Home › Trials › NCT04749108

Tailored management for locally advanced rectal cancer

Multicentric Phase II-III Study Evaluating the Tailored Management of Locally-advanced Rectal Carcinoma After a Favorable Response to Induction Chemotherapy

Phase2; Phase3 Interventional Institut du Cancer de Montpellier - Val d'Aurelle · NCT04749108

This study is testing a personalized treatment plan for people with locally advanced rectal cancer to see if early responses to chemotherapy can help decide whether they should have surgery right away or combine it with radiation therapy.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment1075 (estimated)
Ages18 Years and up
SexAll
SponsorInstitut du Cancer de Montpellier - Val d'Aurelle Academic / other
Drugs / interventionschemotherapy, radiation
Locations30 sites (Marseille, Bouches Du Rhône and 29 other locations)
Trial IDNCT04749108 on ClinicalTrials.gov

What this trial studies

This trial evaluates a personalized approach to managing locally advanced rectal carcinoma by assessing early tumor response to induction chemotherapy using MRI volumetric analysis. Patients identified as 'very good' responders will be randomized to receive either immediate surgery or radiochemotherapy followed by surgery. The goal is to improve treatment outcomes while minimizing unnecessary toxicity from standard neoadjuvant therapies. This approach aims to differentiate between good and poor responders to optimize treatment strategies.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with histologically confirmed adenocarcinoma of the rectum and specific tumor characteristics as assessed by MRI.

Not a fit: Patients with non-measurable tumors or those requiring immediate radiotherapy due to tumor location may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could lead to more effective and less toxic treatment options for patients with locally advanced rectal cancer.

How similar studies have performed: Other studies have shown promise in tailoring treatment based on early tumor response, indicating potential for success with this novel approach.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Marseille, Bouches Du Rhône and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Locally Advanced Malignant NeoplasmRectal Carcinoma
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.