Hepatocellular CarcinomaPhase 2NCT02426450
RFA Combined With Oxaliplatin + 5-FluoroUracil/LeucoVorin (5-FU/LV) (FOLFOX4) for Recurrent HCC
A Phase 2 study testing RFA, Oxaliplatin and 5-Fluorouracil/Leucovorin in people with Hepatocellular Carcinoma, run by Sun Yat-sen University at 1 site in China.
Trial summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Partial hepatectomy and liver transplantation are considered to be standard curative therapies for HCC. When surgery is not possible, percutaneous ablation is usually considered to be alternative treatments for HCC. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- RFA, Oxaliplatin and 5-Fluorouracil/Leucovorin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteChina
- Study dates
- Apr 2015to Apr 2017
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age 18 - 75 years;
- recurrence of HCC 12 months after initial hepatectomy;
- no other treatment received except for the initial hepatectomy;
- Single tumor≤5cm in diameter; or 2-3 lesions each ≤ 3.0 cm
- lesions visible on ultrasound and with an acceptable and safe path between the lesion and the skin as shown on ultrasound;
- no severe coagulation disorders (prothrombin activity < 40% or a platelet count of < 40,000 / mm3;
- Eastern Co-operative Oncology Group performance(ECOG) status 0 -1
Who cannot join
- severe coagulation disorders (prothrombin activity <40% or a platelet count of <40,000 / mm3);
- Child-Pugh class C liver cirrhosis or evidence of hepatic decompensation including ascites, esophageal or gastric variceal bleeding, or hepatic encephalopathy;
- Documented allergy to platinum compound or to other study drugs; Any previous oxaliplatin or doxorubicin treatment, except adjuvant treatment more than 12 months before the randomization.
- Previous or concurrent cancer that is distinct in primary site or histology from HCC
- History of cardiac disease congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is permitted); cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers, calcium channel blocker or digoxin; uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of 3 antihypertensive drugs).
- Active clinically serious infections (> grade 2 National Cancer Institute [NCI]- Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) contraindications to carboplatin, epirubicin, mitomycin, lipiodol;
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- Pregnant or breast-feeding patients;
- contraindications to RFA；
- Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study;
- Known history of human immunodeficiency virus (HIV) infection
- Patients concomitantly receiving any other anti-cancer therapy, including interferon-α and herbal medicine which was approved by local authority to be used as "anti-cancer" medicine, except radiotherapy to non-target lesion (bone metastasis, etc)
- Do not give written informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: RFA Combined With Oxaliplatin + 5-FluoroUracil/LeucoVorin (5-FU/LV) (FOLFOX4) for Recurrent HCC:an Open Lable, Single-arm, Prospective Study
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Partial hepatectomy and liver transplantation are considered to be standard curative therapies for HCC. When surgery is not possible, percutaneous ablation is usually considered to be alternative treatments for HCC. Recurrence is the most frequent serious adverse event observed during the follow-up of HCC patients treated for cure. Repeat hepatectomy is an effective treatment for HCC recurrence, with a 5-year survival rate of 19.4 to 56%. Unfortunately, repeat hepatectomy can be performed only in a small proportion of patients with HCC recurrence (10.4 to 31%), either because of the poor functional liver reserve or because of widespread recurrence. Radiofrequency ablation has been considered to be one of the most effective percutaneous ablations for early-stage HCC in patients with or without surgical prospects. Studies using RFA to treat HCC recurrence after hepatectomy have reported a 3-year survival rate of 62% to 68%, which is comparable to those achieved by surgery. RFA is particularly suitable to treat HCC recurrence after hepatectomy because these tumors are usually detected when they are small, and because RFA causes the least deterioration of liver function in the patients. However, according to our previous study, investigators found the recurrent rate after RFA was higher than 60%. Systemic chemotherapy is considered to be one of the main treatments for malignant tumors. HCC is known to be highly refractory to conventional systemic chemotherapy because of its heterogeneity and multiple etiologies. Before the advent of the molecular-targeted agent sorafenib, which has subsequently become the standard of care, no standard systemic drug or treatment regimen had shown an obvious survival benefit in HCC. Nowadays, there is no systemic chemotherapy regimen had been definitively recommended as the standard for treating HCC. Clinical activity of several regimens containing oxaliplatin (OXA) in advanced HCC had been demonstrated in phase II studies. In a phase II study of the FOLFOX4 (infusional fluorouracil [FU], leucovorin[LV], and OXA) regimen in Chinese patients with HCC, median overall survival (OS) was 12.4 months, mean time to progression was 2.0 months, and the response rate (RR) was 18.2%. The safety profile was acceptable. Recently, the results of a phase Ⅲ randomize study showed that FOLFOX4 served as palliative chemotherapy can induce higher overall survival, progression-free survival and response rate comparing to doxorubicin in patients with advanced hepatocellular carcinoma from Asia. The safety data was also acceptable. Therefore, investigators considered RFA to be an effective treatment for HCC recurrence after curative treatment. So our hypothesis is that RFA combined with FOLFOX4 can reduce high recurrence rate after RFA for recurrent HCC after hepatectomy. The aim of this open-lable, single prospective study is to evaluate the efficacy and safety of RFA combined with FOLFOX4 systemic chemotherapy for recurrent HCC after partial hepatectomy.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- RFA, Oxaliplatin, 5-Fluorouracil/Leucovorin
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RFAProcedure or surgery
RFA:
RFA was performed by using a commercially available system (RF 2000; Radio-Therapeutics Mountain View, CA), and a needle electrode with a 15 Ga insulated cannula with 10 hook-shaped expandable electrode tines with a diameter of 3.5 cm at expansion (LeVeen; RadioTherapeutics).
OxaliplatinDrug
4 weeks after RFA; Drug: Oxaliplatin Day 1: Oxaliplatin 85mg/m² 2h IV infusion. Repeated every 2 weeks
5-Fluorouracil/LeucovorinDrug
4 weeks after RFA; Drug: 5-Fluorouracil/Leucovorin Day 1, after Oxaliplatin 85mg/m² 2h IV infusion: Leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m2 22h IV infusion.
Day 2: Leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m² 22h IV infusion.
Repeated every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| RFA+FOLFOX4 | Experimental | RFA:
RFA was performed by using a commercially available system (RF 2000; Radio-Therapeutics Mountain View, CA), and a needle electrode with a 15 Ga insulated cannula with 10 hook-shaped expandable electrode tines with a diameter of 3.5 cm at expansion (LeVeen; RadioTherapeutics).
Oxaliplatin + 5-Fluorouracil/Leucovorin:
4 weeks after RFA; Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin Day 1: Oxaliplatin 85mg/m² 2h IV infusion, leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m2 22h IV infusion.
Day 2: Leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m² 22h IV infusion.
Repeated every 2 weeks Receives: Procedure: RFA; Drug: Oxaliplatin; Drug: 5-Fluorouracil/Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence rate
Measured: 2 years
Safety and Tolerability
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: 2 years
Secondary outcomes (2)
Recurrence-free survival
Measured: 2 years
Overall survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionOct 2015 (estimated)
- Study completionApr 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhen-Wei Peng, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02426450
- Sponsor's protocol ID
- HCC001
- Status last verified
- Apr 2015
- First submitted
- 16 Apr 2015
- Last updated
- 27 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. doi: 10.1200/JCO.2012.44.5643. Epub 2013 Aug 26.
PubMed 23980077Peng ZW, Zhang YJ, Chen MS, Xu L, Liang HH, Lin XJ, Guo RP, Zhang YQ, Lau WY. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol. 2013 Feb 1;31(4):426-32. doi: 10.1200/JCO.2012.42.9936. Epub 2012 Dec 26.
PubMed 23269991Peng ZW, Zhang YJ, Liang HH, Lin XJ, Guo RP, Chen MS. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology. 2012 Feb;262(2):689-700. doi: 10.1148/radiol.11110637. Epub 2011 Dec 12.
PubMed 22157201
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RFA Combined With Oxaliplatin + 5-FluoroUracil/LeucoVorin (5-FU/LV) (FOLFOX4) for Recurrent HCC:an Open Lable, Single-arm, Prospective Study
- ClinicalTrials.gov ID
- NCT02426450
- Acronym / sponsor ID
- HCC001
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Apr 2017 (estimated)
- First posted
- 27 Apr 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.
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Partial hepatectomy and liver transplantation are considered to be standard curative therapies for HCC. When surgery is not possible, percutaneous ablation is usually considered to be alternative treatments for HCC. Recurrence is the most frequent serious adverse event observed during the follow-up of HCC patients treated for cure. Repeat hepatectomy is an effective treatment for HCC recurrence, with a 5-year survival rate of 19.4 to 56%. Unfortunately, repeat hepatectomy can be performed only in a small proportion of patients with HCC recurrence (10.4 to 31%), either because of the poor functional liver reserve or because of widespread recurrence. Radiofrequency ablation has been considered to be one of the most effective percutaneous ablations for early-stage HCC in patients with or without surgical prospects. Studies using RFA to treat HCC recurrence after hepatectomy have reported a 3-year survival rate of 62% to 68%, which is comparable to those achieved by surgery. RFA is particularly suitable to treat HCC recurrence after hepatectomy because these tumors are usually detected when they are small, and because RFA causes the least deterioration of liver function in the patients. However, according to our previous study, investigators found the recurrent rate after RFA was higher than 60%. Systemic chemotherapy is considered to be one of the main treatments for malignant tumors. HCC is known to be highly refractory to conventional systemic chemotherapy because of its heterogeneity and multiple etiologies. Before the advent of the molecular-targeted agent sorafenib, which has subsequently become the standard of care, no standard systemic drug or treatment regimen had shown an obvious survival benefit in HCC. Nowadays, there is no systemic chemotherapy regimen had been definitively recommended as the standard for treating HCC. Clinical activity of several regimens containing oxaliplatin (OXA) in advanced HCC had been demonstrated in phase II studies. In a phase II study of the FOLFOX4 (infusional fluorouracil [FU], leucovorin[LV], and OXA) regimen in Chinese patients with HCC, median overall survival (OS) was 12.4 months, mean time to progression was 2.0 months, and the response rate (RR) was 18.2%. The safety profile was acceptable. Recently, the results of a phase Ⅲ randomize study showed that FOLFOX4 served as palliative chemotherapy can induce higher overall survival, progression-free survival and response rate comparing to doxorubicin in patients with advanced hepatocellular carcinoma from Asia. The safety data was also acceptable. Therefore, investigators considered RFA to be an effective treatment for HCC recurrence after curative treatment. So our hypothesis is that RFA combined with FOLFOX4 can reduce high recurrence rate after RFA for recurrent HCC after hepatectomy. The aim of this open-lable, single prospective study is to evaluate the efficacy and safety of RFA combined with FOLFOX4 systemic chemotherapy for recurrent HCC after partial hepatectomy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RFA+FOLFOX4 | Experimental | Procedure: RFA, Drug: Oxaliplatin, Drug: 5-Fluorouracil/LeucovorinRFA: RFA was performed by using a commercially available system (RF 2000; Radio-Therapeutics Mountain View, CA), and a needle electrode with a 15 Ga insulated cannula with 10 hook-shaped expandable electrode tines with a diameter of 3.5 cm at expansion (LeVeen; RadioTherapeutics). Oxaliplatin + 5-Fluorouracil/Leucovorin: 4 weeks after RFA; Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin Day 1: Oxaliplatin 85mg/m² 2h IV infusion, leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m2 22h IV infusion. Day 2: Leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m² 22h IV infusion. Repeated every 2 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- age 18 - 75 years;
- recurrence of HCC 12 months after initial hepatectomy;
- no other treatment received except for the initial hepatectomy;
- Single tumor≤5cm in diameter; or 2-3 lesions each ≤ 3.0 cm
- lesions visible on ultrasound and with an acceptable and safe path between the lesion and the skin as shown on ultrasound;
Key exclusion criteria (12 listed)
- severe coagulation disorders (prothrombin activity <40% or a platelet count of <40,000 / mm3);
- Child-Pugh class C liver cirrhosis or evidence of hepatic decompensation including ascites, esophageal or gastric variceal bleeding, or hepatic encephalopathy;
- Documented allergy to platinum compound or to other study drugs; Any previous oxaliplatin or doxorubicin treatment, except adjuvant treatment more than 12 months before the randomization.
- Previous or concurrent cancer that is distinct in primary site or histology from HCC
- History of cardiac disease congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is permitted); cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers, calcium channel blocker or digoxin; uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of 3 antihypertensive drugs).
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 |
|---|---|---|
| RFARFA: RFA was performed by using a commercially available system (RF 2000; Radio-Therapeutics Mountain View, CA), and a needle electrode with a 15 Ga insulated cannula with 10 hook-shaped expandable electrode tines with a diameter of 3.5 cm at expansion (LeVeen; RadioTherapeutics). | Procedure or surgery | RFA+FOLFOX4 |
| Oxaliplatin4 weeks after RFA; Drug: Oxaliplatin Day 1: Oxaliplatin 85mg/m² 2h IV infusion. Repeated every 2 weeks | Drug | RFA+FOLFOX4 |
| 5-Fluorouracil/Leucovorin4 weeks after RFA; Drug: 5-Fluorouracil/Leucovorin Day 1, after Oxaliplatin 85mg/m² 2h IV infusion: Leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m2 22h IV infusion. Day 2: Leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m² 22h IV infusion. Repeated every 2 weeks | Drug | RFA+FOLFOX4 |
Primary outcome
Recurrence rate
Time frame: 2 years
Safety and Tolerability
Time frame: 2 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
2 secondary outcomes
Recurrence-free survival
Time frame: 2 years
Overall survival
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2015.
- Background: PubMed 23980077Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. doi: 10.1200/JCO.2012.44.5643. Epub 2013 Aug 26.
- Background: PubMed 23269991Peng ZW, Zhang YJ, Chen MS, Xu L, Liang HH, Lin XJ, Guo RP, Zhang YQ, Lau WY. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol. 2013 Feb 1;31(4):426-32. doi: 10.1200/JCO.2012.42.9936. Epub 2012 Dec 26.
- Background: PubMed 22157201Peng ZW, Zhang YJ, Liang HH, Lin XJ, Guo RP, Chen MS. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology. 2012 Feb;262(2):689-700. doi: 10.1148/radiol.11110637. Epub 2011 Dec 12.
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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.
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 RFA, Oxaliplatin and 5-Fluorouracil/Leucovorin in people with Hepatocellular Carcinoma, 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 7 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 Apr 2015. 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?
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?
Recurrence rate (time frame: 2 years). The study lists 2 primary outcomes in all. 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 NCT02426450, which also lists 3 linked publications.
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 Apr 2015.