Non-muscle-invasive Bladder CancerPhase 4NCT05580354
Safety and Efficacy of BCG Combined With Tislelizumab for BCG-untreated Patients With High-risk Non-muscle Invasive Bladder Cancer
A Phase 4 study testing BCG combined with Tislelizumab in people with Non-muscle-invasive Bladder Cancer, run by Ruijin Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-muscle-invasive Bladder Cancer
- What is being tested?
- BCG combined with Tislelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteChina
- Study dates
- 9 Oct 2022to 31 May 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality
Danfeng Xu, 02164370045, xdf12036@rjh.com.cn
Zhiyang Ma, +8618917359966, zy_ma2017@163.com
About this study
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
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.
Read the 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.
- Conditions
- Non-muscle-invasive Bladder Cancer
- Being tested
- BCG combined with Tislelizumab
- Keywords
- Non-muscle-invasive Bladder Cancer, Tislelizumab, BCG
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG combined with TislelizumabDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 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). Receives: Drug: BCG combined with Tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relapse-Free Survival （RFS）
Relapse-Free Survival （RFS） is defined as the time from enrollment to any event of recurrence or death.
Measured: 12 month
Secondary outcomes (5)
Overall survival (OS)
Overall survival (OS) is defined as the time from enrollment to death from any cause.
Measured: 12 month
Cystectomy-free survival
Cystectomy-free survival is defined as the time from enrollment to radical cystectomy.
Measured: 12 month
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.
Measured: 12 month
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.
Measured: 12 month
Correlation between biological markers and tumor molecular subtypes and efficacy.
Correlation between biological markers and tumor molecular subtypes and efficacy.
Measured: 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2022
- Study start9 Oct 2022 (estimated)
- Primary completion9 Oct 2024 (estimated)
- Study completion31 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-muscle-invasive Bladder CancerStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- BCG combined with Tislelizumab
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05580354
- Sponsor's protocol ID
- SPARE-007
- Status last verified
- Oct 2022
- First submitted
- 12 Oct 2022
- Last updated
- 14 Oct 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05580354
- Acronym / sponsor ID
- SPARE-007
- Conditions
- Non-muscle-invasive Bladder Cancer
- Keywords
- Non-muscle-invasive Bladder Cancer, Tislelizumab, BCG
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 9 Oct 2022 (estimated)
- Primary completion
- 9 Oct 2024 (estimated)
- Study completion
- 31 May 2025 (estimated)
- First posted
- 14 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- BCG combined with Tislelizumab
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: BCG combined with TislelizumabPatients 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- ≥ 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)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG combined with TislelizumabPatients 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). | Drug | Arm 1 |
Primary outcome
Relapse-Free Survival （RFS）
Time frame: 12 month
Relapse-Free Survival （RFS） is defined as the time from enrollment to any event of recurrence or death.
5 secondary outcomes
Overall survival (OS)
Time frame: 12 month
Cystectomy-free survival
Time frame: 12 month
Duration of Response (DOR)
Time frame: 12 month
Progression free survival to muscle-invasive or metastatic disease or death.
Time frame: 12 month
Correlation between biological markers and tumor molecular subtypes and efficacy.
Time frame: 12 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing BCG combined with Tislelizumab in people with Non-muscle-invasive Bladder Cancer, run by Ruijin Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Danfeng Xu ((021)64370045 ext. 666062, xdf12036@rjh.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relapse-Free Survival （RFS） (time frame: 12 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2022.