Hepatocellular CarcinomaNCT03322280
TACE Combined With Iodine-125 Seeds Implantation for HCC
A study testing TACE combined with iodine-125 seeds implantation and TACE in people with Hepatocellular Carcinoma and Portal Vein Occlusion, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
Portal vein tumour thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC). PVTT has a profound adverse effect on prognosis, with a very short median survival time (2-4 months). The presence of PVTT also limits treatment options, such as liver transplantation and curative resection. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma, Portal Vein Occlusion, Tumor Thrombus
- What is being tested?
- TACE combined with iodine-125 seeds implantation and TACE
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2018to 30 Jun 2022
- Phase
- Interventional
- 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
- clinical diagnosis of HCC;
- age between18 and 75 years;
- type I PVTT, type II PVTT, or type III PVTT within 1.5cm extending in the main portal vein (if obstructive PVTT involve both the left and right portal vein or main portal vein, multiple collateral vessels are required);
- Child-Pugh class A or B;
- Eastern Cooperative Group performance status (ECOG) score of 0-2;
- neutrophilic granulocyte count ≥ 1.5×10^9/L, platelet count ≥ 30×10^9/L, and hemoglobin level ≥ 85g/L;
- serum bilirubin ≤ 51.3 μmol/L, albumin ≥ 28g/L, ALT and AST ≤ 5 times of the upper normal limit, and creatinine ≤ 20g/L;
- prothrombin time ≤18s or international normalized ratio < 1.7.
Who cannot join
- diffuse HCC;
- extrahepatic metastasis;
- obstructive PVTT involving both the left and right portal vein or main portal vein without collateral vessels,
- type III PVTT affecting the main portal vein more than 1.5cm, or type IV PVTT;
- previously surgery (resection or liver transplantation), local-regional therapies (e.g., radiofrequency ablation), intra-arterial chemoinfusion, TACE, radiotherapy, systemic chemotherapy, or molecular targeted drug therapy for HCC;
- serious medical comorbidities.
Trial locations and contacts
1 site in 1 country.
China1 site
The 2nd Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510260
About this study
Official title: TACE Combined With Iodine-125 Seeds Implantation Versus TACE Alone for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Prospective, Multicenter, Randomized, Controlled Study
Portal vein tumour thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC). PVTT has a profound adverse effect on prognosis, with a very short median survival time (2-4 months). The presence of PVTT also limits treatment options, such as liver transplantation and curative resection. Although the Barcelona Clinic Liver Cancer group recommended sorafenib as a standard therapy for advanced-stage HCC, the optimal treatment for HCC with PVTT remains largely controversial.
Some studies have reported a survival benefit in patients with PVTT who underwent transarterial chemoembolization (TACE), even in patients with main portal vein (MPV) tumor thrombus. Iodine-125 brachytherapy had also showed promising efficacy as a new method for unresectable HCC with PVTT. Results of our previous study indicated that TACE combined with Iodine-125 seeds implantation might be a good choice for selected patients with PVTT. Thus, we conduct this study to farther evaluate the effect of TACE combined with Iodine-125 seeds implantation for HCC with PVTT.
Read more
270 patients with HCC and PVTT will be included and randomized to two group: group 1, patients received TACE combined with Iodine-125 seeds implantation; group 2, patients received TACE alone. TACE and Iodine-125 seeds implantation will be performed with a standardized procedure. Iodine-125 seeds implantation into PVTT (guided by CT) will be conducted 7 days after TACE.
All patients revisit our institutions for follow-up examinations including contrast enhanced CT/MRI and laboratory tests every 4-6 weeks after the first treatment. Patients who have a tumor response rating of complete response will be required to revisit 3 months interval. At each visit, TACE or Iodine-125 seeds implantation is repeated if the following criteria are reached: 1) images indicating viable intrahepatic tumor tissue or PVTT; 2) Child-Pugh class A or B, and no contraindication to TACE and Iodine-125 seeds implantation.
