Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Antibodies

Antibodies, Monoclonal

Tislelizumab

Cisplatin

Immunomodulating Agents

Immunoglobulins

Antimetabolites

Antineoplastic Agents, Immunological

Patients will receive 4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before cystectomy discussion. The patients reach clinical complete remission will receive tislelizumab maintenance therapy for a year or 13 cycles.

70mg/m2 IV on Day 1 of 3-week, for 4 cycles. Dose fractionation is permissible.

1000mg/m2, Day 1 and Day 8 of 3-week, for 4 cycles

Danfeng Xu

Wenhao Lin

Lu Chen

Yi Gao

Fang Huang

Guangliang Jiang

This study is designed prospectively to investigate the safety, efficacy and feasibility of cisplatin-based chemotherapy combined with tislelizumab as bladder sparing treatment for patients with muscle invasive bladder cancer (MIBC) which are eligible for cisplatin. The patients that achieved clinical remission after 4 cycles of cisplatin/gemcitabine and tislelizumab, will receive tislelizumab maintenance therapy for a year or 13 cycles. Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The safety, tolerability, and efficacy of tislelizumab in patients with PD-L1 positive urothelial carcinoma who progressed during/following platinum-containing therapy was proved in a phase 2 trial (CTR20170071).

This trial investigates the efficacy of cisplatin-based chemotherapy combined with Tislelizumab to induce clinical complete remission of muscle invasive bladder cancer and the feasibility to provide bladder sparing treatment for these patients.

The patients that meet the Inclusion and Exclusion Criteria will treat with 4 cycles of cisplatin-based chemotherapy combined with Tislelizumab (200mg per cycle) prior to cystectomy discussion. The patients that show clinical benefit will receive tislelizumab for bladder sparing. Forty patients will be enrolled in this trial.

Cisplatin-based chemotherapy combined with tislelizumab

Chemotherapy Combined With Tislelizumab as Bladder Sparing Option for Patients With Muscle Invasive Bladder Cancer

A Prospective, Single Center Clinical Study to Examine Cisplatin-based Chemotherapy Combined With Tislelizumab as Bladder Sparing Treatment for Patients With Muscle Invasive Bladder Cancer

The clinical complete remission rate (cCR) was defined as the proportion of patients with clinically confirmed cT0 or cTa(AJCC Cancer Staging Manual,8th ed. 2017 edition ).The cT0 or cTa was assessed by cystoscopy examination at 12 weeks after the initiation of combination therapy. Two-sided Clopper-Pearson 95% confidence intervals were constructed to evaluate the accuracy of cCR.

Duration of cCR was defined as the delay between date of reaching cCR and tumour relapse or progression.The status of cCR was evaluated by cystoscopy examination every 3 months after the combination therapy. Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

Bladder-intact event-free survival (BI-EFS) was defined as the time from initiation of combination therapy to the date of occurrence of any following event ：

1. Recurrence of muscle-invasive bladder cancer based on follow-up cystoscopic evaluation
2. Lymph node metastases based on CT/MR/PET-CT
3. Distant metastases based on CT/MR/PET-CT
4. Bladder cancer-related death
5. Cystectomy due to any reason

BI-EFS will be estimated with Kaplan-Meier estimators and corresponding 95% confidence intervals.

Ruijin Hospital

Anti-Infective Agents

Nivolumab

Capecitabine

Ipilimumab

Mitomycins

Mitomycin

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Nivolumab monotherapy at 480mg fixed dose administered intravenously (IV) over 60 minutes every 4 weeks for 3 doses.

All study participants can opt for an additional 10 administrations of nivolumab 480mg fixed dose at intervals of 4 weeks, from week 13 to week 52.

Nivolumab at 3 mg/kg administered IV over 60 minutes combined with ipilimumab at 1 mg/kg administered IV over 90 minutes every 3 weeks for 4 doses.

All study participants can opt for an additional 10 administrations of nivolumab 480mg fixed dose at intervals of 4 weeks, from week 13 to week 52.

Nivolumab at 1 mg/kg administered IV over 60 minutes combined with ipilimumab at 3 mg/kg administered IV over 90 minutes every 3 weeks for 4 doses.

All study participants can opt for an additional 10 administrations of nivolumab 480mg fixed dose at intervals of 4 weeks, from week 13 to week 52.

nivolumab 480mg

nivolumab 3mg/kg, ipilimumab 1mg/kg

nivolumab 1mg/kg, ipilimumab 3mg/kg

Adriaan D. Bins, MD PhD

Tom van der Hulle, MD, PhD

A multicenter Phase 1b/2, two stage, open label study of MMC/Capecitabine ChRT combined with nivolumab monotherapy or nivolumab and ipilimumab combination therapy in adult (\>18 years) subjects with non-metastatic muscle invasive bladder cancer that qualify for ChRT with curative intent.

Immunotherapy combined with chemoradiation for localized bladder cancer may exhibit improved efficacy with an acceptable toxicity profile.

The aim of this phase 1b/2, two stage, open label study of MMC/Capecitabine ChRT combined with nivolumab monotherapy or nivolumab and ipilimumab combination therapy stuy is: to assess the feasibility and safety, the disease free survival (DFS) and disease free survival rate (DFS-rate) of the addition of nivolumab and/or ipilimumab to MMC/capecitabine chemoradiation of the bladder.

Patients will be treated with radiation therapy over 4 weeks and receive MMC IV on day1 of radiation therapy and capecitabine on each day of radiation therapy as radiosensitizers.

Phase-1b: enrollment of maximum of 30 patients with a maximum of 10 patients per treatment regimen, in order to determine optimal regimen based on the occurrence of dose limiting toxicities (DLT).

* Regimen-A: immunotherapy (w1-12) consists of nivolumab 480mg (fixed dose), on day(d)1, d29 and d57.
* Regimen-B: immunotherapy (w1-12) consists of ipilimumab 1 mg/kg together with Nivolumab 3mg/kg on d1, d22, d43 and d65.
* Regimen-C: immunotherapy (w1-12) consists of ipilimumab 3 mg/kg and nivolumab 1 mg/kg on d1, d22, d43 and d65.

All study participants can opt for an additional 10 administrations of nivolumab 480mg fixed dose at intervals of 4 weeks, from week 13 to week 52.

Phase-2: enrollment of an additional 20 subjects at the regimen determined to be optimal in the phase-1b part.

A Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study

A Phase 1b-2 Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study

Cystoscopy at week 12 and week 24 will be performed. From week 12 onward 3-montly CT scans will be done in the context of the current standard of care up to 5 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Chemotherapy Combined With Tislelizumab as Bladder Sparing Option for Patients With Muscle Invasive Bladder Cancer	NCT04909775	Muscle-Invasive...	Tislelizumab Cisplatin Gemcitabine	18 Years - 75 Years	Ruijin Hospital
A Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study	NCT03844256	Urinary Bladder... Invasive Bladde...	nivolumab 480mg nivolumab 3mg/k... nivolumab 1mg/k...	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Spots Global Cancer Trial Database for bladder sparing treatment