Early Blocking Strategy for Metachronous Liver Metastasis of Colorectal Cancer Based on Pre-hepatic CTC Detection

Sponsor

Liaoning Tumor Hospital & Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05720559

Collaborator

(none)

100

Enrollment

Arms

42.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

In this study, the Quintuple method was applied for early intervention of prehepatic CTC-positive bowel cancer patients without dominant liver metastasis, aiming to explore the blocking effect of the Quintuple method on the metachronous liver metastases of colorectal cancer. A one-arm randomized clinical trial was conducted, and the patients were grouped according to their treatment methods. The patients with metachronous liver metastases were used as the end point of the experiment to evaluate the blocking effect of quintuple therapy.

Condition or Disease	Intervention/Treatment	Phase
Preventive Effect of Quintuple Therapy on Metachronous Liver Metastases in Patients With Colorectal Cancer	Drug: Oxaliplatin Drug: S1 Drug: Cetuximab Drug: Metronidazole Drug: Vitamin A Drug: Folic acid Drug: Capecitabine	Phase 2

Detailed Description

Patients diagnosed with colorectal cancer, clinical stage I to III, underwent radical surgery, and prehepatic CTC≥1 were enrolled. Patients were randomly divided into Conventional treatment group and Quintuple method treatment group. Patients in the Conventional treatment group received conventional treatment according to the NCCN Guidelines for Colorectal Cancer 2023 edition. For patients in the Quintuple method treatment group, Quintuple method intervention was adopted, that is, combined with SOX regimen chemotherapy, low-dose cetuximab targeted therapy and three-drug regimen of folic acid, vitamin A and metronidazole. Specific drug dosages were as follows: SOX regimen was administered every three weeks, d1 was given oxaliplatin intravenously, the dosage was 130mg/ m2 * patient's body surface area, d2-d15 was taken orally by Digio, 20mg three times a day each time. Cetuximab combined with chemotherapy was administered intravenously, once every three weeks, before oxaliplatin, and the dosage was 250mg/ m2 * patient's body surface area. Metronidazole 0.4g/ time, once a day; Vitamin A 25,000 units/time, once a day; Folic acid 0.4mg/ time, once a day. The last three drugs were continued until the end of all chemotherapy cycles. The above regimen lasted for 6 to 8 sessions, and enrolled patients were reviewed every 3 months for colorectal cancer-related tumor markers, including MRI and CT imaging. The primary endpoint was radiographically confirmed metachronous liver metastases, and the secondary endpoint was death, observed for 3 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Early Blocking Strategy for Metachronous Liver Metastasis of Colorectal Cancer Based on Pre-hepatic CTC Detection

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Conventional treatment group Conventional treatment was performed according to the NCCN Guidelines for Colorectal Cancer 2023 Edition	Drug: Oxaliplatin Oxaliplatin via intravenous drip on d1 at a dose of 130mg/m2 × patient 's body surface area Drug: Capecitabine Capecitabine via orally on d2-d15 two times daily at a dose of 1000mg/m2 × patient 's body surface area.
Experimental: Quintuple method treatment group SOX regimen chemotherapy, low dose cetuximab targeted therapy, and folic acid, vitamin A, metronidazole three-drug regimen were combined. Specific drug dosages were as follows: SOX regimen was administered every three weeks, d1 was given oxaliplatin intravenously, the dosage was 130mg/ m2 * patient's body surface area, d2-d15 was taken orally by S1, 20mg three times a day each time. Cetuximab combined with chemotherapy was administered intravenously, once every three weeks, before oxaliplatin, and the dosage was 250mg/ m2 * patient's body surface area. Metronidazole 0.4g/ time, once a day; Vitamin A 25,000 units/time, once a day; Folic acid 0.4mg/ time, once a day. The last three drugs were continued until the end of all chemotherapy cycles. These regimens last for 6 to 8 sessions.	Drug: Oxaliplatin Oxaliplatin via intravenous drip on d1 at a dose of 130mg/m2 × patient 's body surface area Drug: S1 Orally on d2-d15 at 20 mg three times daily Drug: Cetuximab Cetuximab combined with chemotherapy was administered simultaneously, once every three weeks,and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area. Drug: Metronidazole Metronidazole 0.4g/time, qd Drug: Vitamin A Vitamin A 25,000 units/time, qd Drug: Folic acid Folic acid 0.4 mg/time, qd

Arm

Intervention/Treatment

Experimental: Conventional treatment group

Conventional treatment was performed according to the NCCN Guidelines for Colorectal Cancer 2023 Edition

Drug: Oxaliplatin

Oxaliplatin via intravenous drip on d1 at a dose of 130mg/m2 × patient 's body surface area

Drug: Capecitabine

Capecitabine via orally on d2-d15 two times daily at a dose of 1000mg/m2 × patient 's body surface area.

Experimental: Quintuple method treatment group

SOX regimen chemotherapy, low dose cetuximab targeted therapy, and folic acid, vitamin A, metronidazole three-drug regimen were combined. Specific drug dosages were as follows: SOX regimen was administered every three weeks, d1 was given oxaliplatin intravenously, the dosage was 130mg/ m2 * patient's body surface area, d2-d15 was taken orally by S1, 20mg three times a day each time. Cetuximab combined with chemotherapy was administered intravenously, once every three weeks, before oxaliplatin, and the dosage was 250mg/ m2 * patient's body surface area. Metronidazole 0.4g/ time, once a day; Vitamin A 25,000 units/time, once a day; Folic acid 0.4mg/ time, once a day. The last three drugs were continued until the end of all chemotherapy cycles. These regimens last for 6 to 8 sessions.

Drug: Oxaliplatin

Oxaliplatin via intravenous drip on d1 at a dose of 130mg/m2 × patient 's body surface area

Drug: S1

Orally on d2-d15 at 20 mg three times daily

Drug: Cetuximab

Cetuximab combined with chemotherapy was administered simultaneously, once every three weeks,and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area.

Drug: Metronidazole

Metronidazole 0.4g/time, qd

Drug: Vitamin A

Vitamin A 25,000 units/time, qd

Drug: Folic acid

Folic acid 0.4 mg/time, qd

Outcome Measures

Primary Outcome Measures

Metachronous liver metastasis rate [Up to approximately 3 years]
The Metachronous liver metastasis rate is the proportion of CTC-positive patients with metachronous liver metastases after conventional therapy or quintuple method intervention.
Overall Survival (OS) [Up to approximately 3 years]
OS is the time interval from the start of treatment to death due to any reason or lost of follow-up. For subjects who survived or were lost to follow-up by the data analysis cutoff date, survival was truncated by the subject's last known survival time.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ages 18-80 at the time of signing the informed consent;
Histologically or cytologically confirmed adenocarcinoma of the colon or rectum;
Radical surgery has been performed;
Imaging examination showed no liver metastasis;
Prehepatic CTC number ≥1;
The ECOG performance status is 0-1.
No combination of other life-threatening diseases;
Willingness and ability to follow scheduled visits, treatment plans, laboratory tests and other research procedures.

Exclusion Criteria:

Patients with non-primary colorectal cancer;
Patients with liver metastasis or other organ metastasis;
Patients without prehepatic CTC or whose prehepatic CTC were negative;
People who are severely allergic to one or more of the drugs required in the test;
Patients with severe underlying diseases of respiratory, circulatory, urinary and hematopoietic systems.