscle Invasive Bladder Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Percentage of Participants With CR as Assessed by the Investigator according to Cystoscopy and Urine Cytology at Month 3
研究概览
简要总结
This is a prospective, open, single-center clinical study of the anti-HER2(Human epidermal growth factor receptor-2) ADC(antibody-drug conjugate) drug Disitamab Vedotin in combination with BCG(bacillus Calmette-Guerin) therapy in very high-risk NMIBC(Non-muscle invasive bladder cancer) patients with HER2 expression (IHC 1+/2+/3+), which is being conducted in accordance with the Good Clinical Practice for Pharmaceutical Trials (GCP). Approximately 20 subjects will be enrolled in this study to evaluate the efficacy and safety of Disitamab Vedotin (2.0 mg/kg, administered intravenously every three weeks) in combination with BCG therapy.
详细描述
The study will include patients with very high risk NMIBC with HER2 expression (IHC 1+/2+/3+) who refuse to undergo cystectomy or do not meet the requirements for cystectomy. Reasons for unsuitability or refusal of cystectomy will be documented on an electronic case report form (eCRF).
Subjects will receive 6 months of Disitamab Vedotin therapy and at least 1 year of BCG therapy. EFS(Event free survival) and CR(Complete response) rates will be evaluated after treatment by cystoscopy, pathologic histology, urine cytology, laboratory tests, and imaging. Cystoscopy and urine cytology every three months for two years, and radiography every six months. Cystoscopy and urine cytology were done every six months and radiography once a year after two years.
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
- •1. Age≥18 years;
- •2. Histologically confirmed non-muscle-invasive urothelial cell carcinoma (UCC) of the bladder; A.Histopathology: any variant of UCC, The presence of any lymphovascular infiltration (LVI) was considered evidence of high risk. B. Confined to the mucosal (Ta, Tis) and lamina propria layers (T1) of the bladder. In addition, subjects had all visible tumors removed as completely as possible prior to the first dose of study drug and documented at baseline cystoscopy. C. CIS(Carcinoma in situ) does not require complete resection, but coexisting papillary carcinoma must be removed as completely as possible prior to enrollment and documented at baseline cystoscopy. Negative urine cytology results against malignant tumor cells are not required.
- •3. Presence of HER2 expression (IHC 1+/2+/3+) by IHC in our pathology department;
- •4. VHR(Very high risk) NMIBC, defined as having at least 1 of the following: Multiple and/or large (greater than \[\>\] 3 centimeters \[cm\]) T1, (HG/G3) tumors; T1, (HG/G3) tumor with concurrent CIS; T1, G3 with CIS in prostatic urethra; Micropapillary variant of non-muscle invasive urothelial carcinoma;
- •5. Received first dose of medication ≤ 12 weeks from first TURBT;
- •6. Refusal or unsuitability for radical cystectomy;
- •7. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (\/=30 milliliters per minute (mL/min) (calculated using the Cockcroft-Gault formula);
- •9. Subjects (or their legal representatives) must sign an informed consent form (ICF);
- •10. Females of childbearing potential must have a negative pregnancy test result (beta-hCG) (urine or serum) within 7 days prior to the first dose of study drug.
排除标准
- •Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancer;
- •Upper urinary tract urothelial carcinoma(UTIC), except 2 years without recurrence after previous radical UTUC;
- •Histopathologic examination reveals any small cell component of the bladder, simple adenocarcinoma, simple squamous cell carcinoma or simple squamous CIS;
- •Previously received other anti-HER-2 therapy;
- •Active malignancy outside of the disease being treated by the study (i.e., disease progression or need for change in therapy within the past 24 months);Only the following special cases are allowed: a. Skin cancer treated within the last 24 months and completely cured; b. Adequately treated lobular carcinoma in situ (LCIS) and ductal CIS; c. History of localized breast cancer and receiving anti-hormonal drugs or history of localized prostate cancer (N0M0) and receiving androgen blockade therapy.
- •History of uncontrolled cardiovascular disease, Included: 1) presence of any of the following in the past 3 months: unstable angina, myocardial infarction, ventricular fibrillation, torsional ventricular tachycardia, cardiac arrest or known congestive New York Heart Association class III-IV heart failure, cerebrovascular accident, or transient ischemic attack. 2) Prolonged QTc intervals confirmed by ECG evaluation during screening(Fridericia; QTc>480 ms). 3) Pulmonary embolism or other venous thromboembolism within the past 2 months.
- •Pregnant or lactating women;
- •Known infection with human immunodeficiency virus (HIV), unless the subject has been on stable antiretroviral therapy for the past 6 months or longer and has not had an opportunistic infection in the past 6 months and has had a CD4 count >350 in the past 6 months;
- •Evidence of active hepatitis B or C infection (e.g., subjects with hepatitis B who have a history of hepatitis C but have a normal polymerase chain reaction test result for hepatitis C virus and who are positive for antibodies to hepatitis B surface antigen may be enrolled in the study);
- •Have not recovered from toxic effects of previous anticancer therapy (except for toxic effects of no clinical significance, such as alopecia, skin discoloration, neuropathy and hearing impairment).
- •Delayed wound healing, defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or non-healing incisions;
- •Major surgery within 4 weeks prior to day 1 of cycle 1 (TURBT not considered major surgery);
- •Other patients assessed by the investigator to be unsuitable for participation in this study.
研究组 & 干预措施
RC48+BCG
Disitamab Vedotin (2.0 mg/kg, administered intravenously every three weeks); BCG therapy: Induction therapy, i.e., intravesical therapy once a week for 6 weeks. maintenance therapy, i.e., one course of maintenance therapy at three, six and twelve months after surgery, each course once a week for 3 weeks.
干预措施: Bacillus Calmette Guerin Vaccine (Drug)
RC48+BCG
Disitamab Vedotin (2.0 mg/kg, administered intravenously every three weeks); BCG therapy: Induction therapy, i.e., intravesical therapy once a week for 6 weeks. maintenance therapy, i.e., one course of maintenance therapy at three, six and twelve months after surgery, each course once a week for 3 weeks.
干预措施: Disitamab vedotin (Drug)
结局指标
主要结局
Percentage of Participants With CR as Assessed by the Investigator according to Cystoscopy and Urine Cytology at Month 3
时间窗: up to 3 months
CR at the 3-month disease assessment, evaluated by both cystoscopy and cytology.
Event-Free Survival (EFS) rate, as Assessed according to Cystoscopy and Urine Cytology
时间窗: up to 6 months
Percentage of Participants With Event-Free Survival (EFS), as assessed according to Cystoscopy and Urine Cytology ( patients who are alive and free of persistent/recurrent high-grade NMIBC.)
次要结局
- Overall Survival(Time from date of randomization to death from any cause, assessed up to 60 months)
- Percentage of Participants With Event-Free Survival (EFS), as Assessed according to Cystoscopy and Urine Cytology(up to 24 months)
- Duration of CR will be defined for participants with a CR as the time from the first occurrence of a documented complete response to recurrence of high-grade NMIBC or death from any cause.(From first occurence of a documented CR until the time of recurrence of NMIBC or death from any cause, whichever came first, assessed up to 24 months)
- Progression-Free Survival (PFS), as Assessed according to Cystoscopy and Urine Cytology(Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- Percentage of Participants With Adverse Events(up to 24 months)
- Percentage of Participants With CR as Assessed by the Investigator according to Cystoscopy and Urine Cytology at Month 6, 12(up to 12 months from the date of randomization as assessed by the investigator according to cystoscopic assessment and urine cytology)
研究者
Ding-Wei Ye
Clinical Professor
Fudan University