search
Back to results

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

Primary Purpose

Kidney Neoplasm

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
blood sampling for ITK dosage
Sponsored by
Institut du Cancer de Montpellier - Val d'Aurelle
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Kidney Neoplasm focused on measuring metastatic kidney cancer, pazopanib, cabozantinib, renal failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • APHM Hôpital LA TIMONERecruiting
  • CHU Montpellier - Hôpital St EloiRecruiting
  • ICM Val d'AurelleRecruiting
  • CHU de Nîmes, Institut de Cancérologie du GardRecruiting
  • Institut Universitaire du Cancer de Toulouse (IUCT) OncopoleRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Other

Other

Other

Other

Other

Other

Arm Label

Patients without renal insufficiency under pazopanib

Patients without renal insufficiency under cabozantinib

Patients with moderate renal impairment under pazopanib

Patients with moderate renal impairment under cabozantinib

Patients with severe or terminal stage renal impairment under pazopanib

Patients with severe or terminal stage renal impairment under cabozantinib

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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 )

Secondary Outcome Measures

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
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
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)

Full Information

First Posted
March 22, 2021
Last Updated
October 19, 2023
Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
Collaborators
Ligue contre le cancer, France
search

1. Study Identification

Unique Protocol Identification Number
NCT04823923
Brief Title
Impact of Chronic Renal Failure on Plasma Exposure of Kinase Inhibitors in Patients Treated for Metastatic Kidney Cancer
Acronym
IREKI
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 6, 2021 (Actual)
Primary Completion Date
January 2026 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
Collaborators
Ligue contre le cancer, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Neoplasm
Keywords
metastatic kidney cancer, pazopanib, cabozantinib, renal failure

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients without renal insufficiency under pazopanib
Arm Type
Other
Arm Description
Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription.
Arm Title
Patients without renal insufficiency under cabozantinib
Arm Type
Other
Arm Description
Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription.
Arm Title
Patients with moderate renal impairment under pazopanib
Arm Type
Other
Arm Description
Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription.
Arm Title
Patients with moderate renal impairment under cabozantinib
Arm Type
Other
Arm Description
Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription.
Arm Title
Patients with severe or terminal stage renal impairment under pazopanib
Arm Type
Other
Arm Description
Pazopanib is taken daily, for a minimum of 3 months, according to the medical prescription.
Arm Title
Patients with severe or terminal stage renal impairment under cabozantinib
Arm Type
Other
Arm Description
Cabozantinib is taken daily, for a minimum of 3 months, according to the medical prescription.
Intervention Type
Other
Intervention Name(s)
blood sampling for ITK dosage
Intervention Description
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)
Primary Outcome Measure Information:
Title
Residual concentration at equilibrium of ITK in the blood
Description
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 )
Time Frame
at 1 month (+/1 week)
Secondary Outcome Measure Information:
Title
Concentration of ITK in the blood in patients with Failure renal function
Description
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
Time Frame
at 1 month (+/- 1 week) and 3 months (+/- 1 month)
Title
Concentration of ITK in the blood in patients with normal renal function
Description
Assessment the plasma concentration (residual concentration at equilibrium) of ITK (pazopanib and / or cabozantinib) in patients with normal renal function
Time Frame
at 1 month (+/- 1 week) and 3 months (+/- 1 month)
Title
Toxicities related to the intake of ITKs
Description
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)
Time Frame
at 1 month (+/- 1 week) and 3 months (+/- 1 month)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aurore MOUSSION
Phone
04 67 61 31 02
Ext
+33
Email
DRCI-icm105@icm.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Emmanuelle TEXIER
Phone
04 67 61 31 02
Ext
+33
Email
DRCI-icm105@icm.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fanny LEENHARDT, Dr
Organizational Affiliation
Institut du Cancer de Montpellier (ICM)
Official's Role
Principal Investigator
Facility Information:
Facility Name
APHM Hôpital LA TIMONE
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurent DEVILLE, Dr
Phone
04 91 38 57 08
Ext
+33
Email
jean-laurent.deville@ap-hm.fr
Facility Name
CHU Montpellier - Hôpital St Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Delphine TOPART, Dr
Phone
04 67 33 01 37
Ext
+33
Email
d-topart@chu-montpellier.fr
Facility Name
ICM Val d'Aurelle
City
Montpellier
ZIP/Postal Code
34298
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fanny LEENHARDT, Dr
Phone
04 67 61 24 77
Ext
+33
Email
Fanny.Leenhardt@icm.unicancer.fr
Facility Name
CHU de Nîmes, Institut de Cancérologie du Gard
City
Nîmes
ZIP/Postal Code
30029
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadine HOUEDE, Pr
Phone
04 66 68 33 01
Ext
+33
Email
nadine.houede@chu-nimes.fr
Facility Name
Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Loïc MOUREY, Dr
Phone
05 31 15 51 67
Ext
+33
Email
mourey.loic@iuct-oncopole.fr

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.
Citations:
PubMed Identifier
19733976
Citation
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.
Results Reference
background
PubMed Identifier
28264440
Citation
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.
Results Reference
background
PubMed Identifier
27470967
Citation
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.
Results Reference
background
PubMed Identifier
29687244
Citation
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs