Comparing short-course radiotherapy and long-course chemoradiation for preserving organs in low rectal cancer

A Multicenter, Open, Randomized, Phase II Trial：Short-course Radiotherapy or Long-course Chemoradiation Followed by MFOLFOXIRI Consolidation Chemotherapy for Organ Preservation in Low Rectal Cancer

This study is testing whether short-course radiotherapy or long-course chemoradiation is better at helping people with low rectal cancer keep their organs and avoid major surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06417476 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of two neoadjuvant therapy approaches—short-course radiotherapy and long-course chemoradiation—followed by consolidation chemotherapy with mFOLFOXIRI in patients with low rectal cancer. The trial is randomized and open-label, involving patients aged 18 to 70 with clinical stage II-III locally advanced rectal cancer from multiple centers in China. The primary goal is to assess the one-year organ preservation rate and compare it to historical data, while also exploring biomarkers that may predict tumor response. Patients will undergo a series of treatments and evaluations to determine the best approach for minimizing the need for radical surgery.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with locally advanced rectal adenocarcinoma located within 8 cm of the anus and specific clinical staging.

Not a fit: Patients with distant metastasis or those with tumors not meeting the specified criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve organ preservation rates and quality of life for patients with low rectal cancer.

How similar studies have performed: Other studies have shown promise with similar neoadjuvant approaches, but this specific combination is being explored for the first time in this context.

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.

Where this trial is running

Guangzhou, Guangdong

• 651 Dongfeng Road East — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Peirong Ding, MD, Ph D

Conditions: Rectal Neoplasms, Neoadjuvant chemotherapy, Preoperative radiotherapy, Chemoradiotherapy, Consolidation chemotherapy, mFOLFOXIRI