AzTrials
AzTrials

Bladder Urothelial CarcinomaPhase 1NCT07353294

Propranolol With Tislelizumab Plus GC in Neoadjuvant Bladder UC

A Phase 1 study testing propranolol, Tislelizumab and gemcitabine in people with Bladder Urothelial Carcinoma and Lymph Node Metastasis, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial summary

This is a prospective, multicenter, Phase Ib clinical study designed to evaluate the safety and preliminary efficacy of propranolol combined with tislelizumab plus gemcitabine/cisplatin (GC) as neoadjuvant therapy for patients with bladder urothelial carcinoma with clinical lymph node involvement (cT1-T4aN1-3M0). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
propranolol, Tislelizumab and gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteChina
Study dates
1 Jan 2026to 30 Jun 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Voluntarily agrees to participate in the study, is able to provide written informed consent, and is willing to comply with study procedures and visit schedules.
  • Age ≥ 18 years at the time of consent; sex unrestricted.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Histologically confirmed bladder urothelial carcinoma with clinical lymph node involvement (cT1-T4a, N1-N3, M0) based on the AJCC 8th edition. Mixed histology is permitted if the urothelial carcinoma component is ≥ 50%.
  • No antihypertensive medication used during screening, with resting systolic blood pressure between 110-140 mmHg measured under natural conditions.
  • Adequate organ function as demonstrated by laboratory results obtained within 14 days prior to enrollment:
Show all 15Show fewer
  • No administration of hematopoietic growth factors within 14 days prior to sample collection.
  • Absolute neutrophil count ≥ 1.5 × 10⁹/L ii. Platelet count ≥ 90 × 10⁹/L iii. Hemoglobin ≥ 90 g/L b. INR or aPTT ≤ 1.5 × ULN c. Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN in patients with Gilbert syndrome or indirect hyperbilirubinemia) d. AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN e. Preoperative pulmonary function assessment indicating tolerance of major abdominal surgery.
  • Cisplatin-eligible patients, or cisplatin-ineligible patients who meet at least one of the following:
  • ECOG performance status > 1 or Karnofsky 60-70%
  • Creatinine clearance < 60 mL/min
  • Grade ≥ 2 hearing loss (NCI-CTCAE v5.0)
  • Grade ≥ 2 peripheral neuropathy (NCI-CTCAE v5.0)
  • New York Heart Association (NYHA) class III or above heart failure
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and agree to use effective contraception during the study and for ≥ 120 days after the last dose. Male participants must agree to use effective contraception during the study and for ≥ 120 days after the last dose.

Who cannot join

  • Prior treatment with PD-1, PD-L1, PD-L2, CTLA-4 inhibitors, or other T-cell co-stimulatory/checkpoint agents.
  • Systemic antineoplastic therapy or immunomodulatory therapy within 28 days prior to enrollment, including interferon, interleukin-2, or TNF-based agents.
  • Prior radiotherapy for bladder cancer.
  • Prior systemic anticancer therapy except:
  • Previous systemic chemotherapy completed ≥ 12 months before initiation of study treatment.
  • Intravesical chemotherapy or immunotherapy completed ≥ 7 days prior to initiation of study treatment.
Show all 27Show fewer
  • Major surgery or significant trauma within 28 days prior to enrollment (vascular access placement and TURBT excluded).
  • Receipt of live attenuated vaccines within 28 days prior to enrollment. Inactivated influenza vaccination is allowed; intranasal influenza vaccine is not permitted.
  • Active autoimmune disease requiring systemic therapy, as judged by the investigator.
  • Long-term systemic corticosteroid therapy or other immunosuppressive medications judged to interfere with study treatment.
  • Uncontrolled systemic disease that may interfere with treatment, including:
  • Clinically relevant electrolyte abnormalities
  • Hypoalbuminemia
  • Interstitial lung disease or non-infectious pneumonitis
  • Uncontrolled diabetes, hypertension, or cardiovascular disease (including unstable angina, myocardial infarction, symptomatic heart failure, or medically managed ventricular arrhythmias within 6 months).
  • Chronic hepatitis B infection with HBV DNA ≥ 500 IU/mL (2,500 copies/mL). Patients with inactive HBsAg carrier status or viral suppression (HBV DNA < 500 IU/mL) after antiviral therapy may be enrolled. HBV DNA testing is required if anti-HBc is positive.
  • Active hepatitis C infection. Patients who are HCV antibody negative, or HCV antibody positive but HCV RNA negative, are eligible.
  • History of immunodeficiency disorders (including HIV infection), congenital or acquired immune deficiency, or prior allogeneic stem cell transplantation or organ transplantation.
  • Known hypersensitivity to monoclonal antibodies, or known allergy to propranolol or other β-adrenergic receptor blockers.
  • Toxicities from previous therapies have not returned to baseline or stabilized, unless deemed not to pose a safety risk by the investigator (e.g., alopecia, neuropathy, specific laboratory abnormalities).
  • Contraindications to propranolol, including but not limited to:
  • Unstable angina
  • Decompensated heart failure
  • Symptomatic sinus bradycardia
  • Atrioventricular block
  • Severe asthma or bronchospasm
  • Current use of oral or intravenous β-blockers (e.g., atenolol, bisoprolol, carvedilol, metoprolol) that cannot be safely discontinued or transitioned. If previously used, a washout period of at least 14 days with medical reassessment is required before enrollment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site

