Comprehensive Bladder Preservation Therapy on Patients With Muscle Invasive Bladder Cancer

NCT05445648 | Not Yet Recruiting Phase 2

• 1 other identifier: XJTU1AF2022LSK-012
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Nowadays, Immune Checkpoint Inhibitor (ICI) has become one of the new drugs for the treatment of advanced uroepithelial carcinoma. The Food and Drug Administration (FDA) approved ICI for bladder cancer (BC) patients who cannot tolerate cisplatin chemotherapy and whose tumors express programmed cell death protein ligand-1 (PD-L1). However, the efficacy of ICI in bladder preservation therapy for muscular invasive bladder cancer (MIBC) is unknown. With the progressive clinical confirmation of the efficacy of immunotherapy, ICI has moved from second-line to first-line treatment in the indication of advanced unresectable BC. It even has been used in the neoadjuvant and postoperative adjuvant therapy for MIBC and non-muscle invasive bladder cancer (NMIBC) where Bacillus Calmette-Guérin (BCG) therapy has failed. Available studies have shown that neoadjuvant immunotherapy can achieve a pathological complete response (pCR) of 31%-42% for MIBC, regardless of using a single drug or combination, which is higher than that of neoadjuvant chemotherapy, and the incidence of side effects associated with neoadjuvant immunotherapy is lower than that of neoadjuvant chemotherapy, providing an effective treatment option for cisplatin-intolerant patients. Studies have shown that radiotherapy leads to immunogenic cell death, which results in the release and presentation of tumor antigens and directs the recruitment and activation of T cells. It also induces increased expression of PD-L1 in tumor cells, which in turn improves the efficacy of immunotherapy. Thus ICI combined with radiotherapy has a synergistic antitumor effect and does not produce serious toxic side effects similar to those associated with chemotherapeutic agents. This study proposes a novel neoadjuvant immunotherapy-based integrated bladder preservation therapy (neoadjuvant immunotherapy + TURBT + postoperative adjuvant radiotherapy combined with immunotherapy) and investigates the effectiveness and safety of this strategy in bladder preservation treatment strategy.

Conditions

Urinary Bladder Neoplasms

Outcome Measures

Primary Outcomes (2)

• Bladder preservation rate within 1 year, %

  The percentage of enrolled patients who didn't receive radical cystectomy 1 year after neoadjuvant immunotherapy (Tislelizumab Injection) started

  1 year after neoadjuvant immunotherapy (Tislelizumab Injection) started

• Pathological complete response rate after neoadjuvant immunotherapy, %

  the percentage of enrolled patients who demonstrated pathological complete response after neoadjuvant immunotherapy, confirmed by pathological results of specimen extracted from TURBT.

  right after TURBT and pathological examination of surgical specimen has concluded.

Secondary Outcomes (2)

• Overall survival time, day

  from the start of neoadjuvant immunotherapy to 1) death of the patients by any cause; 2) the end of followup if patients are still alive by that time; 3) last follow up date if patients are lost, whichever comes first, assessed up to 156 weeks

• Adverse event

  from the start of neoadjuvant immunotherapy to the last followup check, assessed up to 156 weeks

Study Arms (1)

patients treated with immunotherapy-based bladder preservation therapy

EXPERIMENTAL

Neoadjuvant immunotherapy + TURBT + postoperative adjuvant radiotherapy combined with immunotherapy.

Drug: Tislelizumab Injection; Procedure: Transurethral resection of bladder tumor; Radiation: Adjuvant radiotherapy

Interventions

Tislelizumab Injection DRUG

After patient recruitment, every patient first receives a regimen of tislelizumab injection 200 mg every time , q3w, 4 times in total. Then all patients, if operable, undergo TURBT. The first day after TURBT, patients again start to receives a regimen of tislelizumab Injection 200 mg every time , q3w, 4 times in total. Meanwhile, on the eighth day after TURBT, patients start to receive radiotherapy. The total radiation dosage is 50.4 Gy (patients receive radiotherapy 28 times, dosage being 1.8 Gy every time), with the total radiation dosage on pelvis area being 45 Gy and total radiation dosage on bladder area being 50.4 Gy.

Also known as: BGB-A317, BeiGene

patients treated with immunotherapy-based bladder preservation therapy

Transurethral resection of bladder tumor PROCEDURE

After the initial tislelizumab injection regimen, patients undergo clinical assessment and receive transurethral resection of bladder tumor if operable.

patients treated with immunotherapy-based bladder preservation therapy

Adjuvant radiotherapy RADIATION

On the eighth day after TURBT, patients start to receive radiotherapy. The total radiation dosage is 50.4 Gy (patients receive radiotherapy 28 times, dosage being 1.8 Gy every time), with the total radiation dosage on pelvis area being 45 Gy and total radiation dosage on bladder area being 50.4 Gy.

patients treated with immunotherapy-based bladder preservation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Voluntary participation in this trial, able to provide a written version of informed consent, and able to understand and agree to comply with the requirements of this study.
• BC patients with cT2-T4aN0M0 tumor/ lymph node/ metastasis (TNM) (AJCC 8th edition) staging based on histopathological confirmation by biopsy specimen and CT/MRI assessment.
• ECOG performance status grade less than or equal to 1

You may not qualify if:

• Cancer in situ (CIS) confirmed by biopsy pathology.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4(CTLA)-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways (excluding BCG treatment).
• Received other approved systemic anticancer therapy or systemic immunomodulators within 28 days prior to enrollment.
• Severe chronic or active infection requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to enrollment
• Received herbal or proprietary Chinese medicine for cancer inhibition within 14 days prior to admission.
• Received live vaccination within 28 days prior to admission.
• Has need for long-term heavy use of hormones or other immunosuppressive drugs.
• Potassium, sodium, or calcium abnormalities affecting treatment, interstitial lung disease, non-infectious pneumonia, or other uncontrolled systemic diseases, including diabetes, hypertension, or active heart disease.
• Patients with chronic hepatitis B, hepatitis B virus carriers, or active hepatitis C.
• Active, known or suspected autoimmune disease requiring systemic therapy.
• Patients with end-stage renal disease (GFR \<15 mL/min) or requiring dialysis.
• Other active neoplastic disease.
• Uncontrolled severe physical or mental illness.
• Pregnant or lactating women.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead
• BeiGene: collaborator

Study Sites (1)

First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

tislelizumab; Transurethral Resection of Bladder; Radiotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative; Combined Modality Therapy; Therapeutics; Radiotherapy

Study Officials

• Jinhai Fan, MD

  First affiliated hospital of Xian jiaotong university

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinhai Fan, MD

CONTACT

0086-13259906969; fanjinhai@aliyun.com

Yaodong Zhang, BM

CONTACT

0086-18829552006; nickvzhang@foxmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2022
• First Posted: July 6, 2022
• Study Start: February 1, 2023
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2026
• Last Updated: December 28, 2022

Record last verified: 2022-06

Locations

CN (1)