Retrospective Study on the Safety of Nivolumab in Patients With mRCC and Renal Failure

NCT ID: NCT07117409

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 81 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-06-29
• Study Completion Date: 2025-06-30

Brief Summary

This is an observational, retrospective, multicenter study aimed to compare the toxicity of Nivolumab in patients with metastatic renal cell carcinoma treated in line II and III stratified into 3 patient groups:

• patients with normal or mildly reduced renal function (GFR<90 and ≥60 ml/min/1.73 m^2);
• patients with moderate renal impairment (GFR <60 e ≥30 ml/min/1.73 m^2),
• patients with severe renal impairment (GFR <30 e ≥15 ml/min/1.73 m^2) Patients must have been treated with Nivolumab, as per clinical practice. All patients who have received at least one drug administration between february 2017 to December 31, 2018 will be enrolled in the study.

Detailed Description

The treatment of metastatic renal cancer has undergone several changes in recent years especially regarding second line treatment which has seen the development of new ones antiangiogenic drugs such as cabozantinib and immunotherapy with inhibitory checkpoints (nivolumab). Nivolumab is a human IgG4 monoclonal antibody that binds to the receptor 'programmed-death' 1 (PD-1) by blocking its interaction with its ligand (PD-L1). The PD-1 receptor has an action negative regulatory on T lymphocyte activity, the interaction between receptor and ligand (PD-L1) expressed by cancer cells involves inhibition of T cell proliferation and cytokine secretion. The metabolism of Nivolumab was not well characterized, although it is probably degraded into small peptides and amino acids through catabolic pathways similar way to endogenous IgG; all this is important as there is no involvement by normal excretory/emuntory organs such as liver and kidney. The patient affected by metastatic renal cell carcinoma presents more frequently than a subject of the same sex and age a picture of concomitant renal insufficiency (IR); this data could be linked to age median at diagnosis (65 years), high incidence of diabetes and arterial hypertension, and presence of a previous nephrectomy .Renal impairment (IR) is classified as: - mild (glomerular filtrate (GFR) <90 and ≥60 ml/min/1.73 m^2); - moderate (GFR <60 and ≥30 ml/min/1.73 m^2), or severe (GFR <30 and ≥15 ml/min/1.73 m^2) Some pharmacokinetic analyses have been conducted for patients with mild renal impairment or moderate who have not documented clinically detected differences in clearance of Nivolumab compared to patients with normal renal function; however this is a number very modest number of patients with moderate IR and an even more limited number of patients with severe IR such that these results cannot be considered conclusive; the studies in fact, registrars did not include patients with severe IR or on dialysis. Only some case reports of patients with severe renal insufficiency treated are described in the literature with inhibitory immunocheckpoints without this leading to aggravation of renal function baseline or changes efficacy or toxicity; however few of these reported cases involve patients with metastatic renal cell carcinoma. And' instead, a case of a patient with renal neoplasm in hemodialysis treatment with benefit in terms of objective response from nivolumab therapy. it is also known from the analysis conducted on patients treated with nivolumab within the EAP in Italy, that this drug has a benefit in terms of effectiveness and safety even for older patients, who represent only a small share of the population of pivotal studies; such patients may more frequently have both by age and by comorbidity a reduction in basic renal function. Aim of our retrospective study is to assess whether there are differences in the profile of toxicity in renal cell carcinoma patients treated with Nivolumab in line II or III based on renal function. Patients will be stratified in 3 patient groups:

• patients with normal or mildly reduced renal function (GFR<90 and ≥60 ml/min/1.73 m^2);
• patients with moderate renal failure (GFR <60 e ≥30 ml/min/1.73 m^2),
• patients with severe renal failure (GFR <30 e ≥15 ml/min/1.73 m^2).

Conditions

Metastatic Renal Cell Carcinoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Patients with normal or mildly reduced renal function (GFR<90 and ≥60 ml/min/1.73 m^2)

No interventions assigned to this group

Patients with moderate renal failure (GFR <60 e ≥30 ml/min/1.73 m^2)

No interventions assigned to this group

Patients with severe renal failure (GFR <30 e ≥15 ml/min/1.73 m^2)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• signing informed consent, in case of patients still alive;
• histologically confirmed diagnosis of metastatic renal cell carcinoma;
• at least one administration of Nivolumab therapy, in the second-or third line of treatment february 2017 to December 31, 2018;
• availability of inpatient and/or outpatient medical records for clinical data collection.

Exclusion Criteria

• patients who have received immunotherapy under EAP (Expanded Access Programm) or other clinical trials;
• dialysis patients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda USL Reggio Emilia - IRCCS

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, , Italy

Countries

Italy

References

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Other Identifiers

622/2019/OSS/IRCCSRE

Identifier Type: -

Identifier Source: org_study_id