Hepatocellular CarcinomaPhase 2NCT02425605
Efficacy of Localized Concurrent Chemo-radiation Therapy and Sorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma
A Phase 2 study testing CCRT and sorafenib in people with Hepatocellular Carcinoma, run by Yonsei University at 1 site in South Korea.
Trial summary
This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential therapy in subjects with advanced HCC. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- CCRT and sorafenib
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteSouth Korea
- Study dates
- 3 Dec 2014to 22 Sep 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have confirmed diagnosis of unresectable hepatocellular carcinoma (HCC) categorized to stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system with any of following criteria: 1) Lesion limited to a single lobe that is within the radiotherapy field, 2) Lesion not limited to a single lobe, but the lesion that is not within the radiotherapy field can be controlled by transarterial chemoembolization or radiofrequency ablation, 3) Presence of metastatic lesions that measure < 1.0 cm in the long axis, 4) The lesion can be accurately measured in at least one dimension as ≥ 1.0 cm
- Males or females aged at least 20 years and below 76 years
- Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 or 1
- Adequate liver function, defined as: 1) Child-Pugh score ≤ 7, 2) Bilirubin ≤ 3.0 mg/dL
- Adequate bone marrow function, defined as: 1) Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, 2) White blood cell count (WBC) ≥ 4.0 × 109/L, 3) Platelet count ≥ 60 × 109/L
- Adequate renal function, defined as serum creatinine < 2.0 mg/dL
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- Subjects with hepatitis B virus (HBV)-related HCC must have adequately controlled HBV replication status
- Adequate blood coagulation factors, defined as international normalized ratio (INR) ≤ 2.3
- Provide written informed consent
- Willing and able to comply with all aspects of the protocol
Who cannot join
- Significant liver function impairment, defined as bilirubin > 3.0 mg/dL or uncontrolled ascites
- Imaging findings for HCC corresponding to any of the following: 1) Diffuse HCC with > 50% liver occupation, that is not adequate for external radiotherapy, 2) Presence of metastatic lesions that measure ≥ 1.0 cm in the long axis
- Uncontrolled significant active infection
- Presence of active malignancy (except for HCC)
- Females who are lactating or pregnant; females of childbearing potential who have not received pregnancy test or shown positive on pregnancy test
- Any medical or other condition that in the opinion of the investigator would preclude the subject's participation in a clinical study
- Major surgery within 4 weeks prior to enrollment
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Department of Internal Medicine, Yonsei University College of Medicine
Seoul, 120-752
About this study
Official title: Efficacy of Localized Concurrent Chemo-radiation Therapy and Sorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: a Prospective Phase 2 Trial
This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential therapy in subjects with advanced HCC. Approximately 47 subjects will be enrolled and will receive CCRT and sorafenib sequentially until all-cause mortality.
Read the detailed description
This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential therapy in subjects with advanced HCC. Approximately 47 subjects will be enrolled and will receive CCRT and sorafenib sequentially until all-cause mortality.
Sorafenib is the current standard of care for advanced hepatocellular carcinoma (HCC) patients following clinical results from the two pivotal trials in Western and Asian patients. The median overall survival in patients with unresectable hepatocellular carcinoma (HCC) who are treated with sorafenib have shown to be approximately 14 months. However in the presence of portal vein invasion or extrahepatic metastases, the median overall survival is significantly lowered to 5.6 - 8.9 months.
Going forward, improvement in patient-related outcomes would be highly desirable.
A pilot study has been conducted in subjects with advanced HCC with portal vein invasion for which effective therapeutic methods have not been established. This was a single-center, open-label study of localized concurrent chemoradiation therapy (CCRT) for locally advanced HCC patients with portal vein invasion. A total of 40 subjects with advanced HCC with portal vein invasion were enrolled. The subjects were treated with a total of 45 Gy of external beam radiotherapy (1.8 Gy per session, 5 sessions a week, for 5 weeks), with hepatic arterial infusion of 5-flourouracil (5-FU) during the first and last 5 days of radiation therapy (5-FU 500 mg infusion for 5 hours) through the pre-inserted chemoport. Eighteen (45%) subjects had an objective tumor response at 1 month after completion of localized CCRT. The 3-year survival rate was 24.2% and median overall survival was 13.1 months.
