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
Sponsored by
About this trial
This is an interventional treatment trial for Unresectable Metastatic Colorectal Cancer
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
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
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
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
No
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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