Short-course Radiotherapy or Long-course Chemoradiation Followed by mFOLFOXIRI Consolidation Chemotherapy for Organ Preservation in Low Rectal Cancer

NCT06417476 | Active Not Recruiting Phase 2

• 1 other identifier: B2022-714
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Given the growing focus on preserving organ function and the utilization of neoadjuvant therapy, it is important to investigate and enhance the application of comprehensive neoadjuvant therapy in low rectal cancer. This approach aims to minimize or circumvent the organ dysfunction and subsequent decline in quality of life associated with radical surgery, with improving disease-free survival (DFS), while . Consequently, we propose to initiate a multicenter clinical trial to examine the medium- and long-term effectiveness of complete neoadjuvant therapy (comprising either short-course radiotherapy or long-course chemoradiation, followed by consolidation chemotherapy with mFOLFOXIRI) in increasing organ preservation rates in patients with low rectal cancer.

Conditions

Rectal Neoplasms

Keywords

Neoadjuvant chemotherapy; Preoperative radiotherapy; Chemoradiotherapy; Consolidation chemotherapy; mFOLFOXIRI

Outcome Measures

Primary Outcomes (1)

• Organ preservation rate

  The 1-year organ preservation rate is the percentage of patients attaining a complete clinical response (cCR) or near-complete clinical response (near-cCR) following neoadjuvant therapy, who then proceeded with non-surgical management or local excision, was monitored under a Watch \& Wait strategy or for 1 year post-local resection without undergoing radical surgery.

  Up to 1 years

Secondary Outcomes (10)

• Clinical complete response

  Up to 24 weeks

• Pathological complete response

  Up to 24 weeks

• Near clinical complete response

  Up to 24 weeks

• Disease free survival

  Up to 3 years

• Overall survival

  Up to 3 years

Study Arms (2)

Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI

EXPERIMENTAL

Patients receive short-course radiotherapy (25Gy/5 times) followed by consolidation chemotherapy with mFOLFOXIRI (Irinotecan 150 mg/m2 iv gtt (2h) d1, Oxaliplatin 85 mg/m2 iv gtt (2h) d1, Calcium folinate 400 mg/m2 iv gtt (2h) d1, Total amount of fluorouracil 2400 mg/m2 iv gtt (48h)), treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. The first efficacy evaluation occurs after the fourth chemotherapy cycle. If there is no progression (a complete response (CR), partial response (PR), or stable disease (SD) with reduction or stability in tumor size) , patients will proceed with an additional four cycles. Upon the final efficacy assessment after the eighth chemotherapy cycle, patients will received several pathways (watch \& wait approach; local resection;total mesorectal excision) are considered based on the assessments.

Radiation: Short-course radiotherapy; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Calcium Formate; Drug: Fluorouracil

Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI

EXPERIMENTAL

Patients receive long-course chemoradiation (50Gy/25 times;capecitabine 825 mg/m² twice daily) followed by consolidation chemotherapy with mFOLFOXIRI (Irinotecan 150 mg/m2 iv gtt (2h) d1, Oxaliplatin 85 mg/m2 iv gtt (2h) d1, Calcium folinate 400 mg/m2 iv gtt (2h) d1, Total amount of fluorouracil 2400 mg/m2 iv gtt (48h)), treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. The first efficacy evaluation occurs after the fourth chemotherapy cycle. If there is no progression (a complete response (CR), partial response (PR), or stable disease (SD) with reduction or stability in tumor size) , patients will proceed with an additional four cycles. Upon the final efficacy assessment after the eighth chemotherapy cycle, patients will received several pathways (watch \& wait approach; local resection;total mesorectal excision) are considered based on the assessments.

Drug: Irinotecan; Drug: Oxaliplatin; Drug: Calcium Formate; Drug: Fluorouracil; Radiation: Long-course chemoradiation; Drug: Capecitabine

Interventions

Short-course radiotherapy RADIATION

The total dosage was 25Gy consisted of 5 fractions of 5 Gy to clinical target volume without a boost dose

Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI

Irinotecan DRUG

150 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.

Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI; Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI

Oxaliplatin DRUG

85 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.

Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI; Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI

Calcium Formate DRUG

400 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.

Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI; Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI

Fluorouracil DRUG

2400 mg/m² iv drip over 48 hours on day 1-2, repeated every 14 days.

Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI; Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI

Long-course chemoradiation RADIATION

The total dosage was 50Gy consisted of 25 fractions of 2 Gy to clinical target volume without a boost dose

Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI

Capecitabine DRUG

825 mg/m² twice daily administered orally and concurrently with radiation therapy for 5 days per week.

Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis: Histologically confirmed rectal adenocarcinoma. Preoperative Staging: Clinical stages cT2-4aN0-2. Tumor Location: Tumor's lower edge within 8cm from the anus, potentially affecting anal preservation or function.
• Metastasis Screening: Preoperative chest, abdomen, and pelvis CT to rule out distant metastasis.
• Biomarkers: Positive expression of pMMR (MSH1/MSH2/MSH6/PMS2) on tumor biopsy immunohistochemistry.
• Staging Methods: Combination of thoracic and abdominal pelvic CT, pelvic MRI, and endoscopic or transrectal ultrasound.
• Patient Characteristics Age: 18 to 70 years. Performance Status: ECOG score of 0-1. Life Expectancy: At least 2 years. Blood Counts: WBC \>4000/mm\^3, PLT \>100,000/mm\^3, Hb \>10g/dL (chronic anemia with Hb \< 10.0g/dL subject to multidisciplinary team review).
• Liver Function: Serum total bilirubin ≤1.5×ULN (≤3×ULN for Gilbert syndrome); AST and ALT ≤2.5×ULN.
• Renal Function: Serum creatinine ≤1.5×ULN or creatinine clearance \>50 mL/min. Other Criteria: Non-pregnant, not nursing, no other malignancies (except non-melanoma skin cancer or cervical carcinoma in situ) within the past 5 years, capable of providing informed consent, no severe comorbidities affecting survival.
• Prior Treatment No prior surgery, chemotherapy, or radiotherapy for rectal cancer. No prior biological therapy. No restrictions on previous endocrine therapy.

You may not qualify if:

• Informed Consent: Lack of signed informed consent. Genetic Markers: Tumor biopsy indicating dMMR or MSI-H detected. Advanced Tumor Stage: Preoperative assessment showing tumor invasion of surrounding tissues/organs (T4b).
• Obstruction: Unresolved colonic obstruction; presence of tumor perforation. Metastasis: Evidence of preoperative distant metastasis. Cardiac Conditions: Arrhythmia requiring antiarrhythmic therapy (excluding beta-blockers or digoxin), symptomatic coronary artery disease or recent myocardial ischemia (within 6 months), or congestive heart failure above NYHA Grade II.
• Hypertension: Severe, poorly controlled hypertension. Infections: HIV infection, active chronic hepatitis B or C, other serious infections; active tuberculosis or anti-TB therapy within the past year.
• Organ Function: Poor fluid quality, organ function decompensation. Previous Treatment: History of pelvic or abdominal radiotherapy; multiple primary colorectal cancers.
• Neurological Conditions: Seizures requiring management (e.g., steroids, antiepileptic therapy).
• Cancer History: Other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ or basal cell carcinoma of the skin.
• Substance Abuse: Substance abuse or medical, psychological, or social conditions affecting study participation or result evaluation.
• Allergies: Known or suspected allergy to study drugs or related medications. Stability: Any unstable condition that may compromise safety or compliance. Reproductive Status: Pregnant or lactating women, or fertile women not using effective contraception.

Sponsors & Collaborators

• Pei-Rong Ding: lead
• Yunnan Cancer Hospital: collaborator
• Liaoning Cancer Hospital & Institute: collaborator
• Shantou Central Hospital: collaborator
• Fujian Cancer Hospital: collaborator
• Jiangsu Provincial People's Hospital: collaborator

Study Sites (1)

651 Dongfeng Road East

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Irinotecan; Oxaliplatin; formic acid; Fluorouracil; Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Peirong Ding, MD, Ph D

  Sun Yat-sen University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: February 4, 2024
• First Posted: May 16, 2024
• Study Start: December 12, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): December 30, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CN (1)