The primary end point of this study is overall survival. The secondary end points are time to tumor progression, disease control rate, duration of portal patency and adverse events. All adverse events are graded in accordance with Common Toxicity Criteria Adverse Events Version (CTCAE) 4.03.
Read the detailed description
Background and purpose:
Hepatocellular carcinoma (HCC) is the 5th most common cancer in the world and the 3rd most prevalent cause of tumor-related deaths. Portal vein tumor thrombus (PVTT) occurs in up to 44% of HCC patients at the time of death and approximately 10-40% of patients at time of diagnosis. PVTT has a profound adverse effect on prognosis, with a very short median survival time (2-4 months). The presence of PVTT also limits treatment options, such as liver transplantation and curative resection. The optimal treatment for patients with HCC and PVTT remains largely controversial.
The Barcelona Clinic Liver Cancer (BCLC) group recommended the tyrosine kinase inhibitor sorafenib as a standard therapy for patients with advanced-stage HCC (BCLC stage C), including HCC patients with PVTT. However, in the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trail, on which the BCLC recommendations were based, patients with vascular invasion represented only 38.4% of the total study population. This result may not directly imply a survival gain with sorafenib treatment in HCC patients with PVTT. Additionally, the median survival time for patients with advanced HCC, including vascular invasion or extrahepatic metastases, treated with sorafenib is short - only 6.5 months in Asia. Thus, more effective treatment strategies have been strongly required to increase survival rate.
Some studies have reported a survival benefit in patients with PVTT who underwent transarterial chemoembolization (TACE), even in patients with main portal vein tumor thrombus. Iodine-125 brachytherapy alone had also showed promising efficacy as a new method for unresectable HCC with PVTT. Results of our previous study indicated that TACE combined with Iodine-125 seeds implantation might be a good choice for selected patients with PVTT. Thus, we conduct this study to farther evaluate the effect of TACE combined with Iodine-125 seeds implantation for HCC with PVTT.
Methods:
HCC was diagnosed by biopsy or according to the non-invasive criteria following the European Association for the Study of Liver/American Association for the study of Liver Disease guidelines. The presence of PVTT was confirmed by three-phase dynamic CT or MR. The types of PVTT were classified into four subgroups: type I, PVTT in segmental branches of portal vein or above; type II, PVTT affecting left/right portal vein; type III, PVTT affecting main portal vein (MPV); and type IV, PVTT affecting superior mesenteric vein (SMV).
270 patients met the eligibility criteria will be included in this study and randomized to two group: group 1, patients received TACE combined with Iodine-125 seeds implantation; group 2, patients received TACE alone.
TACE procedure:
solution of doxorubicin hydrochloride (20-40 mg) and 5-Fu (500-1000 mg) is infused into the feeder vessels of HCC. Then, An emulsion of 2-20 ml lipiodol and 20-50 mg lobaplatin is administered into the feeder vessels. The total amount of chemotherapy drugs is depended on the patient's body weight. Finally, gelatin sponge or polyvinyl alcohol (PVA) particles, which are mixed with contrast material, were administered into the feeder vessels until stasis of arterial flow was achieved. In patients with an arterioportal shunt, embolization with 300-1000 μm PVA is performed to occlude the shunt by superselective catheterization before infusion of lipiodol and lobaplatin emulsion.
Iodine-125 seeds implantation procedure:
Iodine-125 seeds implantation into PVTT is conducted 7 days after TACE when liver function tests demonstrated values comparable to those obtained before TACE. Each particle was 4.5 mm in length and 0.8 mm in diameter, with a radioactivity of 0.6-0.8mCi, radioactive half-life of 60.1days, and radiation energy of 27.4KeV. The volume and shape of PVTT is obtained by CT/MR images and used to calculate the matched peripheral dose and determine best percutaneous access route and numbers of Iodine-125 seeds using our three dimensional conformal radiation therapy Treatment Planning System (TPS). Implantation was guided by CT and Iodine-125 seeds are implanted into inside PVTT or around the PVTT (parenchymal or tumor issue from PVTT less than 1.7 cm) 5 mm apart along the length of PVTT using 18G needles.
