Clinical trial NCT05443087: TARGETed Therapy Drug MONITOring in DIGestive Oncology
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Digestive Cancer
Metastatic Colorectal Cancer
Hepatocellular Carcinoma
GIST
Neuroendocrine Tumors
Keywords: multi kinases inhibitors
therapeutic drug monitoring
pharmacokinetics
pharmacodynamics
advanced digestive cancers
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2022-07-05
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Trough concentration (Ctrough)
timeFrame: From inclusion untill the end of treatment up to 4 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: 4 years
measure: Overall survival
timeFrame: 4 years
measure: Objective response rate
timeFrame: 4 years
measure: Disease control rate
timeFrame: 4 years
measure: Safety: drug toxicity
timeFrame: Throughout study completion, up to 4 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens Pcardie - Hopital Sud
city: Auxerre
country: France
facility: CH d'Auxerre
city: Avignon
country: France
facility: Institut du Cancer Avignon - Institut Sainte Catherine
city: Bayeux
country: France
facility: CH de Bayeux - Onconormandie
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Clichy
country: France
facility: Hôpital Beaujon APHP
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Dijon
country: France
facility: Institut de Cancérologie de Bourgogne
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Groupement des hôpitaux de l'Institut Catholique de Lille - Hôpital Saint Vincent de Paul
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital Européen Marseille
city: Nancy
country: France
facility: CHRU de Nancy - Hôpital de Brabois Adulte
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: APHP Pitié Salpétrière
city: Paris
country: France
facility: Hôpital Saint Joseph
city: Paris
country: France
facility: Institut Mutualiste de Montsouris
city: Plérin
country: France
facility: Hôpital Privé des Côtes d'Armor - SAS
city: Poitiers
country: France
facility: CHU de Poitiers
city: Reims
country: France
facility: CHU de Reims - Hôpital Robert Debré
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Rouen
country: France
facility: CHU Rouen - Hôpital Charles Nicolle
city: Saint-Malo
country: France
facility: CH Saint Malo - Hôpital Broussais
city: Strasbourg
country: France
facility: ICANS
city: Tours
country: France
facility: CHU de Tours
city: Villejuif
country: France
facility: Gustave Roussy
city: Évreux
country: France
facility: CH Eure Seine - Hopital d'Evreux Vernon
Study officials:
affiliation: Gustave ROUSSY - VILLEJUIF
name: David MALKA, Dr
role: PRINCIPAL_INVESTIGATOR
References: