Total Neoadjuvant Therapy of SCRT+CAPOX vs SCRT+CAPOXIRI for Locally Advanced Rectal Cancer (ENSEMBLE) (ENSEMBLE)
Locally Advanced Rectal Cancer
About this trial
This is an interventional treatment trial for Locally Advanced Rectal Cancer focused on measuring Radiation, CAPOXIRI, CAPOX, Rectal cancer, Total neoadjuvant therapy, Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Capecitabine, Oxaliplatin, Irinotecan, Antineoplastic Agents, Chemotherapy, Non-operative management, Surgery, MRI, Restaging, QOL, Organ preservation
Eligibility Criteria
Inclusion Criteria: The content of this research was fully explained, and written informed consent was obtained from the subject. Histologically confirmed rectal adenocarcinoma. Radical resection is clinically possible without any distant metastases on imaging studies. Age of 18 years or older on the date of consent acquisition. Eastern Cooperative Oncology Group (ECOG) PS 0-1 (PS 0 if aged 70 years or older on consent acquisition date). Inferior margin of the tumor is within 12 cm of the AV. No prior tumor treatment. No history of radiation therapy to the pelvis, including treatment for other cancer types. 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) UGT1A1 is wild-type or single heterozygous. 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. Neutrophil count: ≥1,500/mm3 Platelet count: ≥10.0×10 4/mm3 Hemoglobin concentration: ≥9.0 g/dL Total bilirubin: ≤2.0 mg/dL Aspartate transaminase (AST): ≤100 IU/L or less Alanine transaminase (ALT): ≤100 IU/L or less Serum creatinine: Creatinine clearance ≥30 mL/min (by Cockcroft & Gault formula) Exclusion Criteria: Extensive surgery (excluding colostomy and central venous port construction) within 4 weeks before starting protocol treatment. Complications or history of severe lung disease (such as interstitial pneumonia, pulmonary fibrosis, and severe emphysema). Colonic stent in place. Contraindications for MRI such as cardiac pacemakers. Serious comorbidities (such as heart failure, renal failure, liver failure, intestinal paralysis, intestinal obstruction, uncontrolled diabetes, and active inflammatory bowel disease). 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. Pregnant women, lactating women, positive pregnancy test, or unwillingness to use contraception. Hepatitis B surface (HBs) antigen positive or hepatitis C virus (HCV) antibody-positive. However, HCV-RNA-negative can be registered. Have human immunodeficiency virus (HIV) infection. MSI-high (MSI-H) or defective mismatch repair (dMMR) is known. 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). Any other patients the principal investigator or co-investigator deems inappropriate for study participation.
Sites / Locations
- National Cancer Center Hospital EastRecruiting
- Kyushu University HospitalRecruiting
- National Hospital Organization Kyushu Cancer CenterRecruiting
- National Hospital Organization Kyushu Medical CenterRecruiting
- Gifu University HospitalRecruiting
- Hirosaki University HospitalRecruiting
- Hiroshima University HospitalRecruiting
- St. Marianna University HospitalRecruiting
- University of Occupational and Environmental Health HospitalRecruiting
- Nagoya University HospitalRecruiting
- Ohara Memorial Kurashiki Central Medical Organization Kurashiki Central HospitalRecruiting
- Kindai University HospitalRecruiting
- National Hospital Organization Osaka Medical CenterRecruiting
- Osaka Prefectural Hospital Organization Osaka Acute and General Medical CenterRecruiting
- Osaka University HospitalRecruiting
- Kitasato University HospitalRecruiting
- Sapporo Medical University HospitalRecruiting
- Foundation for Cancer Research Ariake HospitalRecruiting
- Keio University HospitalRecruiting
- National Cancer Center HospitalRecruiting
- Nippon Medical School HospitalRecruiting
- Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Komagome HospitalRecruiting
- Kanagawa Prefectural Hospital Organization Kanagawa Cancer CenterRecruiting
- Yokohama City University HospitalRecruiting
- Yokohama City University Medical CenterRecruiting
- Federation of National Public Service Personnel Mutual Aid Associations Yokosuka Mutual Aid HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Control arm SCRT+CAPOX
Experimental arm SCRT+CAPOXIRI
The standard-of-care group receives short-course radiation therapy (5 × 5 Gy) followed by six cycles of CAPOX (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, q3wks).
The standard-of-care group receives short-course radiation therapy (5 × 5 Gy) followed by six cycles of CAPOX (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, q3wks).