TARGETed Therapy Drug MONITOring in DIGestive Oncology

Not Applicable

Recruiting

• Conditions: Digestive Cancer; GIST; Hepatocellular Carcinoma; Metastatic Colorectal Cancer; Neuroendocrine Tumors
• Interventions: Other: Blood sampling to build population pharmacokinetics model

• Registration Number: NCT05443087
• Lead Sponsor: UNICANCER

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.

Detailed Description

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 Timeline

• Study First Submitted: 2022-06-23
• Study First Submitted QC: 2022-07-01
• Study First Posted: 2022-07-05
• Study Start: 2022-08-29
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Primary Completion: 2026-08
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 330

Inclusion Criteria

1. Patient aged 18 years or over

2. 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

3. Life expectancy of greater than 3 months - at the discretion of the investigator

4. Measurable disease according to tumor evaluation criteria as per local practice (Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, etc.)

5. Patients must be affiliated to a Social Security System (or equivalent)

6. 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

1. Other concomitant anticancer systemic treatment (chronic chemotherapy, antitumor hormone therapy or immunotherapy) than the one studied
2. Unresolved toxicity higher than NCI-CTCAE v5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia and peripheral neuropathy
3. 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.
4. 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
5. 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.
6. 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
7. 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)
8. Patient deprived of their liberty or under protective custody or guardianship

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (29)

CH d'Auxerre; 🇫🇷 Auxerre, France

Hôpital Beaujon APHP; 🇫🇷 Clichy, France

Institut Jean Godinot; 🇫🇷 Reims, France

CHU Rouen - Hôpital Charles Nicolle; 🇫🇷 Rouen, France

CHU d'Amiens Pcardie - Hopital Sud; 🇫🇷 Amiens, France

CH de Bayeux - Onconormandie; 🇫🇷 Bayeux, France

Centre Jean Perrin; 🇫🇷 Clermont-Ferrand, France

Institut du Cancer Avignon - Institut Sainte Catherine; 🇫🇷 Avignon, France

Centre Georges Francois Leclerc; 🇫🇷 Dijon, France

Institut de Cancérologie de Bourgogne; 🇫🇷 Dijon, France

Centre Oscar Lambret; 🇫🇷 Lille, France

Centre Léon Bérard; 🇫🇷 Lyon, France

Hôpital Européen Marseille; 🇫🇷 Marseille, France

CHRU de Nancy - Hôpital de Brabois Adulte; 🇫🇷 Nancy, France

Groupement des hôpitaux de l'Institut Catholique de Lille - Hôpital Saint Vincent de Paul; 🇫🇷 Lille, France

CHU de Nantes - Hôtel Dieu; 🇫🇷 Nantes, France

Institut Mutualiste de Montsouris; 🇫🇷 Paris, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Hôpital Saint Joseph; 🇫🇷 Paris, France

APHP Pitié Salpétrière; 🇫🇷 Paris, France

CHU de Reims - Hôpital Robert Debré; 🇫🇷 Reims, France

Hôpital Privé des Côtes d'Armor - SAS; 🇫🇷 Plérin, France

CHU de Poitiers; 🇫🇷 Poitiers, France

Centre Eugène Marquis; 🇫🇷 Rennes, France

ICANS; 🇫🇷 Strasbourg, France

CHU de Tours; 🇫🇷 Tours, France

CH Saint Malo - Hôpital Broussais; 🇫🇷 Saint-Malo, France

CH Eure Seine - Hopital d'Evreux Vernon; 🇫🇷 Évreux, France

Gustave Roussy; 🇫🇷 Villejuif, France