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

NCT ID: NCT04823923

Last Updated: 2025-02-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-06

Study Completion Date

2026-03-31

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.

Conditions

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Kidney Neoplasm

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Patients without renal insufficiency under pazopanib

Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription.

Group Type OTHER

blood sampling for ITK dosage

Intervention Type OTHER

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)

Patients without renal insufficiency under cabozantinib

Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription.

Group Type OTHER

blood sampling for ITK dosage

Intervention Type OTHER

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)

Patients with moderate renal impairment under pazopanib

Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription.

Group Type OTHER

blood sampling for ITK dosage

Intervention Type OTHER

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)

Patients with moderate renal impairment under cabozantinib

Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription.

Group Type OTHER

blood sampling for ITK dosage

Intervention Type OTHER

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)

Patients with severe or terminal stage renal impairment under pazopanib

Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription.

Group Type OTHER

blood sampling for ITK dosage

Intervention Type OTHER

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)

Patients with severe or terminal stage renal impairment under cabozantinib

Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription.

Group Type OTHER

blood sampling for ITK dosage

Intervention Type OTHER

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)

Interventions

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blood sampling for ITK dosage

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)

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Patient followed for metastatic clear cell renal cell carcinoma.
2. Age ≥18 years old.
3. Performance Status (PS) according to Eastern Cooperative Oncology Group (ECOG) = 0, 1 or 2
4. Patient treated with a VEGF-R inhibitor: pazopanib or cabozantinib for metastatic kidney cancer.
5. 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.
6. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
7. Patient having given informed, written and express consent.
8. Affiliation to the French Social Security System.

Exclusion Criteria

1. Indication other than clear cell renal cell carcinoma for these same ITKs
2. Pregnant or breast-feeding subjects
3. Patient whose regular follow-up is impossible for psychological, family, social or geographic reasons,
4. Patient under guardianship, curatorship or safeguard of justice
5. Participation in another clinical study with a research product during the last 30 days before inclusion.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ligue contre le cancer, France

OTHER

Sponsor Role collaborator

Institut du Cancer de Montpellier - Val d'Aurelle

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fanny LEENHARDT, Dr

Role: PRINCIPAL_INVESTIGATOR

Institut du Cancer de Montpellier (ICM)

Locations

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APHM Hôpital LA TIMONE

Marseille, , France

Site Status RECRUITING

CHU Montpellier - Hôpital St Eloi

Montpellier, , France

Site Status RECRUITING

ICM Val d'Aurelle

Montpellier, , France

Site Status RECRUITING

CHU de Nîmes, Institut de Cancérologie du Gard

Nîmes, , France

Site Status RECRUITING

Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole

Toulouse, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Aurore MOUSSION

Role: CONTACT

04 67 61 31 02 ext. +33

Emmanuelle TEXIER

Role: CONTACT

04 67 61 31 02 ext. +33

Facility Contacts

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Laurent DEVILLE, Dr

Role: primary

04 91 38 57 08 ext. +33

Delphine TOPART, Dr

Role: primary

04 67 33 01 37 ext. +33

Fanny LEENHARDT, Dr

Role: primary

04 67 61 24 77 ext. +33

Nadine HOUEDE, Pr

Role: primary

04 66 68 33 01 ext. +33

Loïc MOUREY, Dr

Role: primary

05 31 15 51 67 ext. +33

References

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van Erp NP, Gelderblom H, Guchelaar HJ. Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5.

Reference Type BACKGROUND
PMID: 19733976 (View on PubMed)

Hendrayana T, Wilmer A, Kurth V, Schmidt-Wolf IG, Jaehde U. Anticancer Dose Adjustment for Patients with Renal and Hepatic Dysfunction: From Scientific Evidence to Clinical Application. Sci Pharm. 2017 Feb 27;85(1):8. doi: 10.3390/scipharm85010008.

Reference Type BACKGROUND
PMID: 28264440 (View on PubMed)

Verheijen RB, Bins S, Mathijssen RH, Lolkema MP, van Doorn L, Schellens JH, Beijnen JH, Langenberg MH, Huitema AD, Steeghs N; Dutch Pharmacology Oncology Group. Individualized Pazopanib Dosing: A Prospective Feasibility Study in Cancer Patients. Clin Cancer Res. 2016 Dec 1;22(23):5738-5746. doi: 10.1158/1078-0432.CCR-16-1255. Epub 2016 Jul 28.

Reference Type BACKGROUND
PMID: 27470967 (View on PubMed)

Lacy S, Yang B, Nielsen J, Miles D, Nguyen L, Hutmacher M. A population pharmacokinetic model of cabozantinib in healthy volunteers and patients with various cancer types. Cancer Chemother Pharmacol. 2018 Jun;81(6):1071-1082. doi: 10.1007/s00280-018-3581-0. Epub 2018 Apr 23.

Reference Type BACKGROUND
PMID: 29687244 (View on PubMed)

Other Identifiers

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2020-A01533-36

Identifier Type: OTHER

Identifier Source: secondary_id

PROICM 2020-08 IRE

Identifier Type: -

Identifier Source: org_study_id

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