Clinical Study to Investigate the Safety and Tolerance of Therapeutic BCG in Postoperative Adjuvant Therapy in Subjects With Moderate to High-risk Non-muscular Invasive Bladder Cancer (NMIBC)

A Phase I Clinical Study to Investigate the Safety and Tolerance of Therapeutic Bacillus Calmette-Guerin( BCG) in Postoperative Adjuvant Therapy in Subjects With Moderate to High-risk Non-muscular Invasive Bladder Cancer (NMIBC)

Phase I clinical study to investigate the safety and tolerance of therapeutic BCG in postoperative adjuvant therapy in subjects with moderate to high-risk non-muscular invasive bladder cancer (NMIBC)

Study Overview

• Status: Completed
• Conditions: Non-muscular Invasive Bladder Cancer
• Intervention / Treatment: Drug: BCG for Therapeutic Use

Detailed Description

The purpose of this study was to evaluate the safety and tolerance, pharmacokinetic characteristics, ablative status, and immune response characteristics of the therapeutic BCG in postoperative adjuvant therapy in subjects with moderate and high-risk non-invasive bladder cancer (NMIBC).

The study consisted of three phases: screening period, administration observation period and safety follow-up period. subjects will be treated with 120 mg BCG.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 415000
      • Hunan Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects were ≥18 years old and ≤85 years old, male or female;
• Subjects with non-myoinvasive bladder uroepithelial carcinoma initially diagnosed by histology [T1, Ta, or Tis stage (carcinoma in situ)] and assessed as moderate to high-risk non-myoinvasive bladder uroepithelial carcinoma requiring BCG injection adjuvant therapy according to the Guidelines for Bladder Cancer Diagnosis and Treatment (2022 edition); (Subjects considered for secondary resection may be included in the study after completion of secondary resection and pathology results confirm moderate or high risk non-myoinvasive bladder cancer);
• ECOG score: 0-2;

• Clinical laboratory tests meet the following characteristics:

  1. Blood routine: no hematopoietic growth factor or transfusion support was used within 14 days prior to enrollment, including: absolute neutrophil value (ANC) ≥1500/mm3 or ≥1.5×109/L; Platelets ≥100000/mm3 or 100×109/L; Hemoglobin ≥9 g/dL.
  2. Liver function: total serum bilirubin ≤1.5× upper limit of normal range (ULN), total serum bilirubin <3×ULN in subjects with Gilbert syndrome, aspartate and alanine aminotransferase (AST and ALT) ≤2.5×ULN.
  3. Renal function: defined as creatinine clearance ≥45 to 50 mL/min as estimated by the Cockcroft Gault formula.
  4. Coagulation function: Activated partial thromboplastin time (APTT) ≤1.5×ULN, International Normalized ratio (INR) ≤1.5×ULN
• The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

• Any of the following:

  1. Patients who are using immunosuppressive drugs, hormone drugs, or radiation therapy that the investigator has determined to be likely to cause systemic BCG disease reactions (patients who hormone injections for thyroid/adrenal resection may be included);
  2. Allergic to BCG vaccine or BCG products;
  3. Have active TB changes or are receiving anti-TB therapy;
  4. Known or suspected intraoperative perforation of the bladder; e Serious gross hematuria before administration was judged by the investigator, and the surgical wound was suspected to have not healed.

  f. The evaluators were judged to be associated with cystitis, or had previously received other bladder perfusion drugs, and were expected to have severe bladder irritation.

  f. Patients with a history of severe adverse reactions to BCG (BCG) sepsis or systemic infection; g. Complete bladder incontinence, defined as the use of six or more pads in a 24-hour period; h. Complete bladder incontinence, defined as the use of six or more pads in a 24-hour period;

• Combined with other genitourinary tumors or malignancies of other organs;
• Accompanied by serious diseases of cardiovascular and cerebrovascular, lung, liver, kidney and other important organs, or severe hypertension or diabetes that researchers judge can not be controlled clinically;
• Patients suffering from acute infectious diseases at the time of screening;
• Evidence of Myoinvasive locally advanced or metastatic urothelial carcinoma, or extrinsic non-Myoinvasive urothelial metastasized cell carcinoma, as determined by the investigator;
• Study participants who had received chemotherapy, radiation therapy, or anti-tumor immunotherapy within 4 weeks prior to treatment (except for immediate postoperative bladder infusion chemotherapy);
• Pregnant or lactating women;
• Subjects who are unable to use effective contraception during the trial period and within 3 months after the last dose;
• Participants who had participated in clinical trials of other therapeutic drugs within 1 month prior to enrollment;
• Known opioid or alcohol dependence;
• Human immunodeficiency virus (HIV) antibody, syphilis specific antibody positive, acute or chronic active hepatitis B (hepatitis B surface antigen (HBsAg) positive, and peripheral blood hepatitis B copy number ≥103/mL), hepatitis C virus (HCV) antibody positive (HCV copy number ≥10/mL);
• Patients with mental disorders or poor compliance as judged by the investigator;
• Any conditions that the investigator believes may increase risk to the subject or interfere with the execution of the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medium/high-risk non-muscle invasive bladder cancer (NMIBC); Medium/high-risk NMIBC (Ta, T1 or Tis) suitable for intravesical BCG treatment.Three phases included: screening period (28 days before the first dose), observation period (6 weeks) and safety follow-up period (7 days after the last dose).	Drug: BCG for Therapeutic Use; Take 120 mg BCG for treatment, dissolved in 40 ~ 50 mL normal saline, bladder perfusion through catheter. The injection was performed once a week for 6 consecutive times.; Other Names: BCG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events(TEAE) and serious Treatment-Emergent Adverse Events;	Probability of AE and SAE after administration.	6 weeks
Effects on clinical laboratory tests index of blood biochemistry, such as the concentration of alanine aminotransferase (ALT).	Probability of abnormal laboratory parameters of blood biochemistry compared with baseline，such as the concentration of alanine aminotransferase (ALT).	6 weeks
Effects on clinical laboratory tests index of blood routine, such as white blood cell count, red blood cell count, platelet count.	Probability of abnormal laboratory parameters of blood routine compared with baseline, such as white blood cell count, red blood cell count, platelet count.	6 weeks
Effects on clinical laboratory tests index of coagulation function, such as activated partial thromboplastin time (APTT).	Probability of abnormal laboratory parameters of coagulation function compared with baseline，such as activated partial thromboplastin time (APTT).	6 weeks
Effects on clinical laboratory tests index of urine routine, such as white urine albumin count, urine red blood cell count.	Probability of abnormal laboratory parameters of urine routine compared with baseline，such as urine albumin count, urine red blood cell count.	6 weeks
Effects on vital signs,such as temperature.	Probability of abnormal laboratory parameters of vital signs compared with baseline，such as temperature(℃).	6 weeks
Effects on P wave, QRS complex, QT interval and so on by 12-lead electrocardiogram.	Probability of abnormal laboratory parameters compared with baseline， including P wave, QRS complex, QT interval and so on by 12-lead electrocardiogram.	6 weeks
Effects on the periodic activity of echocardiography，such as the heart wall recorded as the relationship curve between the corresponding activity and time of each structure.	Probability of abnormal laboratory parameters of echocardiography compared with baseline，such as the heart wall recorded as the relationship curve between the corresponding activity and time of each structure.	6 weeks
Effects on physical examination, refers to the detection and measurement of the development level of human form, structure and function.	Probability of abnormal laboratory parameters of examination compared with baseline，such as any abnormalities in the skin.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exposure condition of the test drug in the blood, refer to plasma concentration of the test drug(BCG).	Exposure to the test drug in the blood，detecting the amount and concentration of drug.	6 weeks
Shedding condition of the test drug in urine.	Exposure to the test drug and in urine，detecting the amount and concentration of drug.	6 weeks
To investigate the immune response characteristics of therapeutic BCG in patients with moderate and high- risk non-invasive bladder cancer after surgery.	The amount and concentration levels of IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF in urine.	6 weeks

Collaborators and Investigators

• Sponsor: Chengdu CoenBiotech Co., Ltd
• Collaborators: Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Actual): February 13, 2023
• Study Completion (Actual): February 13, 2023

Study Registration Dates

• First Submitted: January 28, 2024
• First Submitted That Met QC Criteria: March 29, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: bladder cancer; Non-muscular invasive bladder cancer
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: KN-BCG-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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