TARGETed Therapy Drug MONITOring in DIGestive Oncology (TARGETMONITO)

March 25, 2025 updated by: UNICANCER

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

330

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Amiens, France
        • Recruiting
        • CHU d'Amiens Pcardie - Hopital Sud
        • Principal Investigator:
          • Vincent HAUTEFEUILLE
      • Auxerre, France
      • Avignon, France
        • Withdrawn
        • Institut du Cancer Avignon - Institut Sainte Catherine
      • Bayeux, France
        • Withdrawn
        • CH de Bayeux - Onconormandie
      • Clermont-Ferrand, France
      • Clichy, France
      • Dijon, France
        • Recruiting
        • Institut de Cancérologie de Bourgogne
        • Principal Investigator:
          • Véronique Lorgis
      • Dijon, France
        • Withdrawn
        • Centre Georges François Leclerc
      • Lille, France
      • Lille, France
        • Not yet recruiting
        • Groupement des hôpitaux de l'Institut Catholique de Lille - Hôpital Saint Vincent de Paul
        • Contact:
      • Lyon, France
        • Withdrawn
        • Centre léon bérard
      • Marseille, France
      • Nancy, France
        • Recruiting
        • CHRU de Nancy - Hôpital de Brabois Adulte
        • Contact:
      • Nantes, France
      • Nice, France
        • Withdrawn
        • Centre Antoine Lacassagne
      • Paris, France
      • Paris, France
      • Paris, France
        • Recruiting
        • Institut Mutualiste de Montsouris
        • Principal Investigator:
          • David MALKA
      • Plérin, France
        • Recruiting
        • Hôpital Privé des Côtes d'Armor - SAS
        • Contact:
      • Poitiers, France
      • Reims, France
        • Recruiting
        • CHU de Reims - Hôpital Robert Debré
        • Contact:
      • Reims, France
      • Rennes, France
      • Rouen, France
      • Saint-Malo, France
      • Strasbourg, France
      • Tours, France
        • Recruiting
        • CHU de Tours
        • Principal Investigator:
          • Romain CHAUTARD
      • Villejuif, France
      • Évreux, France
        • Not yet recruiting
        • CH Eure Seine - Hopital d'Evreux Vernon
        • Principal Investigator:
          • Bachar EL-SAYADI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Trough concentration (Ctrough)
Time Frame: 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.
From inclusion untill the end of treatment up to 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 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.
4 years
Overall survival
Time Frame: 4 years
Overall survival (OS) is the lenght of time between inclusion and death whatever the cause.
4 years
Objective response rate
Time Frame: 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).
4 years
Disease control rate
Time Frame: 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).
4 years
Safety: drug toxicity
Time Frame: 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.
Throughout study completion, up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNICANCER

Investigators

  • Principal Investigator: David MALKA, Dr, Gustave Roussy - Villejuif

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 29, 2022

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

June 23, 2022

First Submitted That Met QC Criteria

July 1, 2022

First Posted (Actual)

July 5, 2022

Study Record Updates

Last Update Posted (Actual)

March 30, 2025

Last Update Submitted That Met QC Criteria

March 25, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UC-GIG-2104
  • 2021-A01724-37 (Other Identifier: ID-RCB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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