Retrospective Study on the Safety of Nivolumab in Patients With mRCC and Renal Failure
- Conditions
- Metastatic Renal Cell Carcinoma
- Registration Number
- NCT07117409
- Lead Sponsor
- Azienda USL Reggio Emilia - IRCCS
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 81
- 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.
- patients who have received immunotherapy under EAP (Expanded Access Programm) or other clinical trials;
- dialysis patients.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Treatment safety At study completion (up to 16 months) To describe the safety of the treatment, the number of adverse events will be counted percentage, grade 1-2 and 3-4 and will compare for the 3 patient stratification groups.
- Secondary Outcome Measures
Name Time Method Effectiveness of the treatment At study completion (up to 16 months) The effectiveness of treatment in the population in terms of objective responses will be described (ORR) defined as number of patients in complete response, partial response established by clinicians according to RECIST 1.1 criteria. Objective response rates will be compared between the three groups of patient stratification.
Survival assessment At study completion (up to 16 months) It will describe the possible correlation between the three patient stratification groups and the survival. The overall survival estimate is defined as the time from treatment start date to date of death from any cause. Survival time comes discontinued at the date of the last follow-up visit for patients alive or lost to follow-up.
Evaluation of progression free time At study completion (up to 16 months) The possible correlation between the three patient stratification groups and the progression free survival (PFS) will be described. The PFS estimate is defined as the time from the start date of treatment at the date of disease progression. Time to progression is interrupted at date of last follow-up visit for patients not progressed.
Trial Locations
- Locations (1)
Azienda USL IRCCS di Reggio Emilia
🇮🇹Reggio Emilia, Italy
Azienda USL IRCCS di Reggio Emilia🇮🇹Reggio Emilia, Italy