TARGETMONITO: TARGETed Therapy Drug MONITOring in DIGestive Oncology

Sponsor

UNICANCER (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05443087

Collaborator

(none)

330

Enrollment

Locations

Arms

58.5

Anticipated Duration (Months)

13.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Digestive Cancer Metastatic Colorectal Cancer Hepatocellular Carcinoma GIST Neuroendocrine Tumors	Other: Blood sampling to build population pharmacokinetics model	N/A

Detailed Description

Phase IV, national, multicenter, open, multi-cohort interventional study:

Regorafenib - mCRC, GIST, and HCC = 3x30 = 90 patients
Everolimus - gepNET = 60 patients
Sunitinib - pNET and GIST = 60 patients
Cabozantinib - HCC = 60 patients
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 Design

Study Type:

Interventional

Anticipated Enrollment :

330 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dosing of Various Multi Kinases Inhibitors Plasma Concentrations for Patients Treated for Their Advanced Digestive Cancer, With the Aim to Determine the Best Optimal Dose for Each Treatment, in the Future

Anticipated Study Start Date :

Jul 15, 2022

Anticipated Primary Completion Date :

Jun 1, 2026

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regorafenib - mCRC, GIST, HCC 3 x 30 = 90 patients Patients with mCRC, GIST or HCC treated with Regorafenib	Other: Blood sampling to build population pharmacokinetics model 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
Experimental: Everolimus - gepNET 60 patients Patients with gepNET treated with Everolimus	Other: Blood sampling to build population pharmacokinetics model 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
Experimental: Sunitinib - pNET, GIST 2 x 30 = 60 patients Patients with pNET and GIST, treated with Sunitinib	Other: Blood sampling to build population pharmacokinetics model 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
Experimental: Cabozantinib - HCC 60 patients Patients with HCC treated with Cabozantinib	Other: Blood sampling to build population pharmacokinetics model 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
Experimental: Encorafenib - Cetuximab - mCRC 60 patients Patients with mCRC treated with the association Encorafenib - Cetuximab	Other: Blood sampling to build population pharmacokinetics model 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

Outcome Measures

Primary Outcome Measures

Trough concentration (Ctrough) [From inclusion untill the end of treatment up to 4 years]
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.

Secondary Outcome Measures

Progression-free survival [4 years]
Progression-free survival (PFS) is the lenght of the time between inclusion and the first event of disease progression or death whatever the cause.
Overall survival [4 years]
Overall survival (OS) is the lenght of time between inclusion and death whatever the cause.
Objective response rate [4 years]
Objective response rate (ORR) is the percentage of patients with a best response during treatment being either complete response (CR) or partial response (PR).
Disease control rate [4 years]
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).
Safety: drug toxicity [Throughout study completion, up to 4 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient aged 18 years or over
Advanced digestive cancer (histologically confirmed or confirmed by imaging for HCC) for which a standard treatment (according to each drug SmPC and as per standard of care) planned with:

Regorafenib for GIST, mCRC, and HCC,
Everolimus for gepNET,
Sunitinib for pNET or GIST,
Cabozantinib for HCC,
Encorafenib - cetuximab for mCRC

Life expectancy of greater than 3 months - at the discretion of the investigator
Measurable disease according to tumor evaluation criteria as per local practice (Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, etc.)
Patients must be affiliated to a Social Security System (or equivalent)
Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.

Exclusion Criteria:

Other concomitant anticancer systemic treatment (chronic chemotherapy, antitumor hormone therapy or immunotherapy) than the one studied
Unresolved toxicity higher than NCI-CTCAE v5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia and peripheral neuropathy
Prior treatment with the same MKI molecule(s) planned to be given in the cohort. If different MKI molecules (from the one(s) planned in the study) have been previously taken, a wash out period of 2 weeks before treatment should be observed.
Other invasive malignancies either currently active or active in the last 3 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell carcinoma of the skin
Any condition that may jeopardize patient participation in the study as well as non contraception for male and female with child-bearing potential, pregnancy or breast feeding.
Patient unwilling or unable to comply with the medical follow-up required by the standard treatment taken (including PK sampling during treatment phase and vital status collection during follow-up phase) because of psychosocial, familial, social or geographical reasons
Participation in another clinical study with an investigational medicinal product during the last 30 days prior to inclusion and during the present study (except if patient is included in the control arm, with placebo or with a product which have a marketed authorisation, used as per the SmPC for the given indication)
Patient deprived of their liberty or under protective custody or guardianship

Contacts and Locations

Locations

	Site	City	Country
1	CH d'Auxerre	Auxerre	France
2	Institut du Cancer Avignon - Institut Sainte Catherine	Avignon	France
3	CH de Bayeux - Onconormandie	Bayeux	France
4	Centre Jean Perrin	Clermont-Ferrand	France
5	Hôpital Beaujon APHP	Clichy	France
6	Centre Georges Francois Leclerc	Dijon	France
7	Centre Oscar Lambret	Lille	France
8	Groupement des hôpitaux de l'Institut Catholique de Lille - Hôpital Saint Vincent de Paul	Lille	France
9	Centre Léon Bérard	Lyon	France
10	Hôpital Européen Marseille	Marseille	France
11	CHRU de Nancy - Hôpital de Brabois Adulte	Nancy	France
12	CHU de Nantes - Hôtel Dieu	Nantes	France
13	Centre Antoine Lacassagne	Nice	France
14	APHP Pitié Salpétrière	Paris	France
15	Hôpital Saint Joseph	Paris	France
16	Hôpital Privé des Côtes d'Armor - SAS	Plérin	France
17	CHU de Poitiers	Poitiers	France
18	CHU de Reims - Hôpital Robert Debré	Reims	France
19	Institut Jean Godinot	Reims	France
20	Centre Eugène Marquis	Rennes	France
21	CHU Rouen - Hôpital Charles Nicolle	Rouen	France
22	CH Saint Malo - Hôpital Broussais	Saint-Malo	France
23	ICANS	Strasbourg	France
24	Gustave Roussy	Villejuif	France