Can We Predict of the Response of High Risk Non Muscle Invasive Bladder Cancer Patients to Intravesical Bacillus Calmette-Guerin? The Role of Immunological Markers

Sponsor

Mansoura University (Other)

Overall Status

Completed

CT.gov ID

NCT04723121

Collaborator

(none)

204

Enrollment

Location

Arm

Actual Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Intravesical BCG is the mainstay adjuvant management of high risk NMIBC. Adequacy of immune system stimulation is the determinant factor for patient response to BCG. Immunological markers for BCG-response could be helpful for urologists especially in the era of BCG shortage.

Objectives: To assess the predictive performance of different immunological markers on BCG-response in high risk NMIBC BCG-naïve patients.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Diagnostic Test: Urine ELISA for immunological markers (IL-2 and IL-10) Diagnostic Test: Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis	N/A

Detailed Description

Background: Intravesical BCG is the mainstay adjuvant management of high risk NMIBC. Adequacy of immune system stimulation is the determinant factor for patient response to BCG. Immunological markers for BCG-response could be helpful for urologists especially in the era of BCG shortage.

Objectives: To assess the predictive performance of different immunological markers on BCG-response in high risk NMIBC BCG-naïve patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

204 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Can We Predict of the Response of High Risk Non Muscle Invasive Bladder Cancer Patients to Intravesical Bacillus Calmette-Guerin? The Role of Immunological Markers

Actual Study Start Date :

Mar 1, 2013

Actual Primary Completion Date :

May 1, 2019

Actual Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: High risk NMIBC Patients with primary or recurrent NMIBC for whom primary TURBT was done and intravesical BCG was administered	Diagnostic Test: Urine ELISA for immunological markers (IL-2 and IL-10) IL-2 and IL-10 levels were measured in the supernatants. Natural human-produced IL-2 and IL-10 concen¬trations were determined in the urine of all patients and controls by solid phase ELISA Quantikine IL-2 Immunoassay and IL-10 Immunoassay, respectively Diagnostic Test: Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis blood samples using QIAamp® RNA Blood Mini kit (QIAGEN, USA). 1 μg of total RNA was reverse transcribed with random primers, using High Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA, USA). RT-qPCR analysis was carried out with SYBER Green PCR Master Mix (Applied Biosystems, Foster City, CA, USA). Primers for TNF-α, CTLA4, T-bet+, GATA3+, FoxP3+ and GABDH as PCR control

Arm

Intervention/Treatment

Other: High risk NMIBC

Patients with primary or recurrent NMIBC for whom primary TURBT was done and intravesical BCG was administered

Diagnostic Test: Urine ELISA for immunological markers (IL-2 and IL-10)

IL-2 and IL-10 levels were measured in the supernatants. Natural human-produced IL-2 and IL-10 concen¬trations were determined in the urine of all patients and controls by solid phase ELISA Quantikine IL-2 Immunoassay and IL-10 Immunoassay, respectively

Diagnostic Test: Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis

blood samples using QIAamp® RNA Blood Mini kit (QIAGEN, USA). 1 μg of total RNA was reverse transcribed with random primers, using High Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA, USA). RT-qPCR analysis was carried out with SYBER Green PCR Master Mix (Applied Biosystems, Foster City, CA, USA). Primers for TNF-α, CTLA4, T-bet+, GATA3+, FoxP3+ and GABDH as PCR control

Outcome Measures

Primary Outcome Measures

Initial BCG complete response [3 months]
free cystoscopy/negative cytology at 3 months.
Recurrence [1 year]
Recurrence is defined as development of new tumor/positive cytology in patients with ICR
Progression [1 year]
persistent/recurrent tumor during or after treatment with increasing tumor grade or upstaging to muscle invasion after initial complete response