ADAGE – PRODIGE 34

The elderly population of the study will be divided into 2 groups according to the choice of the investigator, after a multidisciplinary evaluation involving geriatric parameters, with two
independent randomisations.

Primary objectives: To compare the disease-free survival (DFS) of 2 therapeutic strategies in each group of patients aged 70 years or older over a period of 3 years, after resection of a stage III colon or upper rectal cancer.
Group 1 (able to receive bi-chemotherapy): A 7 % improvement in DFS is expected in the
oxaliplatin arm compared to the arm with 5FU or capecitabine.
Group 2 (unable to receive bi-chemotherapy): A 15 % improvement in DFS is expected in
the chemotherapy arm (5FU or capecitabine) compared to the arm with observation only.
Secundary objectives:
Dose intensity, tolerance (NCI CTC 4.0), time to recurrence, overall survival, time until
degradation of autonomy, time until deterioration of the quality of life.
Exploratory evaluation: research for prognostic factors derived from geriatric evaluation, evaluated according to the primary endpoint.

• Age ≥ 70 years
• Patient deemed fit to receive chemotherapy by the multidisciplinary consultation meeting (MCM)
• Detailed Lee score, faxed to the randomisation center
• stage III adenocarcinoma of the colon or upper rectum
• R0 Resection of the primary tumor
• Possibility to start adjuvant chemotherapy within 12 weeks after surgery
• Absence of previous chemotherapy for colon cancer
• Geriatric Self-Questionnaire "Patient" completed, faxed to the randomisation center
• Geriatric “team” questionnaire completed, faxed to the randomisation center
• Effective contraception for male patients, throughout the treatment and at least 6 months after discontinuation of oxaliplatin
• Signed informed consent (s)

• Other progressive malignant tumor (cancer not stabilized for less than 2 years)
• Rectal cancer (located less than 15 cm from the anal margin by endoscopy or subperitoneal)
• Neutrophils <2,000 / mm3 for group 1 and Neutrophils <1,500 / mm3 for group 2 and platelets <100,000 / mm3 or hemoglobin <9 g / dL
• Neuropathy for Group 1 patients.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Patient with severe hepatic insufficiency.
• Any contraindications to the drugs used in the study (refer to the updated versions of the SPCs of the products used, in Annex 10).
• Not able to undergo the trial medical follow-up for geographical, social or psychological reasons.

• Group 1: Patients deemed fit to receive dual chemotherapy by the multidisciplinary consultation meeting (MCM):
  • Arm A: fluoropyrimidine monotherapy (simplified LV5FU2 or capecitabine); 12 cycles of LV5FU2 or 8 cycles of capecitabine
  • Arm B: Simplified FOLFOX 4 (or XELOX); 12 cycles of FOLFOX or 8 cycles of XELOX
• Group 2: Patients found to be unsuitable for bi-chemotherapy by the MCM.
  • Arm C: observation
  • Arm D: fluoropyrimidine monotherapy (simplified LV5FU2 or capecitabine); 12 cycles of LV5FU2 or 8 capecitabine

Choice of chemotherapy: The schedules using capecitabine or oxaliplatin are not
recommended if the creatinine clearance, calculated according to Cockcroft and Gault, is
<30 mL / min. In this case, the patient cannot be included in group 1; he can only be
included in group 2 if he receives 5FU infusion.
We recommend that patients with a history of heart disease will not be treated with
capecitabine. Attention: in case of use of this product in these patients, it will be necessary
to perform an ECG at Tmax, approximately 1.5h after the first capecitabine intake.

Recruitment Start Date (FPI): 2019
Recruitment Finish Date (LPI): 2022
Follow-up Period End Date (LPO): 2028 (5 year follow-up)
End of trial is defined by the last patient last visit

Prof Marc Van den Eynde

FFCD

UCL St-Luc
ULB Hôpital ERASME
CHU-UCL - Site Sainte Elisabeth
CHC St Joseph
CHU AMBROISE PARE
Onze Lieve Vrouw Ziekenhuis Aalst
CHU-UCL - Site Godinne