Treatment-related serious adverse events (CTCAE grade 3 or higher) were anemia, leukopenia, thrombocytopenia, mucositis and liver decompensation, and their rates were 2.5%, 2.4-5.0%, 17.5%, 10% and 7.3-17.5%, respectively. In addition, 2.4-5.0% of adverse events were chemoport-related adverse events including infection and port obstruction.
Although sorafenib has been shown to increase overall survival in advanced HCC patients as compared to placebo through anti-angiogenesis effect, its tumoricidal effect is not evident. Meanwhile, based on the above analysis from the pilot study, localized CCRT has been regarded as a promising treatment with tumoricidal effect for advanced HCC patients. Therefore, combining sorafenib treatment with CCRT is anticipated to augment anti-tumor effect and improve tumor response and median overall survival.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- CCRT, sorafenib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CCRTRadiation
Also called Localized concurrent chemoradiation therapy(CCRT)
The subject is treated with a total of 45 Gy of external beam radiotherapy (1.8 Gy per session, 5 sessions a week, for 5 weeks), with hepatic arterial infusion of 5-flourouracil (5-FU) during the first and last 5 days of radiation therapy (5-FU 500 mg infusion for 5 hours) for radiosensitization through the pre-inserted chemoport.
sorafenibDrug
Also called sorafenib(Nexavar®) sequential therapy
Four weeks after completion of CCRT, the subject is given daily sorafenib treatment and will be followed for survival.
| Study group | Role | What they receive |
|---|---|---|
| CCRT-sorafenib group | Experimental | Not described Receives: Radiation: CCRT; Drug: sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measured: 36 months after the enrollment
Secondary outcomes (4)
PFSL defined as dynamic CT scan
Progression-free survival in the liver(PFSL)
Measured: 36 months after the enrollment
PFSO defined as definitive imaging technique
progression-free survival overall (PFSO)
Measured: 36 months after the enrollment
tumor response defined as modified RECIST
Measured: 36 months after the enrollment
toxicity defined as NCI-CTC(version 4.02)
toxicity defined as National Cancer Institute-Common Toxicity Criteria (version 4.02)
Measured: 36 months after the enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2015 (estimated)
- Study start3 Dec 2014
- Primary completion22 Sep 2017
- Study completion22 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Yonsei 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Beom Kyung Kim, M.D., Ph.D., Principal investigator, Severance Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02425605
- Sponsor's protocol ID
- 4-2014-0803
- Status last verified
- Feb 2019
- First submitted
- 14 Apr 2015
- Last updated
- 25 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Localized Concurrent Chemo-radiation Therapy and Sorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: a Prospective Phase 2 Trial
- ClinicalTrials.gov ID
- NCT02425605
- Acronym / sponsor ID
- 4-2014-0803
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 3 Dec 2014
- Primary completion
- 22 Sep 2017 (actual)
- Study completion
- 22 Sep 2017 (actual)
- First posted
- 24 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.
This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential therapy in subjects with advanced HCC. Approximately 47 subjects will be enrolled and will receive CCRT and sorafenib sequentially until all-cause mortality.
Detailed description
This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential therapy in subjects with advanced HCC. Approximately 47 subjects will be enrolled and will receive CCRT and sorafenib sequentially until all-cause mortality.
Sorafenib is the current standard of care for advanced hepatocellular carcinoma (HCC) patients following clinical results from the two pivotal trials in Western and Asian patients. The median overall survival in patients with unresectable hepatocellular carcinoma (HCC) who are treated with sorafenib have shown to be approximately 14 months. However in the presence of portal vein invasion or extrahepatic metastases, the median overall survival is significantly lowered to 5.6 - 8.9 months.
Going forward, improvement in patient-related outcomes would be highly desirable.
A pilot study has been conducted in subjects with advanced HCC with portal vein invasion for which effective therapeutic methods have not been established. This was a single-center, open-label study of localized concurrent chemoradiation therapy (CCRT) for locally advanced HCC patients with portal vein invasion. A total of 40 subjects with advanced HCC with portal vein invasion were enrolled. The subjects were treated with a total of 45 Gy of external beam radiotherapy (1.8 Gy per session, 5 sessions a week, for 5 weeks), with hepatic arterial infusion of 5-flourouracil (5-FU) during the first and last 5 days of radiation therapy (5-FU 500 mg infusion for 5 hours) through the pre-inserted chemoport. Eighteen (45%) subjects had an objective tumor response at 1 month after completion of localized CCRT. The 3-year survival rate was 24.2% and median overall survival was 13.1 months.
Treatment-related serious adverse events (CTCAE grade 3 or higher) were anemia, leukopenia, thrombocytopenia, mucositis and liver decompensation, and their rates were 2.5%, 2.4-5.0%, 17.5%, 10% and 7.3-17.5%, respectively. In addition, 2.4-5.0% of adverse events were chemoport-related adverse events including infection and port obstruction.
Although sorafenib has been shown to increase overall survival in advanced HCC patients as compared to placebo through anti-angiogenesis effect, its tumoricidal effect is not evident. Meanwhile, based on the above analysis from the pilot study, localized CCRT has been regarded as a promising treatment with tumoricidal effect for advanced HCC patients. Therefore, combining sorafenib treatment with CCRT is anticipated to augment anti-tumor effect and improve tumor response and median overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CCRT-sorafenib group | Experimental | Radiation: CCRT, Drug: sorafenib |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects must have confirmed diagnosis of unresectable hepatocellular carcinoma (HCC) categorized to stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system with any of following criteria: 1) Lesion limited to a single lobe that is within the radiotherapy field, 2) Lesion not limited to a single lobe, but the lesion that is not within the radiotherapy field can be controlled by transarterial chemoembolization or radiofrequency ablation, 3) Presence of metastatic lesions that measure < 1.0 cm in the long axis, 4) The lesion can be accurately measured in at least one dimension as ≥ 1.0 cm
- Males or females aged at least 20 years and below 76 years
- Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 or 1
- Adequate liver function, defined as: 1) Child-Pugh score ≤ 7, 2) Bilirubin ≤ 3.0 mg/dL
- Adequate bone marrow function, defined as: 1) Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, 2) White blood cell count (WBC) ≥ 4.0 × 109/L, 3) Platelet count ≥ 60 × 109/L
Key exclusion criteria (7 listed)
- Significant liver function impairment, defined as bilirubin > 3.0 mg/dL or uncontrolled ascites
- Imaging findings for HCC corresponding to any of the following: 1) Diffuse HCC with > 50% liver occupation, that is not adequate for external radiotherapy, 2) Presence of metastatic lesions that measure ≥ 1.0 cm in the long axis
- Uncontrolled significant active infection
- Presence of active malignancy (except for HCC)
- Females who are lactating or pregnant; females of childbearing potential who have not received pregnancy test or shown positive on pregnancy test
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 |
|---|---|---|
| CCRTAlso: Localized concurrent chemoradiation therapy(CCRT)The subject is treated with a total of 45 Gy of external beam radiotherapy (1.8 Gy per session, 5 sessions a week, for 5 weeks), with hepatic arterial infusion of 5-flourouracil (5-FU) during the first and last 5 days of radiation therapy (5-FU 500 mg infusion for 5 hours) for radiosensitization through the pre-inserted chemoport. | Radiation | CCRT-sorafenib group |
| sorafenibAlso: sorafenib(Nexavar®) sequential therapyFour weeks after completion of CCRT, the subject is given daily sorafenib treatment and will be followed for survival. | Drug | CCRT-sorafenib group |
Primary outcome
Overall survival
Time frame: 36 months after the enrollment
4 secondary outcomes
PFSL defined as dynamic CT scan
Time frame: 36 months after the enrollment
PFSO defined as definitive imaging technique
Time frame: 36 months after the enrollment
tumor response defined as modified RECIST
Time frame: 36 months after the enrollment
toxicity defined as NCI-CTC(version 4.02)
Time frame: 36 months after the enrollment
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 25 Feb 2019.
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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.
Beom Kyung Kim, M.D., Ph.D. principal investigator
Severance Hospital
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 CCRT and sorafenib in people with Hepatocellular Carcinoma, run by Yonsei University at 1 site in South Korea.
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 7 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 25 Feb 2019. 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 South Korea. 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?
Overall survival (time frame: 36 months after the enrollment). 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 25 Feb 2019.