Low Energy Shock Wave Therapy and Non-Muscle Invasive Bladder Cancer

Study of the Effect of Neoadjuvant Low Energy Shock Wave Therapy on Non-Muscle Invasive Bladder Cancer: A Preliminary Pilot Controlled Clinical Trial

The investigators hypothesize that low energy shock wave therapy (LESW) might induce damage to the tumor tissues of non-muscle invasive bladder cancer (NMIBC), so they could be ablated and detached from the surface.

The patients who are suffering from NMIBC will be randomly allocated into two groups: The first group (control group): 25 patients will be exposed to sham treatment before transurethral resection of bladder tumor (TURBT) without using LESW therapy. The second group (LESW group): 25 patients will be exposed to LESW therapy before TURBT.

The apoptotic effect of LESW will be studied via histopathological examination and molecular studies of the resected bladder tissues.

The patients will receive intravesical chemotherapy or BCG immunotherapy and they will be followed up at outpatient clinic for two years by MRI, outpatient cystoscopy and cytology to identify the recurrence and progression rate of NMIBC.

Study Overview

• Status: Recruiting
• Conditions: Non-Muscle Invasive Bladder Cancer
• Intervention / Treatment: Device: Low Energy Shock Wave Treatment; Device: Sham Treatment

Detailed Description

The investigators hypothesize that low energy shock wave therapy (LESW) might induce damage to the tumor tissues of non-muscle invasive bladder cancer (NMIBC), so they could be ablated and detached from the surface.

The patients who are suffering from NMIBC will be randomly allocated into two groups: The first group (control group): 25 patients will be exposed to sham treatment before transurethral resection of bladder tumor (TURBT) without using LESW therapy. The second group (LESW group): 25 patients will be exposed to LESW therapy before TURBT. The shock wave applicator (Dornier AR2, shock wave device, Dornier MedTech 2010, Wessling, Germany) will be gently placed directly on the ultrasound transmission gel over the skin surface of the suprapubic region above the urinary bladder at the site of the papillary lesion (US guided) and at other five points. Points 1 and 2 will be at the level of transverse crease 2 cm above the pubic bone and 5 cm from each, points 3 and 4 will 2 cm above points 1 and 2, and point 5 will be centered of points 1-4. A total of 2000 pulses at 0.25 mJ/mm2 will be delivered with a frequency of 3 pulses per second. The position of the shock wave applicator will be changed after every 400 pulses.

The apoptotic effect of LESW will be studied via histopathological examination for the type of bladder tumor, pathological stage, grade, association of carcinoma in situ and morphological features of apoptosis in terms of compaction of the nuclear chromatin (pyknosis), loss of cellular volume and chromatin condensation on the nuclear envelope (nuclear crescents), Immunohistochemical analysis of anti-caspase-3 antibody and molecular studies of Bax (an apoptotic promotor), BCL-2 and Survivin (apoptotic inhibitors) Relative Gene Expression in the resected bladder tissues.

The patients will receive intravesical chemotherapy or BCG immunotherapy and they will be followed up at outpatient clinic for two years by MRI, outpatient cystoscopy and cytology to identify the recurrence and progression rate of NMIBC.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ahmed Mosbah; Phone Number: +201062525591; Email: amosbah64@yahoo.com

Study Locations

• Egypt
  • Mansoura, Egypt
    • Recruiting
    • Urology and nephrology center, Mansoura University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with ≤ T1, de novo, single and small (<3cm) papillary lesions will be included in the study.

Exclusion Criteria:

• Patients with ≥ T2 bladder cancer, evidence of nodal metastasis, associated upper tract urothelial carcinoma, morbidly obese patients, patients with absolute contraindication for shock wave therapy or those who refuse will be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LESW group; The shock wave applicator (Dornier AR2, shock wave device, Dornier MedTech 2010, Wessling, Germany) will be gently placed directly on the ultrasound transmission gel over the skin surface of the suprapubic region above the urinary bladder at the site of the papillary lesion (ultrasound guided) and at other five points. Points 1 and 2 will be at the level of transverse crease 2 cm above the pubic bone and 5 cm from each, points 3 and 4 will 2 cm above points 1 and 2, and point 5 will be centered of points 1-4. A total of 2000 pulses at 0.25 mJ/mm2 will be delivered with a frequency of 3 pulses per second. The position of the shock wave applicator will be changed after every 400 pulses.	Device: Low Energy Shock Wave Treatment; The shock wave applicator (Dornier AR2, shock wave device, Dornier MedTech 2010, Wessling, Germany) will be gently placed directly on the ultrasound transmission gel over the skin surface of the suprapubic region above the urinary bladder at the site of the papillary lesion (ultrasound guided) and at other five points. Points 1 and 2 will be at the level of transverse crease 2 cm above the pubic bone and 5 cm from each, points 3 and 4 will 2 cm above points 1 and 2, and point 5 will be centered of points 1-4. A total of 2000 pulses at 0.25 mJ/mm2 will be delivered with a frequency of 3 pulses per second. The position of the shock wave applicator will be changed after every 400 pulses.
SHAM_COMPARATOR: Control group; This group of patients will be exposed to the same therapy head, which will also be fitted with a stand-off without energy transmission.	Device: Sham Treatment; The patients will be exposed to the same therapy head, which will also be fitted with a stand-off without energy transmission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression survival.	2 years
Recurrence-free survival.	2 years

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Study Director: Ahmed Mosbah, Urology and Nephrology Center, Mansoura University, Egypt

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 28, 2020
• Primary Completion (ANTICIPATED): November 28, 2022
• Study Completion (ANTICIPATED): November 28, 2023

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: November 24, 2020
• First Posted (ACTUAL): November 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: NMIBC; LESW; TURBT
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: LESW-NMIBC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no current plan for whether to share IPD or not.

Drug and device information, study documents

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