Colorectal Liver Metastasis (CRLM)Phase 2NCT06988852
FOLFOX-HAIC as Conversion Treatment for Initially Unresectable Colorectal Liver Metastasis
A Phase 2 study testing FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]), hepatic arterial infusion chemotherapy (HAIC) and Bevacizumab in people with Colorectal Liver Metastasis (CRLM), run by Tongji Hospital at 1 site in China.
Trial summary
Try FOLFOX-HAIC combining bevacizumab or cetuximab for initially unresectable colorectal liver metastasis patients to increase the conversion to resection rate to improve long-term survival outcomes Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Liver Metastasis (CRLM)
- What is being tested?
- FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]), hepatic arterial infusion chemotherapy (HAIC) and Bevacizumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2023to 31 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18-75 years
- no history of other malignant diseases
- refuse or progress in prior systemic treatment
- diagnosed as CRLM confirmed by pathology, in spite of whether the primary tumor had been resected
- at least one lesion in the liver could be measured
- left ventricular ejection ≥45%, forced expiratory volume in one second/forced vital capacity≥60% and Eastern Cooperative Oncology Group (ECOG) score of 0-1
- Child-Pugh class A
- adequate organ function, i.e.: white blood cell (WBC) ≥3.0×109/L, neutrophils ≥1.5×109/L, platelet (PLT) ≥75×109/L, total bilirubin ≤30μmol/L, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤200U/L, creatinine ≤150μmol/L
Who cannot join
- extra-hepatic metastasis verified by medical imaging
- unable to tolerate chemotherapy, anesthesia or surgery
- allergy or previous intolerable to any agent of oxaliplatin, leucovorin, 5-Fu, bevacizumab or cetuximab
- tumor spread in abdomen
- cerebral infarction, cerebral hemorrhage, gastrointestinal hemorrhage/perforation within 6 months, coagulation disorders and gastrointestinal ulcer
- primary tumor may not be completely resected
- prior treatment of CRLM with resection, ablation or radiation
- incomplete clinical or follow-up data
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430030
Liao Wei, 8615527803087, 1009739952@qq.com
About this study
Official title: Conversion Treatment With Hepatic Arterial Infusion of Oxaliplatin, Leucovorin and Fluorouracil Plus Intravenous Bevacizumab or Cetuximab for Initially Unresectable Colorectal Liver Metastasis: A Prospective Study
Try FOLFOX-HAIC combining bevacizumab or cetuximab for initially unresectable colorectal liver metastasis patients to increase the conversion to resection rate to improve long-term survival outcomes
Read the detailed description
Colorectal cancer (CRC) was a common malignancy. Approximately 50% CRC patients would develop either synchronous or metachronous liver metastasis, which served as the leading cause of death in CRC, during the course of their diseases. Complete resection of all liver metastases is a major contributor to long-term survival with a median OS of 35 months, while it is just 20-24 months in modern chemotherapy. However,80%-90% colorectal liver metastasis (CRLM) patients present with initially unresectable diseases and the median OS in untreated patients is only 7.5 months. Liver transplantation achieves a 5-year OS rate of 56% compared to the rate of 9% for systemic chemotherapy, organ shortage and high cost limit its popularization. Conversion treatment refers to applying local and/or systemic treatment for IU-CRLM to eliminate technical or biologic unresectable factors to gain potential resectable states and is associated with a 5-year OS rate of 30%-61% in successful patients, which is non-inferior to those who are initially resectable. However, the conversion to resection rates (CTRRs) with negative margin vary from 1.7% to 66% depending on treatment regimens. So, promoting the conversion ability is the only way to improve long-term survival.
The systemic conversion treatment includes systemic chemotherapy and target agents. It shows high adverse event (AE) rates in practice and the CTRRs varies from 1.7% to 49%, which is unsatisfactory. The locoregional conversion treatment, such as hepatic arterial infusion chemotherapy (HAIC), transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and so on, is only suitable for liver-only metastases. For the reason of CRLM deriving predominant blood supply from hepatic artery while liver parenchyma mainly from portal vein, transarterial interventional therapy may not only improve the CTRRs but also reduce AE rates. It's a pity that the CTRRs in TACE or TARE only range from 7% to 10%. HAIC achieves 17.8%-66% CTRRs depending on different drug regimens. Target agents indeed increases the CTTRs in systemic chemotherapy, but bevacizumab doesn't increases it in FUDR-HAIC and brings unexpectedly biliary toxicity. However, in unresectable hepatocellular carcinoma (uHCC), FOLFOX-HAIC combining with Sintilimab® and bevacizumab achieved a CTRR of 48.2% and no biliary toxicity event occurred. Another study, oxaliplatin-HAIC with systemic chemotherapy plus cetuximab achieved an impressive CTTR of 66% but was only suitable for patients without mutational RAS. Maybe a new regimen, oxaliplatin-based complete arterial infusion regimen combining with bevacizumab or cetuximab for IU-CRLM could achieve a milestone outcome, but no literature had reported it.
In this study, we establish a prospective and consecutive IU-CRLM patient cohort treated with FOLFOX-HAIC combining with bevacizumab or cetuximab to evaluate the CTRR, tumor response, safety and long-term oncological outcomes.
- Conditions
- Colorectal Liver Metastasis (CRLM)
- Being tested
- FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]), hepatic arterial infusion chemotherapy (HAIC), Bevacizumab, Cetuximab (Erbitux), liver resection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])Combination product
The procedures of FOLFOX-HAIC were as follows: 1) a 5 French sheath was inserted into the femoral artery by Seldinger technique, then a 3.5 French catheter entered the coeliac trunk and superior mesenteric artery to assess the feeding arteries of tumors and identify any extra-collateral vessels which may cause drug leakage. These vessels would be embolized with gelatin sponge particles or metallic coils if necessary. A 2.7 French microcatheter was selectively inserted into the left/right/proper hepatic artery then patients were transferred to inpatient ward to start chemotherapy drug infusion. The FOLFOX regimen involving oxaliplatin (130mg/m2, day 1, 0-2h), leucovorin (400 mg/m2, day 1, 2-3h), 5-Fu (400mg/m2, day 1, bolus at 3h, then 2400 mg/m2, day 1-3, 3-49h), was administered via the microcatheter. The microcatheter and sheath were removed after HAIC finished. We didn't implanted port catheter system and repeated percutaneous femoral artery puncture and catheterization once every 3
hepatic arterial infusion chemotherapy (HAIC)Procedure or surgery
The procedures of FOLFOX-HAIC were as follows: 1) a 5 French sheath was inserted into the femoral artery by Seldinger technique, then a 3.5 French catheter entered the coeliac trunk and superior mesenteric artery to assess the feeding arteries of tumors and identify any extra-collateral vessels which may cause drug leakage. These vessels would be embolized with gelatin sponge particles or metallic coils if necessary. A 2.7 French microcatheter was selectively inserted into the left/right/proper hepatic artery then patients were transferred to inpatient ward to start chemotherapy drug infusion.
BevacizumabDrug
We would inject bevacizumab at the dose of 7.5mg/kg once every 3 weeks if the primary tumors located from right-side to splenic flexure colon or the genotype of RAS or RAF was mutational.
Cetuximab (Erbitux)Drug
We would inject cetuximab at an initial dose of 400mg/m2 and maintained a dose of 250mg/m2 once every week if we didn't choose bevacizumab.
liver resectionProcedure or surgery
If patients reached potential resectable state, we would perform liver resection.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | Patients in the treatment group would undergo FOLFOX-HAIC combining Bevacizumab or Cetuximab Receives: Combination Product: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Procedure: hepatic arterial infusion chemotherapy (HAIC); Drug: Bevacizumab; Drug: Cetuximab (Erbitux); Procedure: liver resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
conversion to resection rate
conversion to resection rate: the number of patients underwent liver resection/total patients underwent FOLFOX-HAIC combining with target agents
Measured: 180 days
Secondary outcomes (2)
drug treatment safety assessment
Any adverse event during treatment that is incompatible with the therapeutic purpose of the medication. The incidence and severity of adverse events and serious adverse events as assessed according to CTCAE v5.0.
Measured: Baseline up to study termination, assessed up to 12 months.
objective response rate
Objective response rate (ORR) was defined as the sum of cases with complete response (CR) and partial response (PR) which assessed by the RECIST 1.1 criteria.
Measured: From the time of enrollment until disease progression, death, or the end of the study, assessed up to 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2025
- Study start1 May 2023
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal Liver Metastasis (CRLM)Studies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chen Xiaoping, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06988852
- Sponsor's protocol ID
- CHALLENGE-A1
- Status last verified
- May 2025
- First submitted
- 4 May 2025
- Last updated
- 25 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Liao W, Cheng Q, Chen L, Zhang B, Ding Z, Mu K, Xu A, Song J, Dong W, Zhang M, Chen J, Huang Z, Chen X, Zhu P, Zhang B. Conversion treatment with hepatic arterial infusion of oxaliplatin, leucovorin and fluorouracil plus intravenous bevacizumab or cetuximab for initially unresectable colorectal liver metastasis: A prospective study. Cancer Treat Res Commun. 2026;47:101153. doi: 10.1016/j.ctarc.2026.101153. Epub 2026 Feb 24.
PubMed 41775173
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Conversion Treatment With Hepatic Arterial Infusion of Oxaliplatin, Leucovorin and Fluorouracil Plus Intravenous Bevacizumab or Cetuximab for Initially Unresectable Colorectal Liver Metastasis: A Prospective Study
- ClinicalTrials.gov ID
- NCT06988852
- Acronym / sponsor ID
- CHALLENGE-A1
- Conditions
- Colorectal Liver Metastasis (CRLM)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Study start
- 1 May 2023 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 25 May 2025 (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.
Try FOLFOX-HAIC combining bevacizumab or cetuximab for initially unresectable colorectal liver metastasis patients to increase the conversion to resection rate to improve long-term survival outcomes
Detailed description
Colorectal cancer (CRC) was a common malignancy. Approximately 50% CRC patients would develop either synchronous or metachronous liver metastasis, which served as the leading cause of death in CRC, during the course of their diseases. Complete resection of all liver metastases is a major contributor to long-term survival with a median OS of 35 months, while it is just 20-24 months in modern chemotherapy. However,80%-90% colorectal liver metastasis (CRLM) patients present with initially unresectable diseases and the median OS in untreated patients is only 7.5 months. Liver transplantation achieves a 5-year OS rate of 56% compared to the rate of 9% for systemic chemotherapy, organ shortage and high cost limit its popularization. Conversion treatment refers to applying local and/or systemic treatment for IU-CRLM to eliminate technical or biologic unresectable factors to gain potential resectable states and is associated with a 5-year OS rate of 30%-61% in successful patients, which is non-inferior to those who are initially resectable. However, the conversion to resection rates (CTRRs) with negative margin vary from 1.7% to 66% depending on treatment regimens. So, promoting the conversion ability is the only way to improve long-term survival.
The systemic conversion treatment includes systemic chemotherapy and target agents. It shows high adverse event (AE) rates in practice and the CTRRs varies from 1.7% to 49%, which is unsatisfactory. The locoregional conversion treatment, such as hepatic arterial infusion chemotherapy (HAIC), transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and so on, is only suitable for liver-only metastases. For the reason of CRLM deriving predominant blood supply from hepatic artery while liver parenchyma mainly from portal vein, transarterial interventional therapy may not only improve the CTRRs but also reduce AE rates. It's a pity that the CTRRs in TACE or TARE only range from 7% to 10%. HAIC achieves 17.8%-66% CTRRs depending on different drug regimens. Target agents indeed increases the CTTRs in systemic chemotherapy, but bevacizumab doesn't increases it in FUDR-HAIC and brings unexpectedly biliary toxicity. However, in unresectable hepatocellular carcinoma (uHCC), FOLFOX-HAIC combining with Sintilimab® and bevacizumab achieved a CTRR of 48.2% and no biliary toxicity event occurred. Another study, oxaliplatin-HAIC with systemic chemotherapy plus cetuximab achieved an impressive CTTR of 66% but was only suitable for patients without mutational RAS. Maybe a new regimen, oxaliplatin-based complete arterial infusion regimen combining with bevacizumab or cetuximab for IU-CRLM could achieve a milestone outcome, but no literature had reported it.
In this study, we establish a prospective and consecutive IU-CRLM patient cohort treated with FOLFOX-HAIC combining with bevacizumab or cetuximab to evaluate the CTRR, tumor response, safety and long-term oncological outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Combination Product: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]), Procedure: hepatic arterial infusion chemotherapy (HAIC), Drug: Bevacizumab, Drug: Cetuximab (Erbitux), Procedure: liver resectionPatients in the treatment group would undergo FOLFOX-HAIC combining Bevacizumab or Cetuximab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- age 18-75 years
- no history of other malignant diseases
- refuse or progress in prior systemic treatment
- diagnosed as CRLM confirmed by pathology, in spite of whether the primary tumor had been resected
- at least one lesion in the liver could be measured
Key exclusion criteria (8 listed)
- extra-hepatic metastasis verified by medical imaging
- unable to tolerate chemotherapy, anesthesia or surgery
- allergy or previous intolerable to any agent of oxaliplatin, leucovorin, 5-Fu, bevacizumab or cetuximab
- tumor spread in abdomen
- cerebral infarction, cerebral hemorrhage, gastrointestinal hemorrhage/perforation within 6 months, coagulation disorders and gastrointestinal ulcer
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 |
|---|---|---|
| FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])The procedures of FOLFOX-HAIC were as follows: 1) a 5 French sheath was inserted into the femoral artery by Seldinger technique, then a 3.5 French catheter entered the coeliac trunk and superior mesenteric artery to assess the feeding arteries of tumors and identify any extra-collateral vessels which may cause drug leakage. These vessels would be embolized with gelatin sponge particles or metallic coils if necessary. A 2.7 French microcatheter was selectively inserted into the left/right/proper hepatic artery then patients were transferred to inpatient ward to start chemotherapy drug infusion. The FOLFOX regimen involving oxaliplatin (130mg/m2, day 1, 0-2h), leucovorin (400 mg/m2, day 1, 2-3h), 5-Fu (400mg/m2, day 1, bolus at 3h, then 2400 mg/m2, day 1-3, 3-49h), was administered via the microcatheter. The microcatheter and sheath were removed after HAIC finished. We didn't implanted port catheter system and repeated percutaneous femoral artery puncture and catheterization once every 3 | Combination product | Treatment group |
| hepatic arterial infusion chemotherapy (HAIC)The procedures of FOLFOX-HAIC were as follows: 1) a 5 French sheath was inserted into the femoral artery by Seldinger technique, then a 3.5 French catheter entered the coeliac trunk and superior mesenteric artery to assess the feeding arteries of tumors and identify any extra-collateral vessels which may cause drug leakage. These vessels would be embolized with gelatin sponge particles or metallic coils if necessary. A 2.7 French microcatheter was selectively inserted into the left/right/proper hepatic artery then patients were transferred to inpatient ward to start chemotherapy drug infusion. | Procedure or surgery | Treatment group |
| BevacizumabWe would inject bevacizumab at the dose of 7.5mg/kg once every 3 weeks if the primary tumors located from right-side to splenic flexure colon or the genotype of RAS or RAF was mutational. | Drug | Treatment group |
| Cetuximab (Erbitux)We would inject cetuximab at an initial dose of 400mg/m2 and maintained a dose of 250mg/m2 once every week if we didn't choose bevacizumab. | Drug | Treatment group |
| liver resectionIf patients reached potential resectable state, we would perform liver resection. | Procedure or surgery | Treatment group |
Primary outcome
conversion to resection rate
Time frame: 180 days
conversion to resection rate: the number of patients underwent liver resection/total patients underwent FOLFOX-HAIC combining with target agents
2 secondary outcomes
drug treatment safety assessment
Time frame: Baseline up to study termination, assessed up to 12 months.
objective response rate
Time frame: From the time of enrollment until disease progression, death, or the end of the study, assessed up to 12 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Derived from this study: PubMed 41775173Liao W, Cheng Q, Chen L, Zhang B, Ding Z, Mu K, Xu A, Song J, Dong W, Zhang M, Chen J, Huang Z, Chen X, Zhu P, Zhang B. Conversion treatment with hepatic arterial infusion of oxaliplatin, leucovorin and fluorouracil plus intravenous bevacizumab or cetuximab for initially unresectable colorectal liver metastasis: A prospective study. Cancer Treat Res Commun. 2026;47:101153. doi: 10.1016/j.ctarc.2026.101153. Epub 2026 Feb 24.
- Individual participant dataSharing planned: No
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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.
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 FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]), hepatic arterial infusion chemotherapy (HAIC) and Bevacizumab in people with Colorectal Liver Metastasis (CRLM), run by Tongji Hospital 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 8 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 25 May 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhang Bi Xiang (862783663400, bixiangzhang@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
conversion to resection rate (time frame: 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06988852, which also lists 1 linked publication.
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 25 May 2025; AzTrials last refreshed its copy on 26 Oct 2026.