HIVEC in Patients With Non-Muscle-Invasive Bladder Cancer

A Multicenter Prospective Randomized Controlled Clinical Trial of Hyperthermic Intravesical Chemotherapy After Transurethral Resection of Bladder Tumors in Patients With Non-Muscle-Invasive Bladder Cancer

The purpose of this study is to determine the efficacy and safety of Hyperthermic Intravesical Chemotherapy (HIVEC) with Gemcitabine (GEM) after Transurethral Resection of Bladder Tumors (TURBT) in the treatment of medium or high-risk group Non-Muscle-Invasive Bladder Cancer (NMIBC).

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Muscle-Invasive Bladder Cancer
• Intervention / Treatment: Procedure: TURBT; Procedure: Intravesical Chemotherapy; Drug: Gemcitabine; Procedure: HIVEC

Detailed Description

In this study, patients with Non-Muscle-Invasive Bladder Cancer (NMIBC) and planed to undergo Transurethral Resection of Bladder Tumors (TURBT) are randomized into HIVEC group and control group. In HIVEC group, HIVEC is performed with Gemcitabine Gemcitabine (3g/150ml NS) at 45 °C for 60 minutes within 4 weeks, once a week (±5 days) for 6 to 8 times, once a month to 1 year. For the patients in the control group, Intravesical Chemotherapy is administered after TURBT. The primary endpoint is 2-year recurrence rate. Secondary end points include 1-year recurrence rate, recurrence-free survival (RFS) rate, disease free survival (DFS) rate, time to treatment failure (TTF), Success rate of therapeutic operation, Instrument performance evaluation, quality of international prostate symptom score, quality of Urinary Symptoms Distress Score. All efficacy analyses are conducted in the intention-to-treat population. Safety analysis include only patients who receive their randomly assigned treatment.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shuzhong Cui, MD; Phone Number: 020-66673666; Email: cuishuzhong@gzhmu.edu
• Study Contact Backup: Name: Jing Li, MD; Phone Number: 020-66673666; Email: lijingzlyy@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients who did not receive induction perfusion within 4 weeks after complete resection of bladder tumor with TURBT (Patients who were judged by the investigator to be in need of secondary electrotomy, for the last time).
2. Recurrence risk and prognosis of Non-Muscle-Invasive Bladder Cancer were divided into medium-risk group or high-risk group (patients who underwent multiple electrosurgical biopsies, and the pathological results were based on higher grade tumors).
3. KPS score ≥80, expected survival > 30 months.
4. Pathological suggested non-myoinvasive urothelial carcinoma of the bladder.
5. Age between 18 and 70 years, all genders.
6. Volunteer to participate in this clinical trial and written informed consent.

Exclusion Criteria:

1. Patients with bladder cancer in situ.
2. Combined with proven upper urinary tract or urethral tumors.
3. The patients were complicated with bladder perforation, gross hematuria or urinary tract infection of grade 3-4.
4. Patients with urethral discontinuity, urethral stricture, or inability to use a three lumen catheter normally affect perfusion therapy.
5. Patients who had undergone partial cystectomy or abnormal bladder structure were judged by the investigator to be unsuitable for perfusion therapy.
6. Patients with severe coagulation dysfunction.
7. A history of allergy to injected drugs (gemcitabine).
8. History of pelvic radiation, systemic chemotherapy, or immunotherapy.
9. Complicated with cardiovascular, cerebrovascular, hematopoietic, immune system and other serious diseases.
10. Patients with mental illness, substance abuse, alcoholism, and inability to cooperate.
11. Breastfeeding, pregnant, or planning to have a baby in the near future.
12. Recurrent patients with a prior history of BCG or bladder thermoperfusion therapy.
13. Participated in other clinical trials 1 month before the trial.
14. Vesicoureteral regurgitation.
15. The investigator considered it inappropriate to participate in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Matched control; Patients undergo Transurethral Resection of Bladder Tumors (TURBT) and receive Intravesical Chemotherapy.	Procedure: TURBT; Transurethral Resection of Bladder Tumors; Procedure: Intravesical Chemotherapy; Intravesical Chemotherapy with Gemcitabine (3g/150ml NS). Induction perfusion was required to start within 4 weeks, once a week (±5 days) for 6 to 8 times. After the last induction infusion, maintenance infusion was performed, once every month (±2 weeks) for 1 year from the first induction infusion.; Drug: Gemcitabine; Gemcitabine (3g/150ml NS).
Experimental: HIVEC; Patients undergo Transurethral Resection of Bladder Tumors (TURBT) and Hyperthermic Intravesical Chemotherapy (HIVEC)	Procedure: TURBT; Transurethral Resection of Bladder Tumors; Drug: Gemcitabine; Gemcitabine (3g/150ml NS).; Procedure: HIVEC; Hyperthermic Intravesical Chemotherapy with Gemcitabine (3g/150ml NS) at 45 °C for 60 minutes. Induction perfusion was required to start within 4 weeks, once a week (±5 days) for 6 to 8 times. After the last induction infusion, maintenance infusion was performed, once every month (±2 weeks) for 1 year from the first induction infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate	The patients were observed for 2 years since they received HIVEC or intravesical chemotherapy，and cystoscopy was repeated every 3 months. If a new tumor-like organism is seen under the microscope, and pathology indicates urothelial carcinoma of the bladder after TURBT or cystoscopic biopsy, the tumor is considered to have recurred. 2-year recurrence rate = number of recurrence cases within 2 years / total number of enrolled cases * 100%.	2-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year recurrence rate	1-year recurrence rate = number of recurrence cases within 1 years / total number of enrolled cases * 100%.	1-year
Recurrence-free survival (RFS) rate	Recurrence free survival is calculated from the date of randomization to the date of record recurrence or death from any cause, whichever occurred first.	2-year
Time to treatment failure	Time to treatment failure is calculated from the date of randomization to the date of treatment discontinuation/termination, including any reason for discontinuation/termination, such as disease progression, death, withdrawal due to adverse events, subject's refusal to continue the study, or use of a new treatment.	2-year
Success rate of therapeutic operation	Success rate of therapeutic operation	2-year
Quality of international prostate symptom score	IPSS is International Prostate Symptom Score (IPSS), 0~35, the higher the score, the worse the symptom severity is.	Evaluation was performed during the screening period and at 3, 12 and 24 months after initiation of treatment.
Quality of bother of score	BS is Bother of Score (BS), 0~6, the higher the score, the worse the performance is.BS is the Bother of Score (BS), 0~6, the higher the score, the worse the performance is.	Evaluation was performed during the screening period and at 3, 12 and 24 months after initiation of treatment

Collaborators and Investigators

• Sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Investigators: Principal Investigator: Shuzhong Cui, MD, Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: March 7, 2024
• First Submitted That Met QC Criteria: March 18, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: recurrence rate; Non-Muscle-Invasive Bladder Cancer; Hyperthermic Intravesical Chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: HIVEC(PRG)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No