Colorectal CarcinomaPhase 3NCT04781270
mFOLFOXIRI+Bev vs. mFOLFOX6+Bev for RAS Mutant Unresectable Colorectal Liver-limited Metastases
A Phase 3 study testing mFOLFOXIRI regimen, mFOLFOX regimen and Bevacizumab in people with Colorectal Carcinoma and Liver Metastases, run by Fudan University at 1 site in China.
Trial summary
Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by conversion therapy. However, the optimal regimen of conversion therapy for RAS mutant patients has not been defined. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Carcinoma, Liver Metastases
- What is being tested?
- mFOLFOXIRI regimen, mFOLFOX regimen and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 308 participants
- Where
- 1 siteChina
- Study dates
- 15 Apr 2021to 30 Mar 2026
- Phase
- Phase 3
- 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
- Histological proof of colorectal adenocarcinoma;
- Age ≥ 18 years and ≤75 years;
- Simultaneous liver-limited metastases;
- Initially unresectable liver metastases determined by a local MDT;
- RAS mutation and BRAF V600E wild-type;
- At least one measurable liver metastasis;
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- Initially resectable primary tumor or primary tumor already resected;
- World Health Organization (WHO) performance status 0-1;
- Life expectancy ≥ 3 months;
- Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl;
- Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min;
- Written informed consent.
Who cannot join
- Previous systemic treatment for metastatic disease;
- Previous surgery for metastatic disease;
- Extrahepatic metastases;
- Unresectable primary tumor;
- Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation;
- Acute or subacute intestinal obstruction;
Show all 12Show fewer
- Second primary malignancy within the past 5 years;
- Drug or alcohol abuse;
- No legal capacity or limited legal capacity;
- Pregnant or lactating women;
- Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs;
- Peripheral neuropathy;
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200032
Jianmin Xu, M.D. Ph.D, xujmin@aliyun.com
Wentao Tang, M.D. Ph.D, tangwt1988@163.com
About this study
Official title: mFOLFOXIRI Plus Bevacizumab Versus mFOLFOX6 Plus Bevacizumab for the First Line Treatment of RAS Mutant Unresectable Colorectal Liver-limited Metastases
Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by conversion therapy. However, the optimal regimen of conversion therapy for RAS mutant patients has not been defined.
In this study colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be tested for RAS and BRAF tumor mutation status. Patients with RAS mutant and BRAF wild type will be randomised between modified FOLFOXIRI (mFOLFOXIRI) plus bevacizumab and modified FOLFOX6 (mFOLFOX6) plus bevacizumab. Patient imaging will be reviewed for resectability by MDT, consisting of at least one radiologist and three liver surgeons every assessment. MDT review will be performed prior to randomization as well as during treatment, as described in the protocol.
Read the detailed description
Patients will be stratified for primary tumor location (right-sided or left sided), numbers of liver metastases (<5 or ≥5) and primary tumor resected or unresected.
Patients with RAS mutated primary tumors will be randomized between mFOLFOXIRI plus bevacizumab (Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by irinotecan 165 mg/m^2 i.v. in 60 minutes, followed by oxaliplatin 85 mg/m^2 i.v. together with leucovorin 400 mg/m^2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 2400 mg/m^2 in 46 hours, every 2 weeks) or mFOLFOX6 plus bevacizumab (Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by oxaliplatin 85 mg/m^2 i.v. together with leucovorin 400 mg/m^2 i.v. in 120 minutes, followed by bolus 5FU 400 mg/m^2, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m^2 in 46 hours, every 2 weeks).
Patients will be evaluated every 8 weeks by MRI or CT scan for disease status. The assigned systemic treatment should be continued for at least 6 months or earlier in case of resectability, progression of disease, unacceptable toxicity, or patient refusal. If after 6 months MDT concludes that the patient is still not resectable, it is highly unlikely that resectability will be achieved at all. Therefore the chemotherapy regimen may be reconsidered after 6 months of treatment. These patients will continue with bevacizumab plus fluoropyrimidine until progression or unacceptable toxicity.
In patients who will become resectable and undergo secondary surgery of liver metastases, the total duration of preoperative and postoperative treatment together should be 6 months. However, in these patients mFOLFOXIRI should not be continued after surgery and replaced by mFOLFOX6. Bevacizumab will continued after surgery for both groups.
- Conditions
- Colorectal Carcinoma, Liver Metastases
- Being tested
- mFOLFOXIRI regimen, mFOLFOX regimen, Bevacizumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mFOLFOXIRI regimenDrug
oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1
mFOLFOX regimenDrug
oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1
BevacizumabDrug
5 mg/kg on day 1
| Study group | Role | What they receive |
|---|---|---|
| mFOLFOXIRI+Bev | Experimental | Patients will receive mFOLFOXIRI plus bevacizumab once every two weeks as the first-line treatment.
Drug: mFOLFOXIRI plus Bevacizumab Bevacizumab (5 mg/kg on day 1) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1). A local MDT will assess the efficiency every 4 cycles of the treatment. The maximum period of conversion therapy is 12 cycles. Receives: Drug: mFOLFOXIRI regimen; Drug: Bevacizumab |
| mFOLFOX6+Bev | Active comparator | Patients will receive mFOLFOX6 plus bevacizumab once every two weeks as the first-line treatment.
Drug: mFOLFOX6 Plus Bevacizumab mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1). A local MDT will assess the efficiency every 4 cycles of the treatment. The maximum period of conversion therapy is 12 cycles. Receives: Drug: mFOLFOX regimen; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
conversion resection rate
R0 resection rate upon conversion treatment with chemotherapy plus bevacizumab
Measured: up to 6 months
Secondary outcomes (8)
Overall survival (OS)
from the first day of assigned treatment to death or last known to be alive
Measured: up to 2 years
Progression-free survival (PFS)
from the first day of assigned treatment to progression or death whichever comes first
Measured: up to 2 years
Toxicity (AE)
Patients will be evaluated for Adverse Events at the start of each treatment cycle according to CTCAE version 5.0
Measured: up to 6 months
postoperative complication
Patients will be evaluated for surgical morbidity during 1 month. Postoperative morbidity will be scored according 'Clavien-Dindo Grade'.
Measured: After surgery during one month
overall response
Response according to RECIST 1.1
Measured: up to 6 months
proportion of no evidence of disease
Response according to RECIST 1.1
Measured: up to 6 months
Best deepness of response
The maximum tumor shrinkage rates by Response Evaluation Criteria in Solid Tumors (RECIST) throughout the treatments
Measured: up to 6 months
Early tumor shrinkage
The rates of tumor shrinkage by RECIST at 8 weeks
Measured: at 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2021
- Study start15 Apr 2021
- Primary completion30 Mar 2024 (estimated)
- Study completion30 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CarcinomaStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 308 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jianmin Xu, MD, Ph.D., Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04781270
- Sponsor's protocol ID
- BECOME2
- Status last verified
- Mar 2021
- First submitted
- 1 Mar 2021
- Last updated
- 27 Sep 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- mFOLFOXIRI Plus Bevacizumab Versus mFOLFOX6 Plus Bevacizumab for the First Line Treatment of RAS Mutant Unresectable Colorectal Liver-limited Metastases
- ClinicalTrials.gov ID
- NCT04781270
- Acronym / sponsor ID
- BECOME2
- Conditions
- Colorectal Carcinoma, Liver Metastases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 308 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 15 Apr 2021 (actual)
- Primary completion
- 30 Mar 2024 (estimated)
- Study completion
- 30 Mar 2026 (estimated)
- First posted
- 4 Mar 2021 (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.
Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by conversion therapy. However, the optimal regimen of conversion therapy for RAS mutant patients has not been defined.
In this study colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be tested for RAS and BRAF tumor mutation status. Patients with RAS mutant and BRAF wild type will be randomised between modified FOLFOXIRI (mFOLFOXIRI) plus bevacizumab and modified FOLFOX6 (mFOLFOX6) plus bevacizumab. Patient imaging will be reviewed for resectability by MDT, consisting of at least one radiologist and three liver surgeons every assessment. MDT review will be performed prior to randomization as well as during treatment, as described in the protocol.
Detailed description
Patients will be stratified for primary tumor location (right-sided or left sided), numbers of liver metastases (<5 or ≥5) and primary tumor resected or unresected.
Patients with RAS mutated primary tumors will be randomized between mFOLFOXIRI plus bevacizumab (Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by irinotecan 165 mg/m^2 i.v. in 60 minutes, followed by oxaliplatin 85 mg/m^2 i.v. together with leucovorin 400 mg/m^2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 2400 mg/m^2 in 46 hours, every 2 weeks) or mFOLFOX6 plus bevacizumab (Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by oxaliplatin 85 mg/m^2 i.v. together with leucovorin 400 mg/m^2 i.v. in 120 minutes, followed by bolus 5FU 400 mg/m^2, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m^2 in 46 hours, every 2 weeks).
Patients will be evaluated every 8 weeks by MRI or CT scan for disease status. The assigned systemic treatment should be continued for at least 6 months or earlier in case of resectability, progression of disease, unacceptable toxicity, or patient refusal. If after 6 months MDT concludes that the patient is still not resectable, it is highly unlikely that resectability will be achieved at all. Therefore the chemotherapy regimen may be reconsidered after 6 months of treatment. These patients will continue with bevacizumab plus fluoropyrimidine until progression or unacceptable toxicity.
In patients who will become resectable and undergo secondary surgery of liver metastases, the total duration of preoperative and postoperative treatment together should be 6 months. However, in these patients mFOLFOXIRI should not be continued after surgery and replaced by mFOLFOX6. Bevacizumab will continued after surgery for both groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| mFOLFOXIRI+Bev | Experimental | Drug: mFOLFOXIRI regimen, Drug: BevacizumabPatients will receive mFOLFOXIRI plus bevacizumab once every two weeks as the first-line treatment. Drug: mFOLFOXIRI plus Bevacizumab Bevacizumab (5 mg/kg on day 1) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1). A local MDT will assess the efficiency every 4 cycles of the treatment. The maximum period of conversion therapy is 12 cycles. |
| mFOLFOX6+Bev | Active comparator | Drug: mFOLFOX regimen, Drug: BevacizumabPatients will receive mFOLFOX6 plus bevacizumab once every two weeks as the first-line treatment. Drug: mFOLFOX6 Plus Bevacizumab mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1). A local MDT will assess the efficiency every 4 cycles of the treatment. The maximum period of conversion therapy is 12 cycles. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histological proof of colorectal adenocarcinoma;
- Age ≥ 18 years and ≤75 years;
- Simultaneous liver-limited metastases;
- Initially unresectable liver metastases determined by a local MDT;
- RAS mutation and BRAF V600E wild-type;
Key exclusion criteria (12 listed)
- Previous systemic treatment for metastatic disease;
- Previous surgery for metastatic disease;
- Extrahepatic metastases;
- Unresectable primary tumor;
- Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation;
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 |
|---|---|---|
| mFOLFOXIRI regimenoxaliplatin 85 mg/m2, irinotecan 165 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1 | Drug | mFOLFOXIRI+Bev |
| mFOLFOX regimenoxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1 | Drug | mFOLFOX6+Bev |
| Bevacizumab5 mg/kg on day 1 | Drug | mFOLFOX6+Bev, mFOLFOXIRI+Bev |
Primary outcome
conversion resection rate
Time frame: up to 6 months
R0 resection rate upon conversion treatment with chemotherapy plus bevacizumab
8 secondary outcomes
Overall survival (OS)
Time frame: up to 2 years
Progression-free survival (PFS)
Time frame: up to 2 years
Toxicity (AE)
Time frame: up to 6 months
postoperative complication
Time frame: After surgery during one month
overall response
Time frame: up to 6 months
proportion of no evidence of disease
Time frame: up to 6 months
Best deepness of response
Time frame: up to 6 months
Early tumor shrinkage
Time frame: at 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 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.
Jianmin Xu, MD, Ph.D. principal investigator
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing mFOLFOXIRI regimen, mFOLFOX regimen and Bevacizumab in people with Colorectal Carcinoma and Liver Metastases, run by Fudan University at 1 site in China.
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 12 inclusion and 12 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 27 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Jianmin Xu, MD, Ph.D. (021-64041990, xujmin@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
conversion resection rate (time frame: up to 6 months). 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 27 Sep 2021.