Non Inferiority Study of Preoperative Chemotherapy Without Pelvic Irradiation for Rectal Cancer

• Status: Recruiting
• Trial end date: 2024-06-05
• Target enrollment: 0
• Participant gender: All

Summary

This study is a non-inferiority phase III randomised trial comparing preoperative chemotherapy alone (modified FOLFIRINOX) to chemotherapy followed by chemoradiotherapy in patients with primary resectable locally advanced rectal cancer. The primary endpoint of the study is 3-year progression free survival.

Expected 3 year PFS rate in the preoperative chemotherapy followed by chemoradiotherapy arm is 75%. This hazard rate, in an exponential survival model, corresponds to a decrease in the 3-year PFS rate on the preoperative chemotherapy arm to 67%. The study will randomize 540 patients (270 in the chemotherapy group and 270 in the chemoradiotherapy group) in 42 french academic centers.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Criteria

Inclusion Criteria:

• Histologically proven middle or low rectal carcinoma, ≤ 10 cm from the anal verge on MRI (sagittal slide)

• cT3N0 and/or cT1-T3N+ on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound),

• Pretreatment predictive circumferential margin > 2mm on pretreatment imaging work up (pelvic contrast enhanced MRI)

• Patients must be 18 years old or older

• A World Health Organization (WHO/ECOG) performance status of 0 or 1

• Informed consent signed

• Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

Exclusion Criteria:

• Rectal tumor > 10 cm from the anal verge on MRI (sagittal slide)

• cT4 tumor on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound) or involvement of external sphincter

• Circumferential margin ≤ 2 mm on pretreatment imaging work up (pelvic contrast enhanced MRI)

• Metastatic disease

• Prior pelvic irradiation or any contraindication to pelvic irradiation

• Contraindication to oxaliplatin or irinotecan or 5FU based chemotherapy

• Concomitant treatment with warfarin is contraindicated and warafarin must be replaced whenever possible to allow for inclusion.

• Recent or concomitant treatment with brivudine is contraindicated

• contraindications to 5-FU: complete and permanent insufficiency in dihydropyrimidine dehydrogenase, bone marrow insufficiency, chronic and severe infection

• contraindication to irinotecan : inflammatory bowel disease, bilirubin serum level > 3 times the upper limit of the normal rate, severe bone marrow insufficiency, WHO/ECOG performence status > 2,

• Concomitant treatment with millepertuis.

• contraindication to oxaliplatin :

*bone marrow insufficiency before treatment initiation (neutrophil count <2x109/L and/or platelet count <100x109/L), peripheral neuropathy with permanent invalidity before treatment initiation

• severe renal insufficiency (Creatinin clearance <30 ml/min)

• contraindications to folinic acid : Biermer anemia and other anemia related to B12 vitamin insufficiency

• contraindications to capecitabin : severe renal insufficiency (Creatinin clearance <30 ml/min), complete and permanent insufficiency in dihydropyrimidine dehydrogenase

• live attenuated vaccine should not be used during and 6 months after preoperative treatment.

• Previous colorectal cancer

• Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years

• Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

• protected adults

• Pregnancy or breastfeeding

• Patient with no national health or universal plan affiliation coverage.