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Probiotics Combined With Standard Chemotherapy Plus Targeted Therapy in Patients With Metastatic Colorectal Cancer

Primary Purpose

Unresectable Metastatic Colorectal Cancer

Status

Not yet recruiting

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Bifico combined with chemotherapy plus targeted therapy

chemotherapy plus targeted therapy

About this trial

This is an interventional treatment trial for Unresectable Metastatic Colorectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Age ≥18 years and ≤75 years
Histologically and radiologically confirmed colorectal adenocarcinomaImaging and/or pathology confirmed the presence of distal metastases
Multidisciplinary team (MDT) identifies unresectable metastatic colorectal cancer (mCRC)
RAS and BRAF genes are wild-type
The patient had no previous treatment for mCRC, including chemotherapy, surgery, radiotherapy, hepatic artery chemoembolization (TACE) and targeted therapy
Hematological function was normal (platelet > 90×109/L; White blood cell > 3×109/L; Neutrophil > 1.5×109/L)
Serum bilirubin ≤1.5 times the upper normal value (ULN), transaminase ≤5 times ULN
No ascites, normal coagulation function, albumin ≥35g/L
Child-push liver function was rated A
Serum creatinine is below the upper normal limit (ULN) or the calculated creatinine clearance rate of > 50ml/min (using Cockcroft-Gault formula)
ECOG score 2-0
Life expectancy > 3 months
Sign written informed consent
Willing and able to receive follow-up until death or study completion or study termination

Exclusion criteria:

Patients who meet any of the following criteria will be excluded from the study:

Recurrence of primary tumor
Severe arterial embolism or ascites
A tendency to bleed or clotting disorder
Hypertensive crisis or hypertensive encephalopathy
Severe uncontrolled systemic complications such as infection or diabetes
Clinically serious cardiovascular diseases such as cerebrovascular accident (within 6 months before enrollment), myocardial infarction (within 6 months before enrollment), uncontrolled hypertension after appropriate drug treatment, unstable angina, congestive heart failure (nyha2-4), and arrhythmia requiring drug treatment
History of central nervous system disease (e.g. primary brain tumor, epilepsy beyond the control of standard treatment, any brain metastasis or stroke)
Other malignancies in the past 5 years (except basal cell carcinoma of skin and/or cervical carcinoma in situ after radical resection)
Received any drug under study or treatment with the same type of drug in the last 28 days before the study
Any residual toxicity from previous chemotherapy (except hair loss), such as peripheral neuropathy ≥NCI CTC v3.0 standard level 2
Is allergic to any of the drugs in the study
Pregnant and lactating women
Inability or unwillingness to comply with research protocols
The presence of any other disease, dysfunction due to metastatic lesions, or a suspected medical condition indicated a possible contraindication to the use of the study drug or a population at high risk for treatment-related complications

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Bifico combined with chemotherapy plus targeted therapy

chemotherapy plus targeted therapy

Arm Description

Bifico combined with chemotherapy plus targeted therapy

chemotherapy plus targeted therapy

Outcomes

Primary Outcome Measures

objective response rate

the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period

Secondary Outcome Measures

Full Information

NCT ID

NCT04131803

First Posted

October 15, 2019

Last Updated

July 13, 2021

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

Zhejiang University, Cancer Hospital of The University of Chinese Academy of Sciences, Hebei Medical University Fourth Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04131803

Brief Title

Probiotics Combined With Standard Chemotherapy Plus Targeted Therapy in Patients With Metastatic Colorectal Cancer

Official Title

Efficacy and Safety of Probiotics Combined With Standard Chemotherapy Plus Targeted Therapy in Patients With Metastatic Colorectal Cancer: A Prospective, Open-Label，Randomized, Multi-center Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 1, 2021 (Anticipated)

Primary Completion Date

November 25, 2022 (Anticipated)

Study Completion Date

November 25, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

Zhejiang University, Cancer Hospital of The University of Chinese Academy of Sciences, Hebei Medical University Fourth Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Bifico (also known as "bifidobacterium trifidum live powder") is a probiotic preparation that has been marketed and widely used in China. The number of live bacteria of lactobacillus acidophilus and bifidobacterium per gram should not be less than 1.0×107CFU. At present, it is mainly used for diarrhea and abdominal distension caused by intestinal flora imbalance. It can also be used for treating mild to moderate acute diarrhea and chronic diarrhea. Lactobacillus acidophilus and bifidobacteria have been fully proved in basic studies to improve gut microbiological environment and inhibit colorectal cancer. A recent paper published by Nature Biomedical Engineering reported that chemotherapy can effectively enhance the efficacy of colon cancer by regulating intestinal flora. Based on the above evidence, we propose that the current standard chemotherapy plus targeted therapy regimen combined with Bifico can exert a more powerful synergistic anticancer effect. To sum up, this study put forward innovative joint regulating intestinal flora environment with standard chemotherapy and target therapy of new concept and mode, to assess Bifico combined with standard chemotherapy plus targeted therapy compared to standard chemotherapy plus targeted therapy for efficacy and safety of metastatic colorectal cancer, combined with the intestinal flora, probiotics patient blood DNA analysis, etc. New technology, explore flora index correlation with the prognosis of patients' immune system function, and its potential as a predictive marker. It is worth noting that this study will closely combine the current most advanced intestinal flora 16S microbial polymorphism detection and single-cell sequencing technology, so as to truly achieve accurate and individualized treatment, evaluation and prognosis prediction.

