Personnaliser et affiner la chimiothérapie néo-adjuvante dans le cancer du côlon localement avancé mais résécable chez le sujet âgé de 70 ans ou plus

Essai clinique

Type : Académique
Statut : Ouvert
Phase : III
Étape du traitement : Traitements combinés
Date d'ouverture : 21/02/2023
Date clôture : 31/12/2025
Promoteur : Intergroupe Study FFCD – UNICANCER GI - GERCOR
Progression du cancer: Loco-régional
Résumé :

Arm A (experimental arm): NAC arm, patients will receive FOLFOX (folinic acid, fluorouracil and oxaliplatin) for 6 weeks (3 courses) before surgery.
The treatment consists of the administration of:
-Folinic acid by intravenous infusion: 400 mg/m² (or 200 mg/m² if Elvorine) during 2 hours
-Oxaliplatin by intravenous infusion: 85 mg/m² in G5 % 500 ml during 2 hours
-5 FU: 400 mg/m² IV bolus injection over 5 minutes
5 - FU continuous by intravenous infusion: 2400 mg/m² in NaCl 0,9 % in IV during 46 hours
Courses will be repeated every 2 weeks until 6 weeks or unacceptable toxicity and surgery will be performed between 2 and 4 weeks from last dose of NAC.
Arm B (control arm): patients will receive the current standard of care: upfront surgery (STS) as soon as possible

Domaines/spécialités :
  • Cancers digestifs
    • Colon
Pathologies :
  • Tumeur maligne du côlon - Cim10 : C18

Critères de population

Sexe : Homme et femme
Age minimum : 70 ans
Critères d’inclusion :

Biopsy-confirmed adenocarcinoma of the colon (or upper rectum if too high for radiotherapy), high-grade dysplasia is acceptable with unequivocal radiological

evidence of invasive cancer (Patients with synchronous tumors are eligible, if the most advanced tumor meets the criteria above)
- Radiological stage T3/T4 and N0/N1/N2 and M0
- Patient eligible for curative surgery (without the necessity of chemotherapy)
- No clinical or radiological evidence of bowel obstruction
- Age ≥ 70 at the time of registration
- Patient able and willing to provide written informed consent for the study
- pMMR/MSS tumour status
- Colon cancer specialist assessing fitness for patient to receive 6 weeks (3 courses) of NAC with FOLFOX (either full or 80% of FOLFOX dose) and surgery
- homozygous for DPYD germline mutations (uracilemia <16 ng/ml)
- Adequate full blood count: WBC >3.0 x109/l; platelets >100 x109/l and neutrophils ≥ 1.5 x x109/l Anaemia (Hb < 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given according to the decision of the surgical and oncology teams.
- Adequate renal biochemistry: GFR >50 ml/min as assessed by local standards
- Adequate hepatobiliary function:
o bilirubin < 1.5 ULN (Patients with Gilbert’s syndrome who have raised bilirubin but otherwise normal liver function tests are eligible for the study if bilirubin < 3 ULN)
o AST/ALT < 2.5 x ULN
- If female, and of childbearing potential, she must agree to avoid pregnancy during and for 6 months after last dose of study treatment*
- If male with a partner of childbearing potential, he must:
o Agree to use adequate, medically approved, contraceptive precautions during and for 6 months after the last dose of study treatment*
- Ability of the patient to understand, sign and date the informed consent before randomisation
- Signed the Informed Consent form for randomisation
- Patient affiliated to a social security scheme

Critères d’exclusion :

Any patient for whom radiotherapy is advised by the MDT
- Strong evidence of distant metastases or peritoneal nodules (cM1), However, cases with indeterminate abnormalities should be managed and investigated as per standard local MDT procedures and can be considered for trial entry if the MDT opinion is that these are considered most likely to be benign.
- Peritonitis (secondary to perforated tumour)
- T1-T2
- Serious medical comorbidity, as assessed by leading clinician (such as uncontrolled angina)
- Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <10%
- Known dMMR/ MSI-H tumour status
- Have a peripheral sensitive neuropathy with functional impairment (≥ grade 2 according to NCI-CTCAE v5.0)
- Recent (within four weeks prior to randomisation) or concomitant treatment with brivudine, sorivudine or their chemically related analogues
- Person under guardianship, curatorship, and safeguard of justice or person deprived of liberty
- Impossible to undergo the medical follow-up of the trial for geographical, social or psychological reasons
- Hypersensitivity to the active substance of the trial treatments or to any of the excipients
- Pregnant or breastfeeding woman

- Patient with poor nutritional status at appreciation by each clinician
- bone marrow hypoplasia
- Potentially severe infection 1 month before NAC
- Patients who have received live attenuated vaccines (yellow fever, varicella, shingles, measles, mumps, rubella, tuberculosis, rotavirus, influenza) 1 month before NAC
- Any chronic condition not balanced in the last 6 months: liver failure, renal failure, respiratory failure, heart failure
- QT/QTc interval > 450 msec for men and > 470 msec for women
- Known Pernicious anaemia or other anaemias due to vitamin B12 deficiency

Centre d'investigation

En cours
Nom : CH d'Auxerre
Ville : AUXERRE (89)
RESPONSABLE MÉDICAL
Aucun responsable médical renseigné
CONTACT TECHNIQUE
Nom : POREBSKI
Prénom : Cassandra
Téléphone : 03 86 48 44 67
Email : cporebski@ch-auxerre.fr

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