Blue Laser -5ala Photodynamic Therapy (PDT) in High-Risk Non-muscle Invasive Bladder Cancer (NMIBC) Patients

Non-muscle-invasive Bladder Cancer Clinical Trial

— BL-PDT-RCT  

Official title:

A Prospective, Multicenter, Randomized Controlled Clinical Study of Blue Laser-5ALA-photodynamic Therapy (PDT) in the Prevention of Postoperative Tumor Recurrence in High-risk Non-muscle-invasive Bladder Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05547516
• Other study ID #: 2021ZDLSF02-16
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 13, 2022
• Est. completion date: February 1, 2024

Study information

• Verified date: September 2022
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: Dalin He, Dr.
• Phone: 13991288221
• Email: hedl[@]mail.xjtu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This project will conduct a large-sample, multi-center prospective clinical trial to further establish the safety and efficacy of BL-5ALA-PDT in preventing Non-Muscle Invasive Bladder Cancer (NMIBC) recurrence when compared to the usual postoperative perfusion chemotherapy regimen.

Description:

This project will conduct a large-sample, multi-center prospective clinical trial to further establish the safety and efficacy of BL-5ALA-PDT in preventing Non-Muscle Invasive Bladder Cancer (NMIBC) recurrence when compared to the usual postoperative perfusion chemotherapy regimen.

Detailed Description:

1. Overall Study Design and Plan: a multicenter prospective randomized controlled clinical study;

2. Research steps: clinical recruitment, random enrollment, surgical treatment, regular postoperative preventive adjuvant intervention treatment + follow-up observation, and statistical analysis.

3. Screening Period: After obtaining the consent of the hospital ethics committee, the recruitment advertisement will be published to start the recruitment. September 1, 2022 to February 28, 2023, with at least one year follow-up. By reviewing inclusion and exclusion criteria, patients will be eligible to participate in the study. A total of 140 patients were recruited: 70 patients received conventional postoperative infusion chemotherapy (control group), and 70 patients received conventional postoperative infusion chemotherapy combined with BL-5ALA-PDT (BL-5ALA-PDT group).

4. Study Drug and PDT Administration: TURB-t uses the plasma resectoscope produced by Japan Olympus Company, and uses standardized layered electric resection or laser ablation surgical techniques; BL-5ALA-PDT uses Xi'an Lanji Medical Electronic Technology Co., Ltd. (The semiconductor laser therapeutic apparatus produced by Xi'an) was used as the PDT excitation light source, and 5ALA was purchased from Shanghai Fudan-zhangjiang Bio-Pharmaceutical Co., Ltd.

5. Postoperative infusion treatment plan: standard infusion chemotherapy (including gemcitabine, mitomycin, epirubicin, etc.), dissolved in 50 mL of normal saline or glucose, and intravesical infusion chemotherapy for 60 minutes. Perfusion can be done within 24 hours after operation, then once a week, a total of 8 times, and then changed to once a month to 12 months after operation; BL-5ALA-PDT program: 1.5g of 5ALA (Shanghai Fudan-zhangjiang Bio-Pharmaceutical Co., Ltd) was dissolved in 50 mL of normal saline, and infused into the bladder for 2 hours before surgery and before each cystoscopy. Blue laser irradiation was carried out at 30mW/cm2 and 21min under irradiation. PDT was performed during the operation and at 3, 6, and 9 months after the operation.

6. Postoperative follow-up plan: review urine routine, urinary B-ultrasound and cystoscopy in at 3, 6, and 9 months after operation, and record the follow-up in the follow-up registry at the same time. Follow-up content: urine routine, urinary B-ultrasound and cystoscopy results.

7. Evaluation indicators:

Main Outcome: Tumor recurrence rate 1 year after surgery Secondary Outcome: Observe postoperative complications (focus on side effects beyond standard perfusion therapy)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: February 1, 2024
• Est. primary completion date: September 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Pathologically determined as high-risk NMIBC (meet any of the following: ?T1 stage tumor; ?G3 or high-grade urothelial carcinoma; ?CIS; cancer), patients planning to undergo transurethral surgery;

2. According to the EORTC score of 5 or above;

3. 18=age=80 years old, according to the requirements of the ethics committee, the patients (or authorized principals) agree to participate in this experiment and sign the informed consent.

Exclusion Criteria:

1. Patients with severe systemic diseases (such as severe coagulation disorders, decompensation of important organ functions) or chronic wasting diseases;

2. The patient has a history of other malignant tumors in the past five years;

3. Pregnant and lactating women;

4. Those who have undergone major surgery within 1 month before enrollment;

5. Participate in other clinical trials;

6. Other conditions (such as: mental illness, etc.) considered inappropriate by the researcher.

Related Conditions & MeSH terms

• Non-muscle-invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Standard infusion chemotherapy
standard infusion chemotherapy (including gemcitabine, mitomycin, epirubicin, etc.), dissolved in 50mL normal saline or glucose, intravesical infusion chemotherapy, retained for 60min. Perfusion can be performed within 24 hours after surgery, and then once a week for a total of 8 times, and then once a month until 12 months after surgery

Procedure:
• BL - 5 ala PDT
BL - 5 ala PDT - plan: 5ALA 1.5g (Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co.,Ltd), dissolved in 50mL normal saline, was infused into the bladder for 2 hours before surgery and before each cystoscopy. Blue laser irradiation was performed under a flexible cystoscope at 30mW/cm2 for 21min. PDT was performed during the operation and at 3, 6, and 9 months after the operation.

Locations

Country	Name	City	State
China	Dalin He	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University

Country where clinical trial is conducted

China, 

References & Publications (6)

Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, Hahn SM, Hamblin MR, Juzeniene A, Kessel D, Korbelik M, Moan J, Mroz P, Nowis D, Piette J, Wilson BC, Golab J. Photodynamic therapy of cancer: an update. CA Cancer J Clin. 2011 Jul-Aug;61(4):250-81. doi: 10.3322/caac.20114. Epub 2011 May 26. Review. — View Citation

Babjuk M, Burger M, Compérat EM, Gontero P, Mostafid AH, Palou J, van Rhijn BWG, Rouprêt M, Shariat SF, Sylvester R, Zigeuner R, Capoun O, Cohen D, Escrig JLD, Hernández V, Peyronnet B, Seisen T, Soukup V. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update. Eur Urol. 2019 Nov;76(5):639-657. doi: 10.1016/j.eururo.2019.08.016. Epub 2019 Aug 20. Review. — View Citation

Ericson MB, Grapengiesser S, Gudmundson F, Wennberg AM, Larkö O, Moan J, Rosén A. A spectroscopic study of the photobleaching of protoporphyrin IX in solution. Lasers Med Sci. 2003;18(1):56-62. — View Citation

Kushibiki T, Hirasawa T, Okawa S, Ishihara M. Blue laser irradiation generates intracellular reactive oxygen species in various types of cells. Photomed Laser Surg. 2013 Mar;31(3):95-104. doi: 10.1089/pho.2012.3361. Epub 2013 Feb 7. — View Citation

Messing EM, Tangen CM, Lerner SP, Sahasrabudhe DM, Koppie TM, Wood DP Jr, Mack PC, Svatek RS, Evans CP, Hafez KS, Culkin DJ, Brand TC, Karsh LI, Holzbeierlein JM, Wilson SS, Wu G, Plets M, Vogelzang NJ, Thompson IM Jr. Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial. JAMA. 2018 May 8;319(18):1880-1888. doi: 10.1001/jama.2018.4657. — View Citation

Railkar R, Agarwal PK. Photodynamic Therapy in the Treatment of Bladder Cancer: Past Challenges and Current Innovations. Eur Urol Focus. 2018 Jul;4(4):509-511. doi: 10.1016/j.euf.2018.08.005. Epub 2018 Aug 23. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor recurrence rate 1 year after surgery	The recurrence rate of NMBC at 1 year after surgery was evaluated by regular urine routine, urinary B-ultrasound and cystoscopy	from date of randomization until the date of first documented Tumor recurrence
Secondary	Observe postoperative complications (focus on side effects beyond standard perfusion therapy)	postoperative complications were evaluated by regular urine routine, urinary B-ultrasound and cystoscopy	from date of randomization until the date of first documented postoperative complications