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

NCT ID: NCT06417476

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-12
• Study Completion Date: 2025-12-31

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.

Detailed Description

This randomised, open-label, multicentre,phase II trial began in December, 2022, as a neoadjuvant trial about short-course radiotherapy or long-course chemoradiation followed by mFOLFOXIRI consolidation chemotherapy,in patients aged 18 years to 70 with clinical stage II-III locally advanced low rectal cancer from six Chinese institutions. The primary endpoint of the study was the 1-year organ preservation rate, with a comparison to historical data. Additionally, the study compared the differences between two radiotherapy regimens within the TNT treatment and explored biomarkers to predict tumor response

Patients with local advanced rectal cancer (cT2-4aN0-2,M0, 8cm from the anus verge) were recruited. Patients receive short-course radiotherapy (25Gy/5 times) followed by consolidation chemotherapy or long-course chemoradiation (50Gy/25 times;capecitabine 825 mg/m² twice daily) 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 8 courses in the absence of disease progression or unacceptable toxicity. The efficacy evaluation occurs after the fourth and eighth chemotherapy cycle. Patients showing a complete response (CR), partial response (PR), or stable disease (SD) with reduction or stability in tumor size are advised to continue and complete all planned consolidation chemotherapy. However, if the evaluation indicates stable disease with an increase (SD increased) or progressive disease (PD), and if an R0 resection (complete removal of the tumor with no cancer cells at the margins) is feasible, radical total mesorectal excision (TME) should be pursued. In cases where R0 resection is not achievable, the treatment should align with the guidelines for managing unresectable rectal cancer. Upon the final efficacy assessment after the eighth chemotherapy cycle, several pathways are considered based on the outcomes: patients achieving a clinical complete response (cCR) may proceed to a Watch & Wait approach. Those with a near clinical complete response (near cCR) undergo local transanal resection. If the patient's condition is evaluated as PR/SD with a reduction but does not qualify as near cCR, radical TME is recommended. For patients showing SD with an increase or PD, yet with a potential for R0 resection, radical TME is again the suggested course of action. If R0 resection is unattainable, treatment should adhere to the guidelines for unresectable rectal cancer.

Conditions

Rectal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI

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.

Group Type: EXPERIMENTAL

Short-course radiotherapy

Intervention Type: RADIATION

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

Irinotecan

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

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

Calcium Formate

Intervention Type: DRUG

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

Fluorouracil

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

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

Calcium Formate

Intervention Type: DRUG

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

Fluorouracil

Intervention Type: DRUG

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

Long-course chemoradiation

Intervention Type: RADIATION

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

Capecitabine

Intervention Type: DRUG

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

Interventions

Short-course radiotherapy

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

Intervention Type: RADIATION

Irinotecan

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

Intervention Type: DRUG

Oxaliplatin

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

Intervention Type: DRUG

Calcium Formate

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

Intervention Type: DRUG

Fluorouracil

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

Intervention Type: DRUG

Long-course chemoradiation

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

Intervention Type: RADIATION

Capecitabine

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pei-Rong Ding

OTHER

Sponsor Role: lead

Yunnan Cancer Hospital

OTHER

Sponsor Role: collaborator

Liaoning Cancer Hospital & Institute

OTHER

Sponsor Role: collaborator

Shantou Central Hospital

OTHER

Sponsor Role: collaborator

Fujian Cancer Hospital

OTHER_GOV

Sponsor Role: collaborator

Jiangsu Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Responsible Party

Pei-Rong Ding

Clinical Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Peirong Ding, MD, Ph D

Role: STUDY_CHAIR

Sun Yat-sen University

Locations

651 Dongfeng Road East

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Peirong Ding, MD, Ph D

Role: CONTACT

dingpr@sysucc.org.cn

13543478645 ext. +86

Kai Han, MD, Ph D

Role: CONTACT

hankai@sysucc.org.cn

18602042643 ext. +86

Facility Contacts

Peirong Ding, Doctor

Role: primary

dingpr@sysucc.org.cn

13543478645 ext. +86

Kai Han, Doctor

Role: backup

hankai@sysucc.org.cn

18602042643 ext. +86

Other Identifiers

B2022-714

Identifier Type: -

Identifier Source: org_study_id