Impact of Chronic Renal Failure on Plasma Exposure of Kinase Inhibitors in Patients Treated for Metastatic Kidney Cancer

Study Overview
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Brief Summary
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The study of the blood concentration of ITK what are pazopanib and cabozantinib at 1 month and 3 months from the start of treatment will allow to evaluate the impact of renal failure on their efficacy and toxicity in patients with metastatic kidney cancer.

Detailed Description
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This study involves patients treated with cabozantinib or pazopanib in their metastatic renal cancer. Indeed, the aim of this study is to assess the blood concentration of these two drugs as well as their tolerance, in relation to their renal function (normal renal function or moderate or severe renal failure). Pazopanib and cabozantinib are kinase inhibitors that are indicated for a number of cancer conditions, including metastatic kidney cancer. Both of these oral therapies require a daily intake of the drug to ensure its effectiveness. For this, the patient must have optimal compliance and benefit from regular follow up to assess clinical and biological tolerance. Chronic renal failure is a factor that may impact the efficacy and toxicity of pazopanib and cabozantinib. This may be due either to a elimination default of the drug or to much elimination if the drug is filtered after dialysis. As a result, kinase inhibitors could be impacted by chronic renal failure and thus modify the safety and efficacy of the treatment. A study-specific blood test will be taken at 1 month and at 3 months during a consultation (this blood test is in addition to the routine blood test). Its analysis will evaluate the quantity of medication present in the blood. The other objective of this study is to evaluate the side effects of the drug taken by the patient (pazopanib or cabozantinib). This will alow to propose possible dose adjustments for each of these treatments and thus improve the management of these patients.

Official Title
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Study of the Impact of the Stage of Chronic Renal Failure on Plasma Exposure of Kinase Inhibitors (ITK) in Patients Treated for Metastatic Kidney Cancer

Conditions
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Kidney Neoplasm

Intervention / Treatment
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* Other: blood sampling for ITK dosage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient followed for metastatic clear cell renal cell carcinoma. Age ≥18 years old. Performance Status (PS) according to Eastern Cooperative Oncology Group (ECOG) = 0, 1 or 2 Patient treated with a VEGF-R inhibitor: pazopanib or cabozantinib for metastatic kidney cancer. If patient doesn't have renal failure -> group 1, or if patient has chronic renal failure according to the moderate stage Chronic Kidney Disease - Epidemiology (CKD-EPI) formula (Clr <60 ml / min, stage 3) -> group 2, or if patient have chronic renal failure according to the CKD-EPI formula of severe or terminal stage (Clr <30 ml / min, stage 4 and stage 5), with or without dialysis -> group 3. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. Patient having given informed, written and express consent. Affiliation to the French Social Security System. Exclusion Criteria: Indication other than clear cell renal cell carcinoma for these same ITKs Pregnant or breast-feeding subjects Patient whose regular follow-up is impossible for psychological, family, social or geographic reasons, Patient under guardianship, curatorship or safeguard of justice Participation in another clinical study with a research product during the last 30 days before inclusion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patients without renal insufficiency under pazopanib<br>Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription. | Other: blood sampling for ITK dosage<br>* Blood sample for ITK dosage at visit 1 (1 month +/- 1 week after the start of treatment) and at visit 2 (3 months +/- 1 month after the start of treatment)<br>|
| Other: Patients without renal insufficiency under cabozantinib<br>Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription. | Other: blood sampling for ITK dosage<br>* Blood sample for ITK dosage at visit 1 (1 month +/- 1 week after the start of treatment) and at visit 2 (3 months +/- 1 month after the start of treatment)<br>|
| Other: Patients with moderate renal impairment under pazopanib<br>Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription. | Other: blood sampling for ITK dosage<br>* Blood sample for ITK dosage at visit 1 (1 month +/- 1 week after the start of treatment) and at visit 2 (3 months +/- 1 month after the start of treatment)<br>|
| Other: Patients with moderate renal impairment under cabozantinib<br>Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription. | Other: blood sampling for ITK dosage<br>* Blood sample for ITK dosage at visit 1 (1 month +/- 1 week after the start of treatment) and at visit 2 (3 months +/- 1 month after the start of treatment)<br>|
| Other: Patients with severe or terminal stage renal impairment under pazopanib<br>Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription. | Other: blood sampling for ITK dosage<br>* Blood sample for ITK dosage at visit 1 (1 month +/- 1 week after the start of treatment) and at visit 2 (3 months +/- 1 month after the start of treatment)<br>|
| Other: Patients with severe or terminal stage renal impairment under cabozantinib<br>Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription. | Other: blood sampling for ITK dosage<br>* Blood sample for ITK dosage at visit 1 (1 month +/- 1 week after the start of treatment) and at visit 2 (3 months +/- 1 month after the start of treatment)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual concentration at equilibrium of ITK in the blood | Assessment in patients treated for metastatic kidney cancer without or with moderate or severe renal impairment if the plasma concentration (residual concentration at equilibrium) of ITK is higher than the target concentration (specific to the ITK molecule : pazopanib : 20 000 ng/mL and cabozantinib : 1000 ng/mL ) | at 1 month (+/1 week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of ITK in the blood in patients with Failure renal function | Assessment the plasma concentration (residual concentration at equilibrium) of ITK (pazopanib and / or cabozantinib) in patients with moderate renal impairment and / or severe renal impairment | at 1 month (+/- 1 week) and 3 months (+/- 1 month) | 
| Concentration of ITK in the blood in patients with normal renal function | Assessment the plasma concentration (residual concentration at equilibrium) of ITK (pazopanib and / or cabozantinib) in patients with normal renal function | at 1 month (+/- 1 week) and 3 months (+/- 1 month) | 
| Toxicities related to the intake of ITKs | Assessment toxicities induced by the use of ITK targeting Vascular Endothelial Growth Factor-Receptor (VEGF-R) by using the NCI-CTCAE version 5.0 (grade ≥ 2) | at 1 month (+/- 1 week) and 3 months (+/- 1 month) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic kidney cancer, pazopanib, cabozantinib, renal failure