Study Evaluating the Tailored Management of Locally-advanced Rectal Carcinoma

• Status: Not yet recruiting
• Trial end date: 2027-08-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Treatments: Folfirinox

Criteria

Inclusion Criteria:

1. Written consent for study,

2. Patients aged over 18 years old,

3. WHO performance status 0-1,

4. Histologically confirmed diagnosis of adenocarcinoma of the rectum,

5. Distal part of the tumor from 2 to 12 cm from the anal verge,

6. No unequivocal evidence on CT-Scan of established metastatic disease,

7. MRI evaluation of the locally advanced tumor:

1. Predictive CRM < 2mm

2. T3c-d (extending ≥ 5mm beyond the muscularis propria) with EMVI (extra mural venous invasion)

3. T4a - b (except bone and sphincteric invasion),

8. General condition considered suitable for radical pelvic surgery and a systemic therapy with FOLFIRINOX,

9. Adequate hematologic, hepatic, renal and ionogram function assessed within 7 days prior to study treatment

1. Platelet count ≥ 100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3

2. Total bilirubin ≤ 1.5 x ULN, Alkaline phosphatases ≤ 3 x ULN and AST and ALT

≤ 3 x ULN

3. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min according to MDRD,

4. Kalemia, Calcemia and Magnesemia within normal limits,

10. 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),

11. 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,

12. No evidence of chronic or acute ischemic heart disease,

13. Willing to participate to the study, and able to give informed consent and to comply with the treatment and follow-up schedules,

14. Affiliation to the French Social Security System.

After neoadjuvant chemotherapy, the patient must also meet the following criteria

• Patient with tumoral regression ≥ 60% and CRM ≥ 1mm

Non-Inclusion criteria

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. Patient with a history of chemotherapy or pelvic radiotherapy

4. Contraindication to chemotherapy and/or radiotherapy

5. Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)

6. Peripheral neuropathy ≥ 2

7. ECG with a cQT interval higher than 450 ms for men and higher than 470 ms for women

8. Active cardiac disease including any of the following:

1. Congestive heart failure ≥ New York Heart Association (NYHA) class 2 (appendix 4),

2. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months),

3. Myocardial infarction less than 6 months before first dose of treatment,

4. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).

9. 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)].

10. 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,

11. Any infection that could jeopardize treatment administration

12. 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).

13. History of inflammatory bowel disease

14. Patients with a history of pulmonary fibrosis or interstitial pneumonia

15. Patients using antivitamin K (Coumadin, etc.), it's possible to substitute the antivitamin K treatment with low molecular weight heparins (LMWHs) before starting chemotherapy.

16. Known hypersensitivity to any of the study drugs, study drug classes, or any constituent of the products.

17. Patient who received live attenuated vaccine within 10 days of inclusion

18. 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.

19. Patient treated with an investigational drug within the last 30 days.

20. Patient under curatorship or guardianship or safeguard justice

21. Inability to submit to medical monitoring of the trial for geographical, social or psychological reasons.