Clinical trial NCT02404584: The Pharmacokinetic Variability of Sunitinib in Patients With Metastatic Renal Cancer
Official title: The Pharmacokinetic Variability of Sunitinib in Patients With Metastatic Renal Cancer: Searching for Pharmacogenetic Determinants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Neoplasms
Keywords: Metastatic kidney cancer
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2015-03-31
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population consisted of patients with renal cell carcinoma treated with sunitinib (Sutent).

Brief summary: The primary objective of this study is to determine the percentage of patients with a plasma concentration of sunitinib remaining at equilibrium (\[Suni\]REq) greater than 100 ng / ml (effective concentration according to the current literature).

Detailed description: The secondary objectives of this study are:

* To describe the distribution of constitutional genetic determinants related to sunitinib pharmacokinetics, and to study their correlation with

  * the \[Suni\]REq,
  * the advent of toxicity,
  * the tumor response.
* To describe the variation in the \[Suni\]REq and the plasma concentration of the active entity remaining at equilibrium (\[ActEnt\]REq) at:

  * the interindividual level,
  * overtime, between chemotherapy cycles.
* To describe the variation in the ratio of the plasma concentration of the metabolite remaining at equilibrium (\[Metab\]REq) to the \[Suni\]REq at:

  * the interindividual level,
  * overtime, between chemotherapy cycles.
* To explore potential correlations between the \[Suni\]REq and

  * toxicity,
  * tumor response.
* To explore potential correlations between the \[ActEnt\]REq and

  * toxicity,
  * tumor response.
* To explore potential correlations between the ratio \[Metab\]REq / \[Suni\]REq and

  * toxicity,
  * tumor response.

Eligibility criteria: Inclusion Criteria:

* The patient was correctly informed concerning the implementation of the study, its objectives, constraints and patient rights
* The patient must have given his/her informed and signed consent
* The patient must be insured or beneficiary of a health insurance plan
* The patient has kidney cancer and should begin treatment with sunitinib (Sutent) at the time of inclusion

Exclusion Criteria:

* The patient started treatment with sunitinib (Sutent) before inclusion
* The patient is participating in another interventional study
* The patient has participated in another interventional study within the last month
* The patient is in an exclusion period determined by a previous study
* The patient is under judicial protection, under tutorship or curatorship
* The patient refuses to sign the consent
* It is impossible to correctly inform the patient
* The patient is pregnant, parturient, or breastfeeding
* The patient has a contraindication (or an incompatible drug combination) for a treatment used in this study

Primary outcomes:
measure: The percentage of patients with a plasma concentration of sunitinib remaining at equilibrium ([Suni]REq) greater than 100 ng / ml
timeFrame: Between C1D15* and C1D28*
Secondary outcomes:
measure: Genotype: genetic polymorphisms of enzymes of phase I, phase II (conjugation), carriers of Phases 0 and III, the nuclear receptors PXR and CAR, pharmacological targets of sunitinib (tyrosine kinase receptors).
timeFrame: Baseline (day 0)
measure: [Suni]REq per cure
timeFrame: Between CmD15* and CmD28* for 18 months
measure: The presence/absence of grade I, II, III, IV, V (CTCAE version 4.0) toxicities per cure
timeFrame: 18 months
measure: Tumor response per cure
timeFrame: 18 months
measure: Toxicity (yes/no) for each type of toxic event per cure
timeFrame: Between CmD15* and CmD28* for 18 months
measure: [Suni]REq at the 1st cure, averaged per initial dosing (37.5mg, 50 mg, 75 mg, 100mg)
timeFrame: Between C1D15* and C1D28*
measure: the average [Suni]REq over all cures
timeFrame: 18 months
measure: For each cure, the average [Suni]REq for cure 1 to cure m
timeFrame: 18 months
measure: For each cure, the ratio of the plasma concentration of the metabolite remaining at equilibrium ([Metab]REq) / [Suni]REq
timeFrame: Between CmD15* and CmD28* for 18 months
measure: [Metab]REq / [Suni]REq
timeFrame: Between C1D15* and C1D28*
measure: [Metab]REq / [Suni]REq averaged per initial dosing
timeFrame: Between C1D15* and C1D28*
measure: Mean [Metab]REq / [Suni]REq for all cures
timeFrame: 18 months
measure: For each cure, the average [Metab]REq / [Suni]REq for cure 1 to cure m
timeFrame: 18 months
measure: For each cure, the plasma concentration of the active entity remaining at equilibrium ([ActEnt]REq)
timeFrame: 18 months
measure: [ActEnt]REq
timeFrame: Between C1D15* and C1D28*
measure: [ActEnt]REq averaged per initial dosing
timeFrame: Between C1D15* and C1D28*
measure: Mean [ActEnt]REq for all cures
timeFrame: 18 months
measure: For each cure, the average [ActEnt]REq for cure 1 to cure m
timeFrame: 18 months
measure: For each cure, the % of patients whose dosings were modified since the beginning of the study
timeFrame: 18 months
measure: Presence/absence of side effects noted in the summary of product characteristics for sunitinib
timeFrame: 18 months
Other outcomes:
Locations:
city: Montpellier cedex 5
country: France
facility: CHRU de Montpellier - Hôpital Saint-Eloi
city: Nîmes Cedex 09
country: France
facility: CHRU de Nîmes - Hôpital Universitaire Carémeau
city: Nîmes Cedex 9
country: France
facility: Institut de Cancérologie du Gard (ICG)
Study officials:
affiliation: Centre Hospitalier Universitaire de Nîmes
name: Litaty Mbatchi, PharmD
role: STUDY_DIRECTOR
References: