Perioperative chemotherapy and surgery vs. upfront surgery followed by adjuvant chemotherapy for patients with initial resectable colorectal liver metastases: A multi-center randomized controlled trial

JRCT ID: jRCTs031230683

Registered date:07/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: colorectal cancer liver metastases
• Date of first enrollment: 07/03/2024
• Target sample size: 510
• Study type: Interventional

Intervention(s)

(1) FOLFOX (4 courses) or CAPOX (3 courses) as preoperative chemotherapy.
(2) Liver resection is performed.
After hepatectomy, either FOLFOX (12 courses), CAPOX (8 courses), or UFT/LV (5 courses) should be administered as postoperative adjuvant chemotherapy.

Outcome(s)

• Primary Outcome: 3-year progression-free survival (PFS)

Secondary Outcome

(1) 5-year overall survival (OS)
(2) 5-year progression-free survival (PFS)
(3) Dose intensity
(4) Frequency of recurrence (form, resection rate)
(5) R0 liver resection rate
(6) Change in nutritional index (Alb) (laboratory values at the end of adjuvant chemotherapy - laboratory values at the time of allocation)
(7) Change in tumor marker (CEA) (laboratory values at the end of adjuvant chemotherapy - laboratory values at the time of allocation)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Patients who are diagnosed with first colorectal cancer liver metastases by images (Dynamic CT or EOB-MRI) (including simultaneous liver metastases and metachronous liver metastases)
(2) Patients who have no no uncontrolled distant extrahepatic metastases or recurrence with contrast-enhanced CT scan of the chest to pelvis within 28 days prior to enrollment (However, plain CT is acceptable if a patient is allergic to contrast agent.)
(3) The number of liver metastases must be between 3 and 10.
(4) The applicant must be at least 18 years of age at the time of consent (no upper age limit is set).
(5) Any gender
(6) Eastern Cooperative Group Performance Status (PS) of 0 or 1
(7) Patients with proper organ function
(i)White blood cell count must must be over 4,000, white blood cell count must be under 12,000/mm2
(ii)Hemoglobin must be over 9.0 g/dL
(iii)Platelet count must be over 100,000/mm2
(iv)Total bilirubin must be under 1.5mg/dL
(v)Serum albumin must be over 3.0g/dL
(vi)AST (GOT), ALT (GPT) and ALP must be under 5 times the upper limit of the reference value of each medical institution (except in the case of elevated laboratory values due to cancer)
(vii) Estimated glomerular filtration rate must be over 60 ml/min/1.73 m2
(8) Child-Pugh score must be 5 to 6
(9) ICG-15 must be under 20% or value converted to ICG-15 by other tests must be under 20%
(10) Patients who have received a full explanation of the study and have given written consent of their own free will after full understanding of the study.

Exclude criteria

(1) Persons with active multiple cancers (synchronous multiple cancers and iatrogenic multiple cancers with a disease-free period of 5 years or less. except that intraepithelial or intramucosal carcinoma-equivalent lesions of any organ that are considered curable with local treatment may be registered)
(2) Patients with distant metastasis other than liver cancer.
(3) Patients who have relapsed within 180 days of completion of adjuvant chemotherapy with oxaliplatin-containing regimen after resection of colorectal cancer.
(4) Patients with concurrent liver metastases whose colorectal cancer is associated with bleeding or obstruction and who undergo simultaneous resection of the primary tumor and metastases (patients are not excluded if the primary tumor is resected first)
(5) Patients with severe sensory or perceptual abnormalities with functional impairment
(6) Patients with a history of hypersensitivity to fluorouracil, calcium levofolinate, capecitabine, oxaliplatin, components of tegafur-uracil or other platinum-containing drugs
(7) Patients with a history of serious drug allergy such as anaphylactic shock or a history of serious adverse drug reactions
(8) Patients with diarrhea that causes poor oral intake
(9) Patients with a large amount of ascites or pleural effusion
(10) Patients with acute coronary syndrome, uncontrolled arrhythmia, heart failure, valvular disease, or a history of myocardial infarction or heart failure within 3 months.
(11) Patients who are receiving Tegafur, Gimerasil, Oterasil, or Potassium potassium combination drug or who have stopped taking it within 7 days after discontinuation.
(12) Women who are pregnant or lactating.
(13) Males who wish to have a child
(14) Patients with interstitial pneumonia, pulmonary fibrosis, or severe emphysema
(15) Patients with psychosis or psychiatric symptoms that make it difficult for them to participate in the study.
(16) Any other person who is judged by the principal investigator or subinvestigator to be inappropriate to participate in this study.

Related Information

• Primary Sponsor: Hasegawa Kiyoshi
• Source(s) of Monetary Support: JSS Clinical Investigation Project Award,Surgical Research Grant Fund in honor of the Japan Surgical Society of Regular Academic Congress