Back to results

Safety and Efficacy of BCG Combined With Tislelizumab for BCG-untreated Patients With High-risk Non-muscle Invasive Bladder Cancer

Primary Purpose

Non-muscle-invasive Bladder Cancer

Status

Not yet recruiting

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

BCG combined with Tislelizumab

About this trial

This is an interventional treatment trial for Non-muscle-invasive Bladder Cancer focused on measuring Non-muscle-invasive Bladder Cancer, Tislelizumab, BCG

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥ 18 and ≤75 years old on day of signing informed consent
Signing informed consent
Patients with histologically confirmed high-risk NMIBC after TURBT (Patients with mixed histology, predominantly transitional cells, could be enrolled.) High grade pathology (any of the following conditions)
- CIS
- T1
- >3cm
- Multifocal
Patients must be willing to provide a blood sample and a TURBT specimen must be taken at baseline.
For patients with T1 or suspected incomplete tumor resection after first TURBT, incomplete initial resection or no muscle in original specimen, they should undergo TURBT again within 2-6 weeks.
No distant metastasis confirmed by CT or MRI in the chest, abdomen, or pelvic cavity within 42 days before treatment.
ECOG performance status of ≤2
Life expectancy ≥12 weeks
Well-controlled blood pressure and within 7 days before treatment <160/95mmHg
Normal organ function within 7 days before treatment
- HB≥90 g/L
- ANC≥1.5×109 /L
- PLT≥100×109 /L
- T-BIL≤1.5×ULN
- ALT, AST≤2.5×ULN
- eGFR≥ 20ml/min
- INR, APTT≤1.5× ULN.

Exclusion Criteria:

Received prior therapies targeting PD-1 or PD-L1.
Received prior intravesical therapy of BCG.
Receive any approved anticancer therapy, including systemic and intravesical chemotherapy within 21 days before enrollment.
Receive any other trial drug or participate in another therapeutic clinical study within 28 days before enrollment.
History of severe hypersensitivity reactions to other monoclonal antibodies.
History of other malignancy.
Active tuberculosis.
Severe infections occur within 4 weeks prior to enrollment, including but not limited to infectious complications leading to hospitalization, bacteremia, or severe pneumonia.
A known history of HIV infection.
Untreated chronic hepatitis B patients or hepatitis B virus carriers whose HBV DNA≥500 IU/mL
Patients with active hepatitis C
Participants with active autoimmune diseases or history of autoimmune diseases that may relapse
Clinically significant cardiovascular disease, including heart disease (NYHA ≥Ⅲ), myocardial infarction, unstable arrhythmia or unstable angina within 3 months before enrollment.
A known history of LVEF<40%
Prior allogeneic stem cell transplantation or organ transplantation
History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases.
Underlying diseases that the investigator believes are not conducive to study treatment or difficult to explain by drug toxicity or adverse events.
Receive hormone therapy or other immunosuppressive therapy within 14 days before enrollment.

Sites / Locations

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

Patients will receive 17 cycles of Tislelizumab (200mg per cycle) in combination with BCG (6-week induction course of 120mg followed by maintenance with 3 weekly infusions of 120mg at months 3,6,12).

Outcomes

Primary Outcome Measures

Relapse-Free Survival （RFS）

Relapse-Free Survival （RFS） is defined as the time from enrollment to any event of recurrence or death.

Secondary Outcome Measures

Overall survival (OS)

Overall survival (OS) is defined as the time from enrollment to death from any cause.

Cystectomy-free survival

Cystectomy-free survival is defined as the time from enrollment to radical cystectomy.

Duration of Response (DOR)

Duration of Response (DOR) is defined as the time from CR to any event of recurrence, progression, or death of high-risk NMIBC.

Progression free survival to muscle-invasive or metastatic disease or death.

Progression free survival to muscle-invasive or metastatic disease or death is defined as the time from CR to any event of tumor myometrium invasion, metastasis, or death.

Correlation between biological markers and tumor molecular subtypes and efficacy.

Full Information

NCT ID

NCT05580354

First Posted

October 12, 2022

Last Updated

October 12, 2022

Sponsor

Ruijin Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05580354

Brief Title

Safety and Efficacy of BCG Combined With Tislelizumab for BCG-untreated Patients With High-risk Non-muscle Invasive Bladder Cancer

Official Title

A Prospective, Single Center Clinical Study to Examine the Safety and Efficacy of BCG Combined With Tislelizumab as Treatment for BCG-untreated Patients With High-grade Non-muscle-invasive Bladder Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 9, 2022 (Anticipated)

Primary Completion Date

October 9, 2024 (Anticipated)

Study Completion Date

May 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ruijin Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

For patients with high-risk non-muscle-invasive bladder cancer (NMIBC), intravesical therapy of BCG is the standard treatment proved to reduce the risk of recurrence and progression. However, there are patients failed to complete the whole treatment due to the long period and some patients showed no response to BCG or suffered tumor progression after BCG treatment. The aim of this study is to examine the efficacy and safety of intravesical therapy of BCG combined with PD-1 monoclonal antibody as the treatment of high-risk NMIBC patients without BCG treatment. At the same time, transcriptome sequencing is used to analyze the correlation between the efficacy of the treatment and the level of immune cell infiltration and tumor molecular subtypes.

