Unresectable Metastatic Colorectal CancerNCT04131803
Probiotics Combined With Standard Chemotherapy Plus Targeted Therapy in Patients With Metastatic Colorectal Cancer
A study testing Bifico combined with chemotherapy plus targeted therapy and chemotherapy plus targeted therapy in people with Unresectable Metastatic Colorectal Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Unresectable Metastatic Colorectal Cancer
- What is being tested?
- Bifico combined with chemotherapy plus targeted therapy and chemotherapy plus targeted therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2021to 25 Nov 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
About this study
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
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.
Read the 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.
- Being tested
- Bifico combined with chemotherapy plus targeted therapy, chemotherapy plus targeted therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bifico combined with chemotherapy plus targeted therapyDrug
Also called Bifico+chemotherapy+targeted therapy
Bifico combined with chemotherapy plus targeted therapy
chemotherapy plus targeted therapyDrug
Also called chemotherapy+targeted therapy
chemotherapy plus targeted therapy
| Study group | Role | What they receive |
|---|---|---|
| Bifico combined with chemotherapy plus targeted therapy | Experimental | Bifico combined with chemotherapy plus targeted therapy Receives: Drug: Bifico combined with chemotherapy plus targeted therapy |
| chemotherapy plus targeted therapy | Experimental | chemotherapy plus targeted therapy Receives: Drug: chemotherapy plus targeted therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response rate
the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2019
- Study start1 Oct 2021 (estimated)
- Primary completion25 Nov 2022 (estimated)
- Study completion25 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Zhejiang University, Zhejiang Cancer Hospital, Hebei Medical University Fourth Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04131803
- Sponsor's protocol ID
- DIFFERENCE
- Status last verified
- Oct 2020
- First submitted
- 15 Oct 2019
- Last updated
- 15 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04131803
- Acronym / sponsor ID
- DIFFERENCE
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Zhejiang University, Zhejiang Cancer Hospital, Hebei Medical University Fourth Hospital
- Study start
- 1 Oct 2021 (estimated)
- Primary completion
- 25 Nov 2022 (estimated)
- Study completion
- 25 Nov 2025 (estimated)
- First posted
- 18 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bifico combined with chemotherapy plus targeted therapy | Experimental | Drug: Bifico combined with chemotherapy plus targeted therapyBifico combined with chemotherapy plus targeted therapy |
| chemotherapy plus targeted therapy | Experimental | Drug: chemotherapy plus targeted therapychemotherapy plus targeted therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bifico combined with chemotherapy plus targeted therapyAlso: Bifico+chemotherapy+targeted therapyBifico combined with chemotherapy plus targeted therapy | Drug | Bifico combined with chemotherapy plus targeted therapy |
| chemotherapy plus targeted therapyAlso: chemotherapy+targeted therapychemotherapy plus targeted therapy | Drug | chemotherapy plus targeted therapy |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Bifico combined with chemotherapy plus targeted therapy and chemotherapy plus targeted therapy in people with Unresectable Metastatic Colorectal Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
objective response rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.