RECRUITING Phase 2 / Phase 3 ClinicalTrials.gov

Study Evaluating the Tailored Management of Locally-advanced Rectal Carcinoma

Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle • ClinicalTrials.gov ID: NCT04749108

Registry updated: 2026-09-02

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Description

Locally advanced rectal carcinoma raise the issue of both the oncological control, local and general, and the therapeutic morbidity. Surgery alone can cure only one out of two patients, radiochemotherapy improves the local control but the metastatic risk remains about 30% with enhanced postoperative morbidity and poor functional results. The tumor response to preoperative treatment is the major prognostic factor which revealed the aggressiveness of the tumor. To this day, there are no biologic predictive markers for tumor response. The purpose of this trial is to tailor the management according to the early tumoral response after short and intensive induction chemotherapy. MRI volumetric tumor response will be used to distinguish between good responders and bad responders. "Very good" responders will be randomized to either immediate surgery or radiochemotherapy followed by surgery (Standard arm: Cap 50).

Interventions

Induction chemotherapy - modified FOLFIRINOX regimen (Drug)
An induction chemotherapy (6 cycles) combining irinotecan 180 mg/m2, oxaliplatin 85 mg/m2, elvorin 200 mg/m2 followed by a 46-hour continuous infusion 2,400 mg/m2) will be delivered every 15 days (D1=D15).
Early tumor response evaluation by MRI volumetry (Other)
Two weeks after the CT completion, the tumor volume will be measured by MRI with specific software which automatically borders the tumor so as to determine the early tumor response. A centralized reassessment of all MRI exams will be systematically performed by two radiologists of the coordinator center.
Radiochemotherapy Cap 50 (Radiation)
RCT Cap 50 will combine radiotherapy at a dose of 50 Gy by either conventional 3D or Intensity-Modulated RadioTherapy (IMRT) (2 Gy per fraction, 5 fractions per week during 5 weeks / 44 Gy in mini pelvis, and boost 6 Gy on reduced peritumoral volume) with concomitant oral capecitabine at 1600 mg/m2 per day delivered the days of radiotherapy treatment (2 daily intake).
Radical proctectomy with total mesorectal excision (Procedure)
The proctectomy can be performed by laparoscopic surgery or conventional laparotomy.

Eligibility criteria

INCLUSION CRITERIA FOR SCREENING 1. Written consent, 2. Patient who receive Folfirinox, 3. Patient aged over 18 years old, 4. World Health Organization (WHO) performance status ≥ 1, 5. Histologically confirmed diagnosis of adenocarcinoma of the rectum, 6. Distal part of the tumor from 1 to 12 cm from the upper part of the levator ani (dynamic rectal examination), 7. No unequivocal evidence on CT-Scan of established metastatic disease, 8. MRI evaluation of the locally advanced tumor before neoadjuvant chemotherapy: 1. Predictive CRM \< 2 mm 2. Or T3c-d (extending ≥ 5 mm beyond the muscularis propria) with extra mural venous invasion (EMVI) 3. Or T4a-b (except bone and sphincteric invasion). NON INCLUSION CRITERIA FOR SCREENING 1. Non measurable rectal tumor or not assessed by MRI before inclusion, 2. Ultra-low rectal tumor at diagnosis which imposes radiotherapy administration (inferior tumor pole less than 1 cm from the upper part of the levator ani). 3. Active cardiac disease including any of the following: a. Congestive heart failure ≥ New York Heart Association (NYHA) class 2 (appendix 4), b. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), c. Myocardial infarction less than 6 months before first dose of treatment, d. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted), 4. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors \[Ta (non invasive tumor), Tis (carcinoma in situ) and T1 (lamina propria invasion)\], 5. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment. INCLUSION CRITERIA FOR EXPERIMENTAL TREATMENT 1. WHO performance status 0-1, 2. Patient with tumoral regression ≥ 60% and CRM ≥ 1mm, 3. No unequivocal evidence on CT-Scan of established metastatic disease, 4. General condition considered suitable for radical pelvic surgery and a systemic therapy with Capecitabine 5. Adequate hematologic, hepatic, renal and ionogram function assessed within 7 days prior to study treatment a. Platelet count ≥ 100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3 b. Total bilirubin ≤ 1.5 x Upper Limit Normal (ULN), Alkaline phosphatases ≤ 3 x ULN and ASpartate aminoTransferase (AST) and ALanine aminoTransferase (ALT) ≤ 3 x ULN, c. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min according to Modification of Diet in Renal Disease (MDRD), 6. For women of reproductive potential, negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test obtained within 7 days before the start of study treatment. Women not of reproductive potential are female patients who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy), 7. For women of childbearing potential and men, agreement to use an adequate contraception for the duration of study participation and up to 6 months following completion of therapy. Females of childbearing potential who are sexually active with a non-sterilized male partner must use 2 methods, of effective contraception. The investigator or a designated associate is requested to advise the patient on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care, 8. No evidence of chronic or acute ischemic heart disease, 9. Willing to participate to the study, and able to give informed consent and to comply with the treatment and follow-up schedules, 10. Affiliation to the French Social Security System. NON-INCLUSION CRITERIA FOR EXPERIMENTAL TREATMENT 1. Patient with a history of pelvic radiotherapy, 2. Contraindication to chemotherapy and/or radiotherapy, 3. Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL), 4. Any infection that could jeopardize treatment administration, 5. Any other serious concomitant disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, heart, kidney, lung, metabolic, or psychiatric disorders), 6. History of inflammatory bowel disease, 7. Patients with a history of pulmonary fibrosis or interstitial pneumonia, 8. Patients using antivitamin K (Coumadin etc…) but it's possible to substitute the antivitamin K treatment with low molecular weight heparins (LMWHs) before starting chemotherapy, 9. Known hypersensitivity to Capecitabine drug, study drug classes, or any constituent of the products, 10. Patient who received live attenuated vaccine within 10 days of inclusion, 11. Pregnant or breastfeeding woman. If a patient is of childbearing age, she must have a negative pregnancy test (serum β-hCG) documented 72 hours prior to inclusion, 12. Patient treated with an investigational drug within the last 30 days, 13. Patient under curatorship or guardianship or safeguard justice, 14. Inability to submit to medical monitoring of the trial for geographical, social or psychological reasons.

Conditions

Locally Advanced Malignant Neoplasm Rectal Carcinoma

Locations

Institut Paoli Calmettes — Marseille, Bouches Du Rhône, France
Hôpital Nord de Marseille — Marseille, Bouches Du Rhône, France
Hôpital Européen de MARSEILLE — Marseille, Bouches-du-rhône, France
CHU Besançon — Besançon, Doubs, France
CHU de Bordeaux — Bordeaux, Gironde, France
Insitut Régional du Cancer de Montpellier — Montpellier, Hérault, France
CHU de Nancy — Vandœuvre-lès-Nancy, Lorraine, France
Centre Alexis Vautrin — Nancy, Meurthe Et Moselle, France
Centre Oscart Lambret — Lille, Nord, France
CHU Amiens — Amiens, Picardie, France
CHU Clermont-Ferrand — Clermont-Ferrand, Puy De Dôme, France
CH PAU — Pau, Pyrénées-atlantiques, France
CHU de Lyon — Lyon, Rhône, France
CH Annecy — Annecy, Savoie, France
CHU Rouen — Rouen, Seine-Maritime, France
Hôpital Bicêtre — Le Kremlin-Bicêtre, Val De Marne, France
Bordeaux Colorectal Institute — Bordeaux, France
Centre Georges-François Leclerc — Dijon, France
Chu Grenoble — Grenoble, France
Chu Lille — Lille, France
CAC Léon Bérard — Lyon, France
Hôpital La Timone — Marseille, France
Centre Antoine Lacassagne — Nice, France
CHU de Nîmes — Nîmes, France
Hôpital Saint-Louis — Paris, France
Hôpital Saint-Antoine — Paris, France
Hôpital Européen Georges-Pompidou — Paris, France
Hôpital Diaconesses — Paris, France
Institut de Cancérologie de l'Ouest — Saint-Herblain, France
CHU de Toulouse — Toulouse, France

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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