Detailed Description

Bladder cancer is a common malignant tumor, with non-muscle-invasive bladder cancer (NMIBC) accounting for approximately 75% of bladder cancer patients. Of these NMIBC patients, 50-70% have tumor recurrence and 15% have tumor progression, thus most patients may require prolonged cystoscopy and therapeutic intervention. According to the EAU guideline, intravesical therapy of BCG is the standard treatment of high-risk NMIBC patients, as it reduces the risk of tumor recurrence and progression. There has long been controversial about the dosage and period of BCG treatment and long-term BCG treatment may cause frequent adverse effects such as hematuria and urinary frequency，because of which many patients failed to complete the whole period of treatment. Also, some patients showed no response to BCG and underwent tumor progression after BCG treatment. Based on the above considerations, trying to improve the treatment for NMBIC patients is important. Recent study showed that the rate of BCG response and tumor recurrence after BCG treatment may be related to PD-L1 expression, indicating that the therapeutic effect of BCG treatment combined with ICIs remains to be explored. Besides, since the molecular subtype of NMIBC has not been well standardized, and molecular subtype may guide treatment options, the correlation between NMIBC molecular subtypes and immunotherapy still remains to be verified by further studies. Since circulating tumour DNA (ctDNA) holding promise as a biomarker for molecular residual disease and relapse, next generation sequencing (NGS) of ctDNA may also benefit treatment options. This trial investigates the safety and efficacy of intravesical therapy of BCG combined with Tislelizumab for BCG-untreated patients with high-risk NMIBC as well as the relationship between the efficacy and tumor subtypes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-muscle-invasive Bladder Cancer

Keywords

Non-muscle-invasive Bladder Cancer, Tislelizumab, BCG

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Model Description

BCG combined with Tislelizumab

Masking

None (Open Label)

Allocation

N/A

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Description

Patients will receive 17 cycles of Tislelizumab (200mg per cycle) in combination with BCG (6-week induction course of 120mg followed by maintenance with 3 weekly infusions of 120mg at months 3,6,12).

Intervention Type

Drug

Intervention Name(s)

BCG combined with Tislelizumab

Intervention Description

Patients will receive 17 cycles of Tislelizumab (200mg per cycle) in combination with BCG (6-week induction course of 120mg followed by maintenance with 3 weekly infusions of 120mg at months 3,6,12).

Primary Outcome Measure Information:

Title

Relapse-Free Survival （RFS）

Description

Relapse-Free Survival （RFS） is defined as the time from enrollment to any event of recurrence or death.

Time Frame

12 month

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

Overall survival (OS) is defined as the time from enrollment to death from any cause.

Time Frame

12 month

Title

Cystectomy-free survival

Description

Cystectomy-free survival is defined as the time from enrollment to radical cystectomy.

Time Frame

12 month

Title

Duration of Response (DOR)

Description

Duration of Response (DOR) is defined as the time from CR to any event of recurrence, progression, or death of high-risk NMIBC.

Time Frame

12 month

Title

Progression free survival to muscle-invasive or metastatic disease or death.

Description

Progression free survival to muscle-invasive or metastatic disease or death is defined as the time from CR to any event of tumor myometrium invasion, metastasis, or death.

Time Frame

12 month

Title

Correlation between biological markers and tumor molecular subtypes and efficacy.

Description

Correlation between biological markers and tumor molecular subtypes and efficacy.

Time Frame

12 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ≥ 18 and ≤75 years old on day of signing informed consent Signing informed consent Patients with histologically confirmed high-risk NMIBC after TURBT (Patients with mixed histology, predominantly transitional cells, could be enrolled.) High grade pathology (any of the following conditions) CIS T1 >3cm Multifocal Patients must be willing to provide a blood sample and a TURBT specimen must be taken at baseline. For patients with T1 or suspected incomplete tumor resection after first TURBT, incomplete initial resection or no muscle in original specimen, they should undergo TURBT again within 2-6 weeks. No distant metastasis confirmed by CT or MRI in the chest, abdomen, or pelvic cavity within 42 days before treatment. ECOG performance status of ≤2 Life expectancy ≥12 weeks Well-controlled blood pressure and within 7 days before treatment <160/95mmHg Normal organ function within 7 days before treatment HB≥90 g/L ANC≥1.5×109 /L PLT≥100×109 /L T-BIL≤1.5×ULN ALT, AST≤2.5×ULN eGFR≥ 20ml/min INR, APTT≤1.5× ULN. Exclusion Criteria: Received prior therapies targeting PD-1 or PD-L1. Received prior intravesical therapy of BCG. Receive any approved anticancer therapy, including systemic and intravesical chemotherapy within 21 days before enrollment. Receive any other trial drug or participate in another therapeutic clinical study within 28 days before enrollment. History of severe hypersensitivity reactions to other monoclonal antibodies. History of other malignancy. Active tuberculosis. Severe infections occur within 4 weeks prior to enrollment, including but not limited to infectious complications leading to hospitalization, bacteremia, or severe pneumonia. A known history of HIV infection. Untreated chronic hepatitis B patients or hepatitis B virus carriers whose HBV DNA≥500 IU/mL Patients with active hepatitis C Participants with active autoimmune diseases or history of autoimmune diseases that may relapse Clinically significant cardiovascular disease, including heart disease (NYHA ≥Ⅲ), myocardial infarction, unstable arrhythmia or unstable angina within 3 months before enrollment. A known history of LVEF<40% Prior allogeneic stem cell transplantation or organ transplantation History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases. Underlying diseases that the investigator believes are not conducive to study treatment or difficult to explain by drug toxicity or adverse events. Receive hormone therapy or other immunosuppressive therapy within 14 days before enrollment.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Danfeng Xu

Phone

(021)64370045

Ext

666062

xdf12036@rjh.com.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Zhiyang Ma

Phone

+8618917359966

zy_ma2017@163.com

Facility Information:

Facility Name

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

City

Shanghai

State/Province

Shanghai

Country

China

Facility Contact: