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

NCT04823923 | Recruiting

• 2 other identifiers: PROICM 2020-08 IRE2020-A01533-36
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Kidney Neoplasm

Keywords

metastatic kidney cancer; pazopanib; cabozantinib; renal failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Concentration of ITK in the blood in patients with Failure renal function

  at 1 month (+/- 1 week) and 3 months (+/- 1 month)

• Concentration of ITK in the blood in patients with normal renal function

  at 1 month (+/- 1 week) and 3 months (+/- 1 month)

• Toxicities related to the intake of ITKs

  at 1 month (+/- 1 week) and 3 months (+/- 1 month)

Study Arms (6)

Patients without renal insufficiency under pazopanib

OTHER

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

Other: blood sampling for ITK dosage

Patients without renal insufficiency under cabozantinib

OTHER

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

Other: blood sampling for ITK dosage

Patients with moderate renal impairment under pazopanib

OTHER

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

Other: blood sampling for ITK dosage

Patients with moderate renal impairment under cabozantinib

OTHER

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

Other: blood sampling for ITK dosage

Patients with severe or terminal stage renal impairment under pazopanib

OTHER

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

Other: blood sampling for ITK dosage

Patients with severe or terminal stage renal impairment under cabozantinib

OTHER

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

Other: blood sampling for ITK dosage

Interventions

blood sampling for ITK dosage 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; Patients with moderate renal impairment under pazopanib; Patients with severe or terminal stage renal impairment under cabozantinib; Patients with severe or terminal stage renal impairment under pazopanib; Patients without renal insufficiency under cabozantinib; Patients without renal insufficiency under pazopanib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead
• Ligue contre le cancer, France: collaborator

Study Sites (5)

APHM Hôpital LA TIMONE

Marseille, 13005, France

RECRUITING

CHU Montpellier - Hôpital St Eloi

Montpellier, 34295, France

RECRUITING

ICM Val d'Aurelle

Montpellier, 34298, France

RECRUITING

CHU de Nîmes, Institut de Cancérologie du Gard

Nîmes, 30029, France

RECRUITING

Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole

Toulouse, 31059, France

RECRUITING

Related Publications (4)

• 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.

  PMID: 19733976 BACKGROUND

• 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.

  PMID: 28264440 BACKGROUND

• 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.

  PMID: 27470967 BACKGROUND

• 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.

  PMID: 29687244 BACKGROUND

MeSH Terms

Conditions

Kidney Neoplasms; Renal Insufficiency

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Fanny LEENHARDT, Dr

  Institut du Cancer de Montpellier (ICM)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aurore MOUSSION

CONTACT

04 67 61 31 02; DRCI-icm105@icm.unicancer.fr

Emmanuelle TEXIER

CONTACT

04 67 61 31 02; DRCI-icm105@icm.unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: April 1, 2021
• Study Start: December 6, 2021
• Primary Completion: January 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)