TNT of SCRT+CAPOX Vs SCRT+CAPOXIRI for Locally Advanced Rectal Cancer

Last updated: September 24, 2024
Sponsor: National Cancer Center Hospital East
Overall Status: Active - Recruiting

Phase

3

Condition

Rectal Cancer

Colon Cancer

Colorectal Cancer

Treatment

CAPOXIRI

CAPOX

SCRT

Clinical Study ID

NCT05646511
K2022001
jRCTs031220342
  • Ages > 18
  • All Genders

Study Summary

This trial is a multicenter randomized Phase III study to verify the superiority of short-course preoperative radiation (SCRT) and CAPOXIRI over SCRT and CAPOX as preoperative treatments for locally advanced rectal cancer.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. The content of this research was fully explained, and written informed consent wasobtained from the subject.

  2. Histologically confirmed rectal adenocarcinoma.

  3. Radical resection is clinically possible without any distant metastases on imagingstudies.

  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 onconsent 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 cancertypes.

  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) -, mesorectalfascia (MRF) clear and 10 cm < AV ≤ 12 cm, T3a/bN0-1M0, EMVI-, MRF clear areeligible only for those who refused surgery)

  1. UGT1A1 is wild-type or single heterozygous.

  2. Criteria for major organ function within 28 days prior to enrollment. If there aremultiple test results within this period, the most recent one will be used, andblood transfusions and hematopoietic factor preparations will not be administeredwithin 14 days before the test date for measurements before registration.

  3. Neutrophil count: ≥1,500/mm3

  4. Platelet count: ≥10.0×10 4/mm3

  5. Hemoglobin concentration: ≥9.0 g/dL

  6. Total bilirubin: ≤2.0 mg/dL

  7. Aspartate transaminase (AST): ≤100 IU/L or less

  8. Alanine transaminase (ALT): ≤100 IU/L or less

  9. Serum creatinine: Creatinine clearance ≥30 mL/min (by Cockcroft & Gaultformula)

Exclusion

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 activeinflammatory bowel disease).

  6. Patients with multiple active cancers (simultaneous multiple cancers or metachronousmultiple cancers with a disease-free interval of 5 years or less). However,carcinoma in situ or lesions equivalent to intramucosal carcinoma, which can becured by local treatment, are not treated as active multiple cancers.

  7. Pregnant women, lactating women, positive pregnancy test, or unwillingness to usecontraception.

  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 clinicalsignificance using clinical specimens from cancer patients" for whole-genomeanalysis based on the "Action Plan for Whole-Genome Analysis, etc." (CONDUCTORstudy).

  12. Any other patients the principal investigator or co-investigator deems inappropriatefor study participation.

Study Design

Total Participants: 608
Treatment Group(s): 3
Primary Treatment: CAPOXIRI
Phase: 3
Study Start date:
November 21, 2022
Estimated Completion Date:
December 31, 2030

Study Description

Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) has the promise, which means non-operative management (NOM) enable more patients (pts) with a complete clinical response (cCR) or near-complete clinical responses (nCR) after TNT to avoid subsequent radical surgery, with potentially maintaining anorectal function and quality of life (QoL). Recently, PRODIGE-23 trial demonstrated that triplet regimen (Irinotecan, oxaliplatin and fluoropyrimidine) before preoperative chemoradiotherapy (CRT) significantly improved outcomes compared with CRT. However, there has been no prospective study comparing consolidation triplet with doublet regimens following short course radiotherapy (SCRT). The aim of this randomized phase III trial is to test superiority of consolidation irinotecan, capecitabine and oxaliplatin (CAPOXIRI) vs. capecitabine and oxaliplatin (CAPOX) following SCRT as TNT in pts with LARC.

Pts in both groups will be re-staged after completing TNT before radical surgery according to the Memorial Sloan Kettering Regression Schema; pts with incomplete response (iCR) will undergo total mesorectal excision (TME), cCR pts will receive NOM, and nCR pts will undergo TME or NOM by a physician discretion under the recommendation of blind assessment by the designated NOM central committee. Pts will be followed by CT, MRI, colonoscopy and liquid biopsy every 4 months for 2 years, and every 6 months thereafter up to 5 years.

To detect a decrease in 3-year cumulative probability of organ preservation-adapted Disease free survival (DFS) from 75.0% to 81.7%, corresponding to a target hazard ratio of 0·70, a total of 608 pts (196 events) would achieve 70% power at a two-sided α significance level of 0.05.

Connect with a study center

  • National Cancer Center Hospital East

    Chiba,
    Japan

    Active - Recruiting

  • Ehime Prefectural Central Hospital

    Ehime,
    Japan

    Active - Recruiting

  • Kyushu University Hospital

    Fukuoka,
    Japan

    Active - Recruiting

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka,
    Japan

    Active - Recruiting

  • National Hospital Organization Kyushu Medical Center

    Fukuoka,
    Japan

    Active - Recruiting

  • Gifu University Hospital

    Gifu,
    Japan

    Active - Recruiting

  • Hirosaki University Hospital

    Hirosaki,
    Japan

    Active - Recruiting

  • Hiroshima University Hospital

    Hiroshima,
    Japan

    Active - Recruiting

  • St. Marianna University Hospital

    Kawasaki,
    Japan

    Active - Recruiting

  • University of Occupational and Environmental Health Hospital

    Kitakyushu,
    Japan

    Active - Recruiting

  • Kochi Medical School Hospital

    Kochi,
    Japan

    Active - Recruiting

  • Kumamoto University Hospital

    Kumamoto,
    Japan

    Active - Recruiting

  • Nagoya University Hospital

    Nagoya,
    Japan

    Active - Recruiting

  • Ohara Memorial Kurashiki Central Medical Organization Kurashiki Central Hospital

    Okayama,
    Japan

    Active - Recruiting

  • Okayama University Hospital

    Okayama,
    Japan

    Active - Recruiting

  • Kansai Medical University Hospital

    Osaka,
    Japan

    Active - Recruiting

  • Kindai University Hospital

    Osaka,
    Japan

    Active - Recruiting

  • National Hospital Organization Osaka Medical Center

    Osaka,
    Japan

    Active - Recruiting

  • Osaka International Cancer Institute

    Osaka,
    Japan

    Active - Recruiting

  • Osaka Prefectural Hospital Organization Osaka Acute and General Medical Center

    Osaka,
    Japan

    Active - Recruiting

  • Osaka University Hospital

    Osaka,
    Japan

    Active - Recruiting

  • Kitasato University Hospital

    Sagamihara,
    Japan

    Active - Recruiting

  • Sapporo Medical University Hospital

    Sapporo,
    Japan

    Active - Recruiting

  • Shizuoka Cancer Center

    Shizuoka,
    Japan

    Site Not Available

  • Foundation for Cancer Research Ariake Hospital

    Tokyo,
    Japan

    Active - Recruiting

  • Keio University Hospital

    Tokyo,
    Japan

    Active - Recruiting

  • National Cancer Center Hospital

    Tokyo,
    Japan

    Active - Recruiting

  • Nippon Medical School Hospital

    Tokyo,
    Japan

    Active - Recruiting

  • Tokyo Medical University Hospital

    Tokyo,
    Japan

    Active - Recruiting

  • Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Komagome Hospital

    Tokyo,
    Japan

    Active - Recruiting

  • Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center

    Yokohama,
    Japan

    Active - Recruiting

  • Yokohama City University Hospital

    Yokohama,
    Japan

    Active - Recruiting

  • Yokohama City University Medical Center

    Yokohama,
    Japan

    Active - Recruiting

  • Federation of National Public Service Personnel Mutual Aid Associations Yokosuka Mutual Aid Hospital

    Yokosuka,
    Japan

    Active - Recruiting

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