Propranolol Adjuvant Treatment of Bladder Cancer

Propranolol Adjuvant Treatment of Bladder Cancer: a Randomized Phase II Clinical Trial

Bladder cancer (bladder cancer) is the tenth most common cancer in the world, ranking 13th in the number of deaths. There are about 549000 new cases of bladder cancer worldwide, with 200000 deaths and a higher incidence rate in men than in women. In 2013, the incidence rate of bladder cancer was high in China, accounting for 2.02% of all new cases. Bladder cancer has become a major disease threatening people's life and health. Therefore, the exploration of the mechanism of the occurrence and development of bladder cancer and effective drugs has been an important focus of bladder cancer research. The current treatment of bladder cancer is mainly TURBT (transurethral resection of bladder tumour) resection and BCG, chemotherapy adjuvant treatment, but its recurrence and metastasis still exist, so this study aims to explore an effective drug treatment. The purpose of this study was to investigate the safety and efficacy of propranolol in adjuvant BCG therapy, and whether propranolol can effectively alleviate the metastasis and recurrence of bladder cancer and improve the survival time after bladder cancer surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: BCG; Drug: Propranolol Hydrochloride

• Study Type: Interventional
• Enrollment (Anticipated): 242
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ages 18 to 75
2. Patients with pathologically confirmed non-muscle invasive bladder cancer (T1 / Ta high grade / CIS), according to the 2004 WHO classification criteria
3. No evidence of patients with muscular invasive disease
4. American Oncology Group ECOG score <2
5. Patients' expected survival time should be more than 3 months
6. Organ function and hematopoietic function must meet the following requirements: hemoglobin (HGB) ≥ 90g / L; white blood cell count (WBC) ≥ 3 × 10 ^ 9 / L; absolute neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L Platelet count (PLT) ≥100 × 10 ^ 9 / L; total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase ( ALT) ≤ 2.5 × ULN; if abnormal liver function is due to tumor liver metastasis, AST or ALT ≤ 5 × ULN; serum creatinine (Cr) ≤ 1.5 × ULN; international standardized ratio (INR) or plasma prothrombin time PT) ≤1.5 × ULN
7. Blood pressure with acceptable surgery: blood pressure greater than 90 / 60mmHg, resting heart rate greater than 60 beats / min
8. Volunteer to participate in clinical research; fully understand, inform, and sign the consent form; willing to follow and have the ability to complete all test procedures

Exclusion Criteria:

1. Contraindications for propranolol: bronchial asthma, cardiogenic shock, cardiac block (II-III degree Atrioventricular conduction block), severe or acute heart failure, sinus bradycardia
2. In use or have used any beta-blockers for disease reasons in the past two years
3. Patients with other malignancies within 5 years before enrollment, in addition to cervical carcinoma in situ and cured skin basal cell carcinoma with appropriate treatment
4. Immunodeficiency, such as patients with HIV infection or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation
5. Patients with tumor brain metastases and bone marrow metastases were excluded, and patients with liver metastases and lung metastases could be included
6. Participants who have participated in clinical studies of drugs other than BCG within 4 weeks
7. Patients with a history of allergy to propranolol
8. Alcohol, drug or substance abuse history in the past year
9. Subject has an active infection or an unexplained fever during screening, before the first dose> 38.5 degrees(According to the researcher's judgment, the subjects can be enrolled due to the fever caused by the tumor)
10. Any situation that the investigator believes may increase the risk of the subject or interfere with clinical trials

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: BCG; After TURBT, the first year: once a week for 6 times, from the 7th week, once every 2 weeks, and 3 times. Administer once a month starting from the 13th week and continue to give 10 times. Second and third years: once a month, 12 times a year.	Drug: BCG; Control group: BCG vaccine: After TURBT, the first year: once a week for 6 times, from the 7th week, once every 2 weeks, and 3 times. Administer once a month starting from the 13th week and continue to give 10 times. Second and third years: once a month, 12 times a year.
EXPERIMENTAL: Propranolol plus BCG; After TURBT administered for 2 consecutive years, oral propranolol, starting dose 10mg, tid, then 20mg, tid,lastly increased to 40mg, bid. After the last BCG infusion, propranolol was gradually reduced, in the order of 20 mg, tid to 10 mg, tid.	Drug: BCG; Control group: BCG vaccine: After TURBT, the first year: once a week for 6 times, from the 7th week, once every 2 weeks, and 3 times. Administer once a month starting from the 13th week and continue to give 10 times. Second and third years: once a month, 12 times a year.; Drug: Propranolol Hydrochloride; Trial group: BCG + propranolol: after TURBT administered for 2 consecutive years, oral propranolol, starting dose 10mg, tid, then 20mg, tid,lastly increased to 40mg, bid. After the last BCG infusion, propranolol was gradually reduced, in the order of 20 mg, tid to 10 mg, tid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
two-year recurrence-free survival	24 months

Collaborators and Investigators

• Sponsor: Central South University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 6, 2020
• Primary Completion (ANTICIPATED): September 6, 2023
• Study Completion (ANTICIPATED): September 6, 2024

Study Registration Dates

• First Submitted: July 24, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (ACTUAL): July 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2020
• Last Update Submitted That Met QC Criteria: July 29, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: 2020/prop/bladder/CSU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No