Neoadjuvant FOLFIRINOX and Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer Patients

Neoadjuvant FOLFIRINOX and Preoperative Chemoradiotherapy Versus Standard Total Neoadjuvant Approach for Locally Advanced Rectal Cancer Patients: a Randomized Controlled Phase 2 Trial.

A phase II clinical trial compared standard TNT (mFolfox6 and CRT) with preoperative chemoradiotherapy (CRT) with neoadjuvant chemotherapy (CT) containing mFolfirinox in patients with locally advanced rectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Rectum Cancer
• Intervention / Treatment: Drug: mFolfox6; Drug: mFOLFIRINOX

Detailed Description

This open-label randomized, two-arm phase II trial compared the standard total neoadjuvant approach (TNT) with neoadjuvant CT with mFolfirinox and preoperative CRT in patients with locally advanced rectal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: E Morkos; Phone Number: 00201061323285; Email: yoyonagy7@gmail.com

Study Locations

• Egypt
  • Menoufia
    • Shibīn Al Kawm, Menoufia, Egypt, 32511
      • Recruiting
      • Medicine
      • Contact: faculty of medicine; Phone Number: +20 0482330325; Email: medcine@menofia.edu.eg
      • Contact: Phone Number: +20 0482224819

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically proven rectal adenocarcinoma.
2. Stages cT3 with risk of local recurrence, cT4, or N positive, M0 and for which a multidisciplinary meeting recommend TNT.
3. Resectable tumor, or considered as potentially resectable after CRT.
4. No distant metastases.
5. Patient eligible for surgery
6. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0/1.
7. No heart failure or coronary heart disease symptoms (even controlled).
8. No peripheral neuropathy > grade 1.
9. No prior radiotherapy of the pelvis for any reason and no previous CT
10. No major comorbidity that may preclude the delivery of treatment
11. Adequate contraception in fertile patients.
12. Adequate hematologic function.

13 Adequate hepatic function.

14. Signed written informed consent.

Exclusion Criteria:

1. Metastatic disease
2. Unresectable rectal cancer, including prostatic involvement or extension to pelvic floor muscles Contraindication to 5-FU, or to oxaliplatin or to irinotecan, including Gilbert disease or genotype UGT1A1
3. Medical history of chronic diarrhea or inflammatory disease of the colon or rectum
4. Medical history of angina pectoris or myocardial infarction
5. Other concomitant cancer.
6. Pregnant or breast-feeding woman.
7. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (mFolfox6); Chemotherapy (mFolfox6) then radiochemotherapy	Drug: mFolfox6; Neoadjuvant chemotherapy
Experimental: Arm B (mFOLFIRINOX); Chemotherapy (mFOLFIRINOX) then radiochemotherapy	Drug: mFOLFIRINOX; Neoadjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete clinical response rate	an absence of clinical, endoscopic or imaging evidence of a rectal tumor during the restaging of a patient with locally advanced rectal cancer after neoadjuvant therapy.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity of chemotherapy	Common Terminology Criteria for Adverse Events (CTCAE) v 5	6 months
complete pathological response rectal cancer	the absence of malignant cells on the specimen of rectal resection in patients who were previously treated with neoadjuvant CRT.	6 months
disease-free survival	Disease-free survival (DFS) will be defined as the time from randomization to recurrence of tumor or death	3 years
Overall survival	Overall survival will be defined as the time from randomisation to the time of occurrence of the first death regardless to its cause. Patients alive at the time of analysis will be censored at the date of the last follow up.	5 years

Collaborators and Investigators

• Sponsor: Menoufia University
• Investigators: Principal Investigator: Yostena Mekhail, MD,PhD, Menoufia University

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2025
• Primary Completion (Estimated): January 25, 2027
• Study Completion (Estimated): February 25, 2027

Study Registration Dates

• First Submitted: February 1, 2025
• First Submitted That Met QC Criteria: February 1, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 15, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Neoadjuvant; mFOLFIRINOX; TNT; Complete clinical response; Watch and wait approach; Sphincter sparing
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: R2025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No