Comparing two treatment approaches for locally advanced rectal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This multicenter randomized Phase III trial aims to determine whether a combination of short-course preoperative radiation and a triplet chemotherapy regimen (CAPOXIRI) is superior to a doublet regimen (CAPOX) for patients with locally advanced rectal cancer. The study will assess the effectiveness of total neoadjuvant therapy (TNT) in achieving complete clinical responses, potentially allowing some patients to avoid radical surgery. Participants will be re-staged after treatment to evaluate their response and will be monitored for up to five years through various imaging and biopsy methods.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. The content of this research was fully explained, and written informed consent was obtained from the subject.
2. Histologically confirmed rectal adenocarcinoma.
3. Radical resection is clinically possible without any distant metastases on imaging studies.
4. Age of 18 years or older on the date of consent acquisition.
5. Eastern Cooperative Oncology Group (ECOG) PS 0-1 (PS 0 if aged 70 years or older on consent acquisition date).
6. Inferior margin of the tumor is within 12 cm of the AV.
7. No prior tumor treatment.
8. No history of radiation therapy to the pelvis, including treatment for other cancer types.
9. Cases with cT3-4N0M0\*or T1-4N1-2M0 based on Union Internationale Contre le Cancer (UICC) 8th edition.

   (\*5 cm\< AV ≤ 10 cm, T3a/bN0M0, extramural venous invasion (EMVI) -, mesorectal fascia (MRF) clear and 10 cm \< AV ≤ 12 cm, T3a/bN0-1M0, EMVI-, MRF clear are eligible only for those who refused surgery)
10. UGT1A1 is wild-type or single heterozygous.
11. Criteria for major organ function within 28 days prior to enrollment. If there are multiple test results within this period, the most recent one will be used, and blood transfusions and hematopoietic factor preparations will not be administered within 14 days before the test date for measurements before registration.

    1. Neutrophil count: ≥1,500/mm3
    2. Platelet count: ≥10.0×10 4/mm3
    3. Hemoglobin concentration: ≥9.0 g/dL
    4. Total bilirubin: ≤2.0 mg/dL
    5. Aspartate transaminase (AST): ≤100 IU/L or less
    6. Alanine transaminase (ALT): ≤100 IU/L or less
    7. Serum creatinine: Creatinine clearance ≥30 mL/min (by Cockcroft \& Gault formula)

Exclusion Criteria:

1. Extensive surgery (excluding colostomy and central venous port construction) within 4 weeks before starting protocol treatment.
2. Complications or history of severe lung disease (such as interstitial pneumonia, pulmonary fibrosis, and severe emphysema).
3. Colonic stent in place.
4. Contraindications for MRI such as cardiac pacemakers.
5. Serious comorbidities (such as heart failure, renal failure, liver failure, intestinal paralysis, intestinal obstruction, uncontrolled diabetes, and active inflammatory bowel disease).
6. Patients with multiple active cancers (simultaneous multiple cancers or metachronous multiple cancers with a disease-free interval of 5 years or less). However, carcinoma in situ or lesions equivalent to intramucosal carcinoma, which can be cured by local treatment, are not treated as active multiple cancers.
7. Pregnant women, lactating women, positive pregnancy test, or unwillingness to use contraception.
8. Hepatitis B surface (HBs) antigen positive or hepatitis C virus (HCV) antibody-positive. However, HCV-RNA-negative can be registered.
9. Have human immunodeficiency virus (HIV) infection.
10. MSI-high (MSI-H) or defective mismatch repair (dMMR) is known.
11. Unwilling to donate specimens for "Research on gene profiling and clinical significance using clinical specimens from cancer patients" for whole-genome analysis based on the "Action Plan for Whole-Genome Analysis, etc." (CONDUCTOR study).
12. Any other patients the principal investigator or co-investigator deems inappropriate for study participation.

Where it's running

• National Cancer Center Hospital East
  Chiba, Japan Recruiting
• Ehime Prefectural Central Hospital
  Ehime, Japan Recruiting
• Kyushu University Hospital
  Fukuoka, Japan Recruiting
• National Hospital Organization Kyushu Cancer Center
  Fukuoka, Japan Recruiting
• National Hospital Organization Kyushu Medical Center
  Fukuoka, Japan Recruiting
• Gifu University Hospital
  Gifu, Japan Recruiting

Study contacts

• Study coordinator: Yoshinori Kagawa, MD., PhD
• Email: yoshinori.kagawa@oici.jp
• Phone: +81-6-6945-1181

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Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.