The Pharmacokinetic Variability of Sunitinib in Patients With Metastatic Renal Cancer
- Conditions
- Kidney Neoplasms
- Registration Number
- NCT02404584
- Lead Sponsor
- Centre Hospitalier Universitaire de Nīmes
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The percentage of patients with a plasma concentration of sunitinib remaining at equilibrium ([Suni]REq) greater than 100 ng / ml Between C1D15* and C1D28* \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
- Secondary Outcome Measures
Name Time Method Mean [Metab]REq / [Suni]REq for all cures 18 months Toxicity (yes/no) for each type of toxic event per cure Between CmD15* and CmD28* for 18 months \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
For each cure, the average [Suni]REq for cure 1 to cure m 18 months 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). Baseline (day 0) Predefined list of genes:
ABCB1 ABCC2 ABCG2 CYP1A1 CYP1A2 CYP2A6 CYP2B6 CYP2C19 CYP2C8 CYP2C9 CYP2D6 CYP2E1 CYP3A4 CYP3A5 NR1I2 NR1I3 SLC15A2 SLC22A1 SLC22A2 SLC22A6 SLCO1B1 SLCO1B3 SULT1A1 UGT1A1 UGT2B15 UGT2B17 UGT2B7 VEGFR1,2,3 PDGFR-α et β KIT[Suni]REq at the 1st cure, averaged per initial dosing (37.5mg, 50 mg, 75 mg, 100mg) Between C1D15* and C1D28* \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
the average [Suni]REq over all cures 18 months For each cure, the average [ActEnt]REq for cure 1 to cure m 18 months For each cure, the ratio of the plasma concentration of the metabolite remaining at equilibrium ([Metab]REq) / [Suni]REq Between CmD15* and CmD28* for 18 months \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
[ActEnt]REq Between C1D15* and C1D28* \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
Presence/absence of side effects noted in the summary of product characteristics for sunitinib 18 months The presence/absence of grade I, II, III, IV, V (CTCAE version 4.0) toxicities per cure 18 months [Metab]REq / [Suni]REq Between C1D15* and C1D28* \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
[Metab]REq / [Suni]REq averaged per initial dosing Between C1D15* and C1D28* \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
For each cure, the average [Metab]REq / [Suni]REq for cure 1 to cure m 18 months For each cure, the plasma concentration of the active entity remaining at equilibrium ([ActEnt]REq) 18 months For each cure, the % of patients whose dosings were modified since the beginning of the study 18 months [Suni]REq per cure Between CmD15* and CmD28* for 18 months \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
[ActEnt]REq averaged per initial dosing Between C1D15* and C1D28* \*Each patient will undergo several cycles of treatment with sunitinib during the monitoring period as part of routine care (= 18 months; the number of cycles per patient can vary, which is normal). Each cycle and each day of the cycle will be annotated with the letters C and D, respectively, followed by a number in chronological order. Thus C1D1 refers to to the first day of the first cycle; CmDn will be the nth day of the mth cycle.
Tumor response per cure 18 months Mean [ActEnt]REq for all cures 18 months
Trial Locations
- Locations (3)
CHRU de Montpellier - Hôpital Saint-Eloi
🇫🇷Montpellier cedex 5, France
CHRU de Nîmes - Hôpital Universitaire Carémeau
🇫🇷Nîmes Cedex 09, France
Institut de Cancérologie du Gard (ICG)
🇫🇷Nîmes Cedex 9, France
CHRU de Montpellier - Hôpital Saint-Eloi🇫🇷Montpellier cedex 5, France