  • Sun Yat-sen Memorial Hospital, Sun Yat-sen University

    Guangzhou, Guangdong, 510000

Other trials in China

About this study

Official title: A Phase Ib Prospective Clinical Study Evaluating the Safety and Efficacy of Propranolol Combined With Tislelizumab Plus Gemcitabine/Cisplatin as Neoadjuvant Therapy for cT1-4aN1-3M0 Bladder Urothelial Carcinoma

This is a prospective, multicenter, Phase Ib clinical study designed to evaluate the safety and preliminary efficacy of propranolol combined with tislelizumab plus gemcitabine/cisplatin (GC) as neoadjuvant therapy for patients with bladder urothelial carcinoma with clinical lymph node involvement (cT1-T4aN1-3M0). Current neoadjuvant immunochemotherapy regimens can improve clinical outcomes in cisplatin-eligible patients; however, patients with lymph node metastasis show a significantly poorer pathological complete response (pCR) rate compared with non-metastatic cases. Real-world clinical observations have shown that more than 20% of patients achieve complete response in the primary tumor after immunotherapy but have persistent or progressive positive lymph nodes, suggesting unique resistance mechanisms within lymph node metastatic lesions.

Preclinical studies conducted by our team demonstrated that sympathetic innervation within lymph nodes releases norepinephrine, which activates β-adrenergic signaling in metastatic tumor cells and promotes lipid metabolic reprogramming, leading to CD8⁺ T-cell exhaustion and immune resistance. Propranolol, a non-selective β-adrenergic blocker, may reduce metabolic stress and restore antitumor immunity, potentially enhancing the efficacy of immune checkpoint blockade.

Read more

In this study, enrolled patients will receive oral propranolol in combination with intravenous tislelizumab and standard GC chemotherapy prior to surgery. Participants will be closely monitored for treatment-related adverse events, including cardiovascular events, hematologic toxicity, and immune-related reactions. The primary endpoint is dose-limiting toxicity (DLT). Secondary endpoints include pathological complete response (pCR), pathological downstaging, safety, and survival outcomes. Exploratory analyses will evaluate changes in immune cell populations in tumor tissues, lymph nodes, and peripheral blood.

The results of this study aim to provide evidence for new neoadjuvant strategies targeting lymph node metastatic bladder cancer and support the development of personalized therapeutic approaches.

Being tested
propranolol, Tislelizumab, gemcitabine, Cisplatin
Keywords
Bladder urothelial carcinoma, Lymph Node Metastasis, Neoadjuvant therapy, Tislelizumab, Gemcitabine, Cisplatin, Propranolol
Medical subject headings
Lymphatic Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • propranololDrug

    Also called β-blocker, Propranolol Hydrochloride

    Propranolol will be administered orally as a non-selective β-adrenergic receptor blocker. Treatment will start at a low dose and may be escalated to a maximum of 40 mg twice daily if tolerated. Vital signs will be monitored regularly, and dose adjustment, interruption, or discontinuation may occur based on predefined cardiovascular safety criteria.

  • TislelizumabDrug

    Tislelizumab will be administered intravenously as an anti-PD-1 monoclonal antibody according to standard dosing schedules for neoadjuvant immunotherapy. Infusion monitoring will be conducted in a facility equipped for emergency management. Dose interruption or discontinuation may occur if immune-related adverse events develop.

  • gemcitabineDrug

    Gemcitabine will be administered intravenously as part of the gemcitabine/cisplatin chemotherapy regimen during neoadjuvant treatment. Hematologic parameters and organ function will be regularly monitored, and chemotherapy dose may be modified based on toxicity and tolerability according to institutional standards.

  • CisplatinDrug

    Cisplatin will be administered intravenously as part of the gemcitabine/cisplatin regimen. Renal function, electrolyte balance, and hematologic tests will be routinely monitored. Dosing may be adjusted or withheld according to predefined safety criteria and institutional guidelines for cisplatin-based chemotherapy.

Study groups in NCT07353294
Study groupRoleWhat they receive
Propranolol + Tislelizumab + Gemcitabine/CisplatinExperimentalPatients will receive oral propranolol in combination with intravenous tislelizumab and gemcitabine/cisplatin as neoadjuvant therapy prior to radical surgery. Propranolol will be administered in escalating doses up to a maximum of 40 mg twice daily if tolerated. Tislelizumab is given intravenously every treatment cycle. Gemcitabine and cisplatin will be administered according to standard GC chemotherapy dosing. Participants will be monitored for treatment-related adverse events, including cardiovascular, hematologic, and immune-related toxicities. Dose adjustments, treatment interruptions, or discontinuation may be implemented according to predefined safety criteria.
Receives: Drug: propranolol; Drug: Tislelizumab; Drug: gemcitabine; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Dose-Limiting Toxicities (DLTs)

    Dose-limiting toxicities (DLTs) are defined as treatment-related adverse events occurring during the first treatment cycle that meet predefined severity criteria based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. DLTs may include grade 3 or higher non-hematologic toxicity, grade 4 hematologic toxicity, or clinically significant events leading to treatment interruption or discontinuation, as determined by the investigators.

    Measured: At the end of Cycle 1 (each cycle is 28 days)

Secondary outcomes (5)

  1. Pathological Complete Response (pCR) Rate

    Pathological complete response (pCR) is defined as the absence of any residual tumor in the primary bladder lesion and in all examined regional lymph nodes following neoadjuvant therapy and surgical resection (pT0N0). The proportion of participants achieving pCR will be calculated relative to the total number of evaluable participants.

    Measured: At the time of surgery

  2. Pathological Downstaging Rate

    Pathological downstaging is defined as a postoperative pathological tumor stage (ypT) lower than the baseline clinical stage (cT), with downstaging to ypT2 or lower considered as treatment-induced downstaging. The proportion of evaluable participants achieving pathological downstaging will be recorded.

    Measured: At the time of surgery

  3. Incidence of Treatment-Related Adverse Events

    Adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) will be collected and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Events will be summarized by frequency, severity grade, and relationship to study treatment.

    Measured: From first dose through 30 days after the last administration of study treatment

  4. Progression-Free Survival (PFS)

    PFS is defined as the time from study enrollment to the first documented disease progression, local or distant recurrence, or death from any cause, whichever occurs first. Participants without an event will be censored at the date of last disease assessment.

    Measured: Up to 24 months after surgery

  5. Overall Survival (OS)

    OS is defined as the time from study enrollment to death from any cause. Participants who remain alive at the end of follow-up will be censored at the date of last known contact.

    Measured: Up to 36 months after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2026
  2. Study start1 Jan 2026
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion30 Jun 2029 (estimated)

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single-arm, open-label interventional study evaluating the combination of propranolol, tislelizumab and GC.
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07353294
Sponsor's protocol ID
SYSKY-2025-837-02
Status last verified
Apr 2026
First submitted
11 Dec 2025
Last updated
22 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing propranolol, Tislelizumab and gemcitabine in people with Bladder Urothelial Carcinoma and Lymph Node Metastasis, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University 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 15 inclusion and 27 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: enrolling by invitation, as of the sponsor's last update on 22 Apr 2026. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose-Limiting Toxicities (DLTs) (time frame: At the end of Cycle 1 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07353294.

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 22 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in