Comparing two treatment approaches for locally advanced rectal cancer

A Multicenter Randomized Phase III Study of Short-term Radiotherapy Plus CAPOX and Short-term Radiotherapy Plus CAPOXIRI as Preoperative Treatment for Locally Advanced Rectal Cancer

This study is testing if a new combination of radiation and chemotherapy can help people with locally advanced rectal cancer respond better to treatment and possibly avoid major surgery.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 608 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: National Cancer Center Hospital East (Academic / other)
• Drugs / interventions: radiation
• Locations: 34 sites (Chiba and 33 other locations)
• Trial ID: NCT05646511 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed rectal adenocarcinoma and no prior treatment.

Not a fit: Patients with distant metastases or those who have previously received radiation therapy to the pelvis will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve treatment outcomes and quality of life for patients with locally advanced rectal cancer by reducing the need for radical surgery.

How similar studies have performed: Previous studies have shown promising results with similar approaches, particularly the PRODIGE-23 trial, indicating potential for success in this area.

Eligibility criteria

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 this trial is running

Chiba and 33 other locations

• 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)
• Hirosaki University Hospital — Hirosaki, Japan (Recruiting)
• Hiroshima University Hospital — Hiroshima, Japan (Recruiting)
• St. Marianna University Hospital — Kawasaki, Japan (Recruiting)
• University of Occupational and Environmental Health Hospital — Kitakyushu, Japan (Recruiting)
• Kochi Medical School Hospital — Kochi, Japan (Recruiting)
• Kumamoto University Hospital — Kumamoto, Japan (Recruiting)
• Kyoto Prefectural University of Medicine — Kyoto, Japan (Recruiting)
• Nagoya University Hospital — Nagoya, Japan (Recruiting)
• Ohara Memorial Kurashiki Central Medical Organization Kurashiki Central Hospital — Okayama, Japan (Recruiting)
• Okayama University Hospital — Okayama, Japan (Recruiting)
• Kansai Medical University Hospital — Osaka, Japan (Recruiting)
• Kindai University Hospital — Osaka, Japan (Recruiting)
• National Hospital Organization Osaka Medical Center — Osaka, Japan (Recruiting)
• Osaka International Cancer Institute — Osaka, Japan (Recruiting)
• Osaka Metropolitan University Hospital — Osaka, Japan (Recruiting)
• Osaka Prefectural Hospital Organization Osaka Acute and General Medical Center — Osaka, Japan (Recruiting)
• Osaka University Hospital — Osaka, Japan (Recruiting)
• Kitasato University Hospital — Sagamihara, Japan (Recruiting)
• Sapporo Medical University Hospital — Sapporo, Japan (Recruiting)
• Keio University Hospital — Tokyo, Japan (Recruiting)
• National Cancer Center Hospital — Tokyo, Japan (Recruiting)
• Nippon Medical School Hospital — Tokyo, Japan (Recruiting)
• Tokyo Medical University Hospital — Tokyo, Japan (Recruiting)
• Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Komagome Hospital — Tokyo, Japan (Recruiting)
• Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center — Yokohama, Japan (Recruiting)
• Yokohama City University Hospital — Yokohama, Japan (Recruiting)
• Yokohama City University Medical Center — Yokohama, Japan (Recruiting)
• Federation of National Public Service Personnel Mutual Aid Associations Yokosuka Mutual Aid Hospital — Yokosuka, Japan (Recruiting)

Study contacts

• Study coordinator: Yoshinori Kagawa, MD., PhD

Conditions Locally Advanced Rectal Cancer; Radiation; CAPOXIRI; CAPOX; Rectal cancer; Total neoadjuvant therapy; Rectal Neoplasms; Colorectal Neoplasms