Detailed Description

Patients were randomized to either standard therapy (i.e., chemotherapy + targeted therapy) or standard therapy combined with Bifico. We will provide patients with first-line, second-line and third-line treatment with full intervention, including maintenance treatment. The standard treatment regimen, first-line (FOLFOX regimen + cetuximab) : oxaliplatin 85mg/m2 intravenous infusion 2 hours day1 + calcium leucofolate (LV) 400mg/m2 intravenous infusion 2 hours day1 + 5-fluorouracil (5-fu) 400mg/m2 intravenous infusion day 1, and then 1200mg/ (m2·day) ×2 days continuous intravenous infusion + cetuximab 500mg/m2 intravenous infusion over 2 hours day 1, repeat every 2 weeks. First-line treatment 4 to 6 months after the effective disease control or stable but still no radical surgery opportunity, can enter maintenance treatment: 5 - FU + LV (dose with a line), repeat every 2 weeks, or capecitabine oral 2 1250 mg/m2 / day day 1-14 + beacizumab 7.5 mg/kg intravenous day 1, repeat every 3 weeks, or stop the systemic treatment, until a progression, and immediately to the next line treatment; Second-line (FOLFIRI regimen + bevacizumab) : irinotegam 180 mg/m2 iv infusion over 30-90min day 1 + LV 400mg/m2 iv infusion 2 hours day 1 + 5-fu400 mg/m2 iv infusion day 1, then 1200mg/ (m2·day) ×2 days continuous intravenous infusion + bevacizumab 5mg/kg introvenious infusion day 1, repeat every 2 weeks. Third line: fuquinib 160mg oral 1/ day day 1-21, repeat every 28 days, or regofenil 5mg oral 1/ day day 1-21, repeat every 28 days. Bifico 2g oral 3/ day, take the medicine daily.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Unresectable Metastatic Colorectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Bifico combined with chemotherapy plus targeted therapy

Arm Type

Experimental

Arm Description

Bifico combined with chemotherapy plus targeted therapy

Arm Title

chemotherapy plus targeted therapy

Arm Type

Experimental

Arm Description

chemotherapy plus targeted therapy

Intervention Type

Drug

Intervention Name(s)

Bifico combined with chemotherapy plus targeted therapy

Other Intervention Name(s)

Bifico+chemotherapy+targeted therapy

Intervention Description

Bifico combined with chemotherapy plus targeted therapy

Intervention Type

Drug

Intervention Name(s)

chemotherapy plus targeted therapy

Other Intervention Name(s)

chemotherapy+targeted therapy

Intervention Description

chemotherapy plus targeted therapy

Primary Outcome Measure Information:

Title

objective response rate

Description

the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Age ≥18 years and ≤75 years Histologically and radiologically confirmed colorectal adenocarcinomaImaging and/or pathology confirmed the presence of distal metastases Multidisciplinary team (MDT) identifies unresectable metastatic colorectal cancer (mCRC) RAS and BRAF genes are wild-type The patient had no previous treatment for mCRC, including chemotherapy, surgery, radiotherapy, hepatic artery chemoembolization (TACE) and targeted therapy Hematological function was normal (platelet > 90×109/L; White blood cell > 3×109/L; Neutrophil > 1.5×109/L) Serum bilirubin ≤1.5 times the upper normal value (ULN), transaminase ≤5 times ULN No ascites, normal coagulation function, albumin ≥35g/L Child-push liver function was rated A Serum creatinine is below the upper normal limit (ULN) or the calculated creatinine clearance rate of > 50ml/min (using Cockcroft-Gault formula) ECOG score 2-0 Life expectancy > 3 months Sign written informed consent Willing and able to receive follow-up until death or study completion or study termination Exclusion criteria: Patients who meet any of the following criteria will be excluded from the study: Recurrence of primary tumor Severe arterial embolism or ascites A tendency to bleed or clotting disorder Hypertensive crisis or hypertensive encephalopathy Severe uncontrolled systemic complications such as infection or diabetes Clinically serious cardiovascular diseases such as cerebrovascular accident (within 6 months before enrollment), myocardial infarction (within 6 months before enrollment), uncontrolled hypertension after appropriate drug treatment, unstable angina, congestive heart failure (nyha2-4), and arrhythmia requiring drug treatment History of central nervous system disease (e.g. primary brain tumor, epilepsy beyond the control of standard treatment, any brain metastasis or stroke) Other malignancies in the past 5 years (except basal cell carcinoma of skin and/or cervical carcinoma in situ after radical resection) Received any drug under study or treatment with the same type of drug in the last 28 days before the study Any residual toxicity from previous chemotherapy (except hair loss), such as peripheral neuropathy ≥NCI CTC v3.0 standard level 2 Is allergic to any of the drugs in the study Pregnant and lactating women Inability or unwillingness to comply with research protocols The presence of any other disease, dysfunction due to metastatic lesions, or a suspected medical condition indicated a possible contraindication to the use of the study drug or a population at high risk for treatment-related complications

12. IPD Sharing Statement

Learn more about this trial

Probiotics Combined With Standard Chemotherapy Plus Targeted Therapy in Patients With Metastatic Colorectal Cancer

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