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

July 13, 2021 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Age ≥18 years and ≤75 years
  2. Histologically and radiologically confirmed colorectal adenocarcinomaImaging and/or pathology confirmed the presence of distal metastases
  3. Multidisciplinary team (MDT) identifies unresectable metastatic colorectal cancer (mCRC)
  4. RAS and BRAF genes are wild-type
  5. The patient had no previous treatment for mCRC, including chemotherapy, surgery, radiotherapy, hepatic artery chemoembolization (TACE) and targeted therapy
  6. Hematological function was normal (platelet > 90×109/L; White blood cell > 3×109/L; Neutrophil > 1.5×109/L)
  7. Serum bilirubin ≤1.5 times the upper normal value (ULN), transaminase ≤5 times ULN
  8. No ascites, normal coagulation function, albumin ≥35g/L
  9. Child-push liver function was rated A
  10. Serum creatinine is below the upper normal limit (ULN) or the calculated creatinine clearance rate of > 50ml/min (using Cockcroft-Gault formula)
  11. ECOG score 2-0
  12. Life expectancy > 3 months
  13. Sign written informed consent
  14. 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:

  1. Recurrence of primary tumor
  2. Severe arterial embolism or ascites
  3. A tendency to bleed or clotting disorder
  4. Hypertensive crisis or hypertensive encephalopathy
  5. Severe uncontrolled systemic complications such as infection or diabetes
  6. 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
  7. History of central nervous system disease (e.g. primary brain tumor, epilepsy beyond the control of standard treatment, any brain metastasis or stroke)
  8. Other malignancies in the past 5 years (except basal cell carcinoma of skin and/or cervical carcinoma in situ after radical resection)
  9. Received any drug under study or treatment with the same type of drug in the last 28 days before the study
  10. Any residual toxicity from previous chemotherapy (except hair loss), such as peripheral neuropathy ≥NCI CTC v3.0 standard level 2
  11. Is allergic to any of the drugs in the study
  12. Pregnant and lactating women
  13. Inability or unwillingness to comply with research protocols
  14. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Bifico combined with chemotherapy plus targeted therapy
Drug: Bifico combined with chemotherapy plus targeted therapy
Bifico combined with chemotherapy plus targeted therapy
Other Names:
  • Bifico+chemotherapy+targeted therapy
EXPERIMENTAL: chemotherapy plus targeted therapy
Drug: chemotherapy plus targeted therapy
chemotherapy plus targeted therapy
Other Names:
  • chemotherapy+targeted therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
objective response rate
Time Frame: 1 year
the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hebei Medical University Fourth Hospital
Zhejiang University
Cancer Hospital of The University of Chinese Academy of Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2021

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 25, 2022

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 25, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 18, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 15, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 13, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DIFFERENCE

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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