Follow-up and re-treatment:
All patients revisit our institution for follow-up examinations including contrast enhanced CT/MRI every 4-6 weeks after the first treatment. The laboratory tests are checked within one week before and after the first TACE or Iodine-125 seed implantation, and every 4-6 weeks during follow-up. Patients who have a tumor response rating of complete response will be required to revisit 3 months interval. At each visit, TACE or Iodine-125 seed implantation or combination of TACE and Iodine-125 seed is repeated if the following criteria are reached: 1) images indicating viable intrahepatic tumor tissue or PVTT; 2) Child-Pugh class A or B, and no contraindication to TACE and Iodine-125 seeds implantation.
- Being tested
- TACE combined with iodine-125 seeds implantation, TACE
- Keywords
- Hepatocellular carcinoma, Portal vein tumor thrombus, Transcatheter arterial chemoembolization, iodine-125 seed
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TACE combined with iodine-125 seeds implantationProcedure or surgery
Conventional TACE with lipiodol was performed. Then Iodine-125 seed implantation into PVTT is conducted 7-10 days after TACE when liver function tests demonstrated values comparable to those obtained before TACE.
TACEProcedure or surgery
Only conventional TACE with lipiodol and chemotherapy drugs was performed.
| Study group | Role | What they receive |
|---|---|---|
| TACE+I-125 seeds | Experimental | TACE combined with iodine-125 seeds implantation Receives: Procedure: TACE combined with iodine-125 seeds implantation |
| TACE alone | Active comparator | TACE alone Receives: Procedure: TACE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
The time from date of randomization to death due to any cause.
Measured: 24 months
Secondary outcomes (6)
Adverse events
Side effects of TACE and iodine-125 seeds implantation were reported according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Measured: 24 months
Progression free survival (PFS)
The time from randomization until the first occurrence of PD or death due to any cause, whichever occurs first.
Measured: 24 months
Time to tumor progression (TTP)
The time from randomization until the date that disease progression (PD) was confirmed radiologically.
Measured: 24 months
Objective response rate (ORR)
The percentage of patients who had a best overall tumor response rating of CR or PR.
Measured: 24 months
Disease control rate (DCR)
Tumor response was evaluated with contrast-enhanced CT or MR imaging according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Disease control rate was defined as the percentage of patients who had a best tumor response rating of complete response (CR), partial response (PR), or stable disease (SD), which was maintained for at least 4 weeks from the first manifestation of that modified Response Evaluation Criteria Solid Tumors rating.
Measured: 24 months
Duration of portal patency
The time from randomization until the date that complete portal vein occlusion was confirmed (if the portal vein is patent at diagnosis).
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2017
- Study start1 Jul 2018
- Primary completion18 Sep 2021
- Study completion30 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)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 Second Affiliated Hospital of Guangzhou Medical 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- ZhuHai Hospital, First People's Hospital of Zhaoqing, Foshan Sanshui District People's Hospital, Fifth Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial People's Hospital, Sun Yat-sen University, Third Affiliated Hospital, Sun Yat-Sen University
- Responsible party
- Sponsor
- Investigators
- Kangshun Zhu, MD, Study chair, Second Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03322280
- Sponsor's protocol ID
- MIIR-01
- Status last verified
- Mar 2022
- First submitted
- 9 Jun 2017
- Last updated
- 3 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007 Jun;132(7):2557-76. doi: 10.1053/j.gastro.2007.04.061.
PubMed 17570226Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30. doi: 10.3322/canjclin.55.1.10.
PubMed 15661684Pirisi M, Avellini C, Fabris C, Scott C, Bardus P, Soardo G, Beltrami CA, Bartoli E. Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study. J Cancer Res Clin Oncol. 1998;124(7):397-400. doi: 10.1007/s004320050189.
PubMed 9719503Cheung TK, Lai CL, Wong BC, Fung J, Yuen MF. Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong. Aliment Pharmacol Ther. 2006 Aug 15;24(4):573-83. doi: 10.1111/j.1365-2036.2006.03029.x.
PubMed 16907890Minagawa M, Makuuchi M. Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. World J Gastroