Metastatic Colorectal CancerPhase 2FORBESNCT02350530
FOLFOXIRI With or Without Bevacizumab as First-line Treatment for Unresectable Liver-only Metastatic Colorectal Cancer Patients With RAS Mutation-type
A Phase 2 study testing FOLFOXIRI + Bevacizumab and FOLFOXIRI in people with Metastatic Colorectal Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
BACKGROUND: For patients with liver-limited metastatic colorectal cancer (mCRC), complete resection of liver metastases is the only potentially curative treatment. The current goal of medical treatment for colorectal cancer with initially unresectable liver metastases is to maximize the rate of secondary resection and… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- FOLFOXIRI + Bevacizumab and FOLFOXIRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2015to 1 Jan 2020
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent
- Histological or cytological documentation of adenocarcinoma of the colon or rectum.
- Male or female subjects > 18 years < 70 of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- There must be documentation by CT scan, MRI, or intraoperative palpation that the patient has evidence of metastases confined to the liver.
- The liver metastases must have been assessed by multidisciplinary team including hepatic surgeon approved to participate in the study to be unresectable based on at least one of the four criteria: 1. All of the liver metastases can not be completed resected with negative margins; 2. No ability to preservation of two contiguous hepatic segments; 3. No ability to preservation of adequate vascular inflow and outflow as well as biliary drainage; 4. Complete resection would require greater than 70% of the liver parenchyma to be removed.
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- The colorectal primary tumor or metastatic tumor must be determined to be KRAS (exon 2 at codon 12 and 13; exon 3 at codon 59 and 61; exon 4 at codon 117 and 146) or NRAS (exon 2 at codon 12 and 13; exon 3 at codon 59 and 61; exon 4 at codon 117 and 146) mutation-type.
- Primary tumor and regional nodes were resected with clear surgical margins or; unresected primary tumor with plan to radical resect the primary tumor.
- No previous any systemic anticancer therapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago).
- Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Hemoglobin (Hb) ≥ 90g/ L, absolute neutrophil count (ANC) ≥ 1.5×109/ L, platelet count ≥ 100×109/ L; Total bilirubin ≤ 1.5×the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 ×ULN; Serum creatinine ≤1.5×the ULN.
Who cannot join
- Any evidence of extrahepatic metastases, lymph node (including portal lymph nodes) metastases and primary tumor recurrence.
- Previous hepatic resection and/or ablation, hepatic arterial infusion therapy, radiation therapy to the liver.
- Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
- Heart failure grade III/IV (NYHA-classification).
- Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
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- Subjects with known allergy to the study drugs or to any of its excipients.
- Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
- Breast- feeding or pregnant women
- Lack of effective contraception.
Trial locations and contacts
1 site in 1 country.
China1 site
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510655
About this study
Official title: A Phase II Study to Evaluate the Surgical Conversion Rate in Patients With RAS Mutation-type Receiving FOLFOXIRI +/- Bevacizumab for Unresectable Colorectal Liver-Limited Metastases
BACKGROUND:
For patients with liver-limited metastatic colorectal cancer (mCRC), complete resection of liver metastases is the only potentially curative treatment. The current goal of medical treatment for colorectal cancer with initially unresectable liver metastases is to maximize the rate of secondary resection and prolong overall survival (OS). A strong correlation was found between response rate and secondary resection rate of metastases, and the triple drugs combination of infusional 5-fluorouracil/leucovorin (5-FU/LV), irinotecan, and oxaliplatin (FOLFOXIRI) was recommended can be used in selected patients with potentially resectable metastases in order to improve response rate and make resection more possible. The addition of a anti-VEGFs monoclonal antibody such as bevacizumab to chemotherapy has been shown to increase response rate, resection rate and improve OS in the first-line treatment of mCRC patients. The efficacy and safety of bevacizumab in addition to triplet drugs were previously tested in OLIVIA trial, the resection rate of liver metastases of 49% was reported, and the response rate was 81%; most common grade 3-4 adverse events was neutropenia. On the basis of such promising results, we conducted the present randomized study to explore whether FOLFOXIRI plus bevacizumab compared with FOLFOXIRI alone as first-line treatment could improve radical resectability in patients with RAS mutation-type, unresectable liver-only metastatic colorectal cancer.
Read more
OBJECTIVE:
The primary objective of the FOBULM study is to evaluate the efficacy of FOLFOXIRI plus bevacizumab compared to FOLFOXIRI alone in patients with initially unresectable liver-limited RAS mutation-type mCRC.
Secondary objectives are safety and tolerability of the treatment, efficacy in terms of objective response rate (ORR), OS, progression free survival (PFS), quality of life and an assessment of biomarkers for predictive response and prognosis.
Read the detailed description
OVERVIEW OF TRIAL DESIGN
This FOCULM trial is a a two-arm, multicenter, open labelled, prospective, randomized phase II studies. Eligible patients with initially unresectable liver-limited mCRC will be randomised 1:1 to receive either FOLFOXIRI plus bevacizumab or FOLFOXIRI alone.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- FOLFOXIRI + Bevacizumab, FOLFOXIRI
- Keywords
- Colorectal cancer, Metastatic colorectal cancer, Liver metastases, Liver resection, Liver ablation, Conversion therapy, FOLFOXIRI, Oxaliplatin, Irinotecan, Fluorouracil, Bevacizumab, RAS mutation
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOXIRI + BevacizumabDrug
Also called Bevacizumab, Irinotecan, Oxaliplatin, 5-Fluorouracil
Bevacizumab 5mg/kg + irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles
FOLFOXIRIDrug
Also called Irinotecan, Oxaliplatin, 5-Fluorouracil
Irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles
| Study group | Role | What they receive |
|---|---|---|
| A (FOLFOXIRI + Bevacizumab) | Experimental | FOLFOXIRI + Bevacizumab Receives: Drug: FOLFOXIRI + Bevacizumab |
| B (FOLFOXIRI) | Active comparator | FOLFOXIRI Receives: Drug: FOLFOXIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
The conversion rate of liver metastases
Defined as the proportion of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be radical resected with or without ablation with no postoperative evidence of residual malignant disease.
Measured: 8 months
Secondary outcomes (5)
Toxicity assessed using the NCI common toxicity criteria, version 4.0.
The grade of toxicity will be assessed using the NCI common toxicity criteria, version 4.0.
Measured: 8 months
Response rate
CR + PR rate will be assessed according to the RECIST version 1.1 guidelines.
Measured: 8 months
Overall survival time
Estimated from the date of randomization to death from any cause.
Measured: 5 years
Progression free survival
Time measured from the day of randomization to the date of first documented progression, or death from any cause.
Measured: 2 years
Quality of life (QLQ C30)
Scores according to EORTC QLQ-C30 scoring manual
Measured: Every 2 weeks after the first treatment until 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2015 (estimated)
- Study start1 Jan 2015
- Primary completion1 Jan 2018
- Study completion1 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanhong Deng, Sun Yat-sen University
- Investigators
- Yanhong Deng, M.D., Principal investigator, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02350530
- Sponsor's protocol ID
- GIHSYSU09
- Acronym
- FORBES
- Status last verified
- May 2026
- First submitted
- 24 Jan 2015
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Evaluate the Surgical Conversion Rate in Patients With RAS Mutation-type Receiving FOLFOXIRI +/- Bevacizumab for Unresectable Colorectal Liver-Limited Metastases
- ClinicalTrials.gov ID
- NCT02350530
- Acronym / sponsor ID
- FORBES / GIHSYSU09
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Colorectal cancer, Metastatic colorectal cancer, Liver metastases, Liver resection, Liver ablation, Conversion therapy, FOLFOXIRI, Oxaliplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Jan 2015 (actual)
- Primary completion
- 1 Jan 2018 (actual)
- Study completion
- 1 Jan 2020 (actual)
- First posted
- 29 Jan 2015 (estimated)
- 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.
BACKGROUND:
For patients with liver-limited metastatic colorectal cancer (mCRC), complete resection of liver metastases is the only potentially curative treatment. The current goal of medical treatment for colorectal cancer with initially unresectable liver metastases is to maximize the rate of secondary resection and prolong overall survival (OS). A strong correlation was found between response rate and secondary resection rate of metastases, and the triple drugs combination of infusional 5-fluorouracil/leucovorin (5-FU/LV), irinotecan, and oxaliplatin (FOLFOXIRI) was recommended can be used in selected patients with potentially resectable metastases in order to improve response rate and make resection more possible. The addition of a anti-VEGFs monoclonal antibody such as bevacizumab to chemotherapy has been shown to increase response rate, resection rate and improve OS in the first-line treatment of mCRC patients. The efficacy and safety of bevacizumab in addition to triplet drugs were previously tested in OLIVIA trial, the resection rate of liver metastases of 49% was reported, and the response rate was 81%; most common grade 3-4 adverse events was neutropenia. On the basis of such promising results, we conducted the present randomized study to explore whether FOLFOXIRI plus bevacizumab compared with FOLFOXIRI alone as first-line treatment could improve radical resectability in patients with RAS mutation-type, unresectable liver-only metastatic colorectal cancer.
OBJECTIVE:
The primary objective of the FOBULM study is to evaluate the efficacy of FOLFOXIRI plus bevacizumab compared to FOLFOXIRI alone in patients with initially unresectable liver-limited RAS mutation-type mCRC.
Secondary objectives are safety and tolerability of the treatment, efficacy in terms of objective response rate (ORR), OS, progression free survival (PFS), quality of life and an assessment of biomarkers for predictive response and prognosis.
Detailed description
OVERVIEW OF TRIAL DESIGN
This FOCULM trial is a a two-arm, multicenter, open labelled, prospective, randomized phase II studies. Eligible patients with initially unresectable liver-limited mCRC will be randomised 1:1 to receive either FOLFOXIRI plus bevacizumab or FOLFOXIRI alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A (FOLFOXIRI + Bevacizumab) | Experimental | Drug: FOLFOXIRI + BevacizumabFOLFOXIRI + Bevacizumab |
| B (FOLFOXIRI) | Active comparator | Drug: FOLFOXIRIFOLFOXIRI |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Willing and able to provide written informed consent
- Histological or cytological documentation of adenocarcinoma of the colon or rectum.
- Male or female subjects > 18 years < 70 of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- There must be documentation by CT scan, MRI, or intraoperative palpation that the patient has evidence of metastases confined to the liver.
Key exclusion criteria (10 listed)
- Any evidence of extrahepatic metastases, lymph node (including portal lymph nodes) metastases and primary tumor recurrence.
- Previous hepatic resection and/or ablation, hepatic arterial infusion therapy, radiation therapy to the liver.
- Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
- Heart failure grade III/IV (NYHA-classification).
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 |
|---|---|---|
| FOLFOXIRI + BevacizumabAlso: Bevacizumab, Irinotecan, Oxaliplatin, 5-FluorouracilBevacizumab 5mg/kg + irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles | Drug | A (FOLFOXIRI + Bevacizumab) |
| FOLFOXIRIAlso: Irinotecan, Oxaliplatin, 5-FluorouracilIrinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles | Drug | B (FOLFOXIRI) |
Primary outcome
The conversion rate of liver metastases
Time frame: 8 months
Defined as the proportion of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be radical resected with or without ablation with no postoperative evidence of residual malignant disease.
5 secondary outcomes
Toxicity assessed using the NCI common toxicity criteria, version 4.0.
Time frame: 8 months
Response rate
Time frame: 8 months
Overall survival time
Time frame: 5 years
Progression free survival
Time frame: 2 years
Quality of life (QLQ C30)
Time frame: Every 2 weeks after the first treatment until 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
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CRC
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.
Yanhong Deng, M.D. principal investigator
Sixth Affiliated Hospital, Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FOLFOXIRI + Bevacizumab and FOLFOXIRI in people with Metastatic Colorectal Cancer, run by Sun Yat-sen 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 10 inclusion and 10 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: finished, as of the sponsor's last update on 22 May 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The conversion rate of liver metastases (time frame: 8 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 22 May 2026.