COnCERTO

The aim of this study is to determine whether chemotherapy prior to tumor removal (neoadjuvant chemotherapy), in patients undergoing treatment for colon cancer in occlusion (CCO), would improve the rate of patients able to benefit from « optimal » treatment, i.e. complete treatment (including all neoadjuvant and adjuvant chemotherapy cures).

– Neoadjuvant chemotherapy Adverse events [ Time Frame: 36 months ]
– Adjuvant chemotherapy adverse events [ Time Frame: 36 months ]
– Number of cycles administered of neoadjuvant chemotherapy [ Time Frame: 36 months ]
– Rate of primary tumour resection [ Time Frame: 36 months ]
– Quality and completeness of the surgical excision [ Time Frame: 36 months ]
– Overall morbidity according to the Dindo classification [ Time Frame: at 90 days postoperatively. ]
– Overall mortality [ Time Frame: at 3 years and mortality without stoma at 3 years. ]
– Quality of life evaluated using EORTC QLQ-C30 and QLQ-CR29 dedicated to CRC [ Time Frame: at J0, week5 (FOLFOX)/week7 (CAPOX), week9 (FOLFOX) and every 6 months a year ]

No Intervention: Arm I (Adjuvant chemotherapy) / Control arm
Diverting stoma – colectomy – +/- adjuvant chemotherapy.
The colectomy (open or laparoscopic) should be performed within 1 to 20 days after the randomization and with respect of the oncological quality criteria of resection. After completion of surgery, adjuvant chemotherapy will be discussed as follow:
– Low-risk stage II: No adjuvant treatment
– High-risk MSS stage II (vascular emboli, lymphatic or perinervous invasion, poor differentiation, <12 harvested lymph nodes, perforation): Investigator’s discretion
– pT1-T3N1: CAPOX (3 months) or FOLFOX (6 months)
– pT4 and/or N2: FOLFOX (6 months)

Experimental: Arm II (Neoadjuvant Chemotherapy) / Experimental arm
Patients receive systemic CAPOX or FOLFOX chemotherapy (3 months) within 21 days after the randomization. After completion of neoadjuvant chemotherapy and within 3 to 5 weeks, the colectomy (open or laparoscopic) will be performed with respect of the oncological quality criteria. Adjuvant chemotherapy will be discussed as follow:
– Low-risk stage II: No adjuvant treatment
– High-risk MSS stage II (vascular emboli, perinervous or lymphatic invasion, poor differentiation, <12 harvested lymph nodes, perforation): Investigator’s discretion
– Stage III: CAPOX or FOLFOX (3 months)

1. Age ≥ 18 years.
2. ECOG performance status 0 or 1.
3. Patients with obstructive colon cancer treated by defunctioning stoma.
4. Pathologically confirmed adenocarcinoma (≥10 cm from the anal verge- left transverse colon) – MSS/pMMR (microsatellites stable primary tumor) status.
5. Patient requiring colectomy.
6. Laboratory data including : White blood cell count ≥ 3.10⁹/L with Neutrophils ≥ 1,5.10⁹/ L, Platelet count ≥ 100.10⁹/ L, Hemoglobin ≥ 9 g/dL (5,6 mmol/L), Total bilirubin ≤ 1,5 x ULN (upper limit of normal), ASAT and ALAT ≤ 2,5 x ULN, Alkaline phosphatase ≤ 1,5 x ULN, Serum creatinine ≤ 1,5 x ULN (performed 10-15 days prior to randomization).
7. Non metastatic colon cancer (lung, liver, peritoneal) on thoracic-abdomino-pelvis CT scan.
8. Absence of synchronous colorectal cancer, no suspicion of second colon cancer.
9. No prior chemotherapy or abdominal or pelvic irradiation.
10. No history of colorectal cancer.
11. No serious medical co-morbidity : uncontrolled inflammatory bowel disease, uncontrolled angina, recent [within the past 6 months] myocardial infarction, or another serious medical condition, judged to compromise ability to tolerate chemotherapy and/or surgery.
12. Women of childbearing potential with effective contraception will be required during chemotherapy treatment and for 15 months after cessation of chemotherapy treatment.
    1. for women of childbearing age effective contraception is required and a negative blood pregnancy test by beta-HCG at inclusion and and every month until the end of treatment
    2. for infertile women after oophorectomy or hysterectomy, the absence of the ovaries and/or uterus will be confirmed at inclusion
    3. for post-menopausal women, confirmation of the diagnosis is required (amenorrhea for at least 12 months prior to inclusion)
13. For men participating in the study, contraception is required during the trial and for 12 months after stopping chemotherapy treatment.
14. Patient able to comply with the study protocol, in the investigator’s judgment.
15. Patient affiliated with, or beneficiary of a social security (national health insurance) category.
16. Person informed and having signed his consent.

1. Contraindication to colectomy and/or anesthesia.
2. Rectal cancer located within 10 cm of the anal verge by endoscopy or under the peritoneal reflection at surgery.
3. Patient having received radiation therapy prior to surgery.
4. Metastatic spread at baseline assessment (lung, liver, peritoneal).
5. History or current evidence on physical examination of central nervous system disease or; Peripheral neuropathy ≥ grade 1.
6. Contraindication to study neoadjuvant chemotherapy treatments.
7. Presence of inflammatory bowel disease, HNPCC syndrome or polyposis.
8. Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia.
9. Uracilemia ≥ 150 ng/ml (suggestive of complete DPD deficiency).
10. Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent.
11. Any significant disease, which, in the investigator’s opinion, would exclude the patient from the study.
12. Patient is a pregnant (positive blood pregnancy test) or breastfeeding (lactating) woman or intending to become pregnant during the study and for at least 6 months after the treatment termination.
13. Person deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision).
14. Simultaneous participation in another interventional research.

Lancement de l’étude : Décembre 2024
Fin estimée des inclusions : Janvier 2032
Nombre de patients à inclure : 232

Pr Valérie BRIDOUX – CHU de Rouen

CHU de Rouen