Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

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

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Fluorouracil

Capecitabine

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Induction with immune checkpoint blockade: ipilimumab 3mg/kg on day 1, pilimumab 3mg/kg plus nivolumab 1mg/kg on day 22, and nivolumab 3mg/kg on day 43

Response evaluation after the last cycle of checkpoint inhibition.

Chemoradiation will start 10-12 weeks after start of checkpoint inhibition according to the following scheme:

* Mitoycine C (12mg/m2) on the first day of radiotherapy, followed by either 5-fluorouracil intravenously (500mg/m2) five days a week during week one and four of radiation, or oral capecitabin (2x825mg/m2) every day during the radiation period
* Radiation with a preference for a four-week schedule, in which 55 Gy will be administered using intensity modulated radiation therapy

Ipilimumab + nivolumab

This is a single-armed, multicenter, non-blinded phase 2 study to assess efficacy of induction ipilimumab + nivolumab followed by chemoradiation to spare the bladder in urothelial bladder cancer.

This is a phase 2 study in which fifty adult patients with cT2-4aN0-2 urothelial bladder cancer, who are amenable for chemoradiation, will be included. Lymph nodes should be amenable for inclusion into the radiation field.

Included patients will be treated with three cycles of checkpoint inhibition: ipilimumab 3mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43.

Response of this induction therapy will be evaluated by cystoscopy, mpMRI and a CT scan.

Patients will then be treated by radiation to the bladder and involved nodes, in combination with mitomycine C (day 1, 12 mg/m2, maximum dose of 20 mg) and either daily capecitabin or intravenous 5-FU in week 1 and 4. Radiotherapy will be delivered using Volumetric Modulated Arc Therapy delivering a dose of 50Gy to the whole bladder with a simultaneous tumor boost of 60Gy to the tumor bed.

The primary endpoint is efficacy, defined as bladder-intact event-free survival (BI-EFS). Events consist of death by any cause; muscle-invasive, upper urinary tract, nodal or distant recurrence, cystectomy, or switch to cisplatin-based chemotherapy.

The first evaluation after completion of chemoradiation will be after three months. Further follow-up visits will take place 6, 12, 18, 24, 30, and 36 months after completion of chemoradiation. During these visits, focused physical examination, cystoscopy and a CT chest-abdomen will be performed, combined with registration of treatment-related adverse events and a questionnaire for evaluating QoL, bladder function and long-term effects of immunotherapy on QoL.

Key secondary endpoints are overall survival (OS), recurrence-free survival (RFS), feasibility to proceed to chemoradiation, safety, QoL, and bladder function.

Multicenter, open-label, phase 2 clinical trial

Checkpoint Inhibition and Chemoradiotherapy as Bladder Sparing Treatment in UC

A Phase 2 Clinical Study to Assess Efficacy of Induction Ipilimumab/Nivolumab to Spare the Bladder in Urothelial Bladder Cancer

Tumor evaluation by AI based radiological assessment of pre- and on-treatment mpMRI will be established to identify nonresponding patients. BI-EFS, RFS and OS will be compared for the binary outcome mpMRI response vs nonresponse.

BI-EFS, RFS and OS will be compared between patients with Tumor mutational burden (TMB) \>median vs \<median.

BI-EFS, RFS and OS will be compared between patients with PD-L1 high tumors versus patients with PD-L1 low tumors.

Events are defined as death by any cause, muscle-invasive, upper urinary tract, nodal or distant recurrence, cystectomy, or switch to cisplatin-based chemotherapy.

RFS is defined as time from start of therapy until the following events: muscle-invasive bladder or upper urinary tract recurrence, locoregional or distant metastases, switch to cisplatin-based chemotherapy or death by any cause.

OS is defined as the time between the date of enrollment and the date of death.

Percentage of patients able to proceed to CRT

QoL will be assessed using the EORTC QLQ-C30 and an unvalidated immunotherapy-related QoL questionnaire developed by and used in the Netherlands Cancer Institute. These will be provided to evaluate changes from baseline in QoL and evaluate long-term effects of immunotherapy on QoL using both multi-item scale and single-item scales. A graph showing the change from baseline to three timepoints will be reported: 56 ±7 days after treatment initiation and at 3, 6, 12,18 and 24 months after finalizing chemoradiotherapy.

Questionnaires for bladder function (EORTC-QLQ-BLM30)will be provided, resulting in a score on a four point scale. A graph showing the change from baseline to six timepoints will be reported: 56 ±7 days after treatment initiation and at 3, 6, 12,18 and 24 months after finalizing chemoradiotherapy.

Bristol-Myers Squibb

The Netherlands Cancer Institute

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Pembrolizumab

Immunomodulating Agents

Trametinib

Dabrafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receiving ipilimumab + nivolumab

Dabrafenib + trametinib

Novartis Pharmaceuticals

This was a retrospective cohort study using the PharMetrics database. The analysis was conducted using the most recent 5 years of data from the database, January 1, 2015, to October 30, 2020. Included patients were followed for outcome evaluation from the index date (first prescription of treatment, immunotherapy \[IO\], or targeted therapy \[TT\] following diagnosis of non-metastatic malignant melanoma and evidence of first lymph node resection), until the first occurrence or end of continuous eligibility or end of the study period.

Retrospective Assessment of Adverse Events-related Healthcare Resource Utilization and Costs of Immune Checkpoint Inhibitor and Targeted Therapy for Adjuvant Treatment of Melanoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Checkpoint Inhibition and Chemoradiotherapy as Bladder Sparing Treatment in UC	NCT05200988	Urothelial Carc... Bladder Cancer	Ipilimumab + ni...	18 Years -	The Netherlands Cancer Institute
Retrospective Assessment of Adverse Events-related Healthcare Resource Utilization and Costs of Immune Checkpoint Inhibitor and Targeted Therapy for Adjuvant Treatment of Melanoma	NCT05714371	Melanoma	Nivolumab Ipilimumab + ni... Pembrolizumab Dabrafenib + tr...	18 Years -	Novartis
Retrospective Assessment of Adverse Events-related Healthcare Resource Utilization and Costs of Immune Checkpoint Inhibitor and Targeted Therapy for Adjuvant Treatment of Melanoma	NCT05714371	Melanoma	Nivolumab Ipilimumab + ni... Pembrolizumab Dabrafenib + tr...	18 Years -	Novartis

Spots Global Cancer Trial Database for ipilimumab + nivolumab