Targeted therapy drug monitoring in digestive oncology: Dosage of plasma levels of various multikinase inhibitors (MKI) in patients treated for advanced digestive cancer (gastrointestinal stromal tumor (GIST), metastatic colorectal cancer (mCRC), hepatocellular carcinoma (HCC), gastroenteropancreatic neuroendocrine tumor (gepNET), or pancreatic neuroendocrine tumor (pNET)), with the aim of determine the optimal dose adapted for each patient, in the future.
Phase IV, national, multicenter, open, multi-cohort interventional study: 1. Regorafenib - mCRC, GIST, and HCC = 3x30 = 90 patients 2. Everolimus - gepNET = 60 patients 3. Sunitinib - pNET and GIST = 60 patients 4. Cabozantinib - HCC = 60 patients 5. Encorafenib-cetuximab - mCRC = 60 patients The patients included will be treated and followed according to standard practice (national recommendations and according to the summary of product characteristics (SmPC) of each molecule). According to the cohort, a maximum of 1 to 2 blood tubes will be taken at different times during the study: at baseline, then 1 month after the start of treatment, then 2 months after the start of treatment, if an adverse event of specific interest (AESI) occurs, and in case of progressive disease.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
330
Determine for each drug plasmatic exposure (Css, trough) through the PopPK model. Concentrations measured at the following time points: * 1 month after the first treatment administration * 2 months after the first treatment administration * In case of progression * In case of severe toxicities (AESI) related to the drug received
CHU d'Amiens Pcardie - Hopital Sud
Amiens, France
RECRUITINGCH d'Auxerre
Auxerre, France
RECRUITINGInstitut du Cancer Avignon - Institut Sainte Catherine
Avignon, France
WITHDRAWNCH de Bayeux - Onconormandie
Bayeux, France
WITHDRAWNCentre Jean Perrin
Clermont-Ferrand, France
RECRUITINGHôpital Beaujon APHP
Clichy, France
RECRUITINGCentre Georges Francois Leclerc
Dijon, France
WITHDRAWNInstitut de Cancérologie de Bourgogne
Dijon, France
RECRUITINGCH Eure Seine - Hopital d'Evreux Vernon
Évreux, France
NOT_YET_RECRUITINGCentre Oscar Lambret
Lille, France
RECRUITING...and 19 more locations
Trough concentration (Ctrough)
Trough concentration (Ctrough) shows the blood concentration reached by a drug immediately before the next dose is administered, once steady state has been attained. It can also be defined as the minimal drug concentration in the patient's body. Plasmatic measures will be performed by liquid chromatography with tandem mass spectrometry after protein precipitation by acetonitrile.
Time frame: From inclusion untill the end of treatment up to 4 years
Progression-free survival
Progression-free survival (PFS) is the lenght of the time between inclusion and the first event of disease progression or death whatever the cause.
Time frame: 4 years
Overall survival
Overall survival (OS) is the lenght of time between inclusion and death whatever the cause.
Time frame: 4 years
Objective response rate
Objective response rate (ORR) is the percentage of patients with a best response during treatment being either complete response (CR) or partial response (PR).
Time frame: 4 years
Disease control rate
Disease control rate (DCR) is defined as the percentage of patients with a best response during treatment being either CR, PR, or Stable Disease (SD).
Time frame: 4 years
Safety: drug toxicity
Drug toxicity occurrence related to standard treatment will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. NCI-CTCAE is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders. Only AE of Specific Interest (AESI) will be collected. An AESI is an AE related to treatment that is: * G3 or G4 according to NCI-CTCAE version 5.0, or * Leading to treatment modification (dose reduction or treatment interruption), or * Categorized as serious adverse event (SAE) by the investigator, or * Considered as clinically significant by the investigator.
Time frame: Throughout study completion, up to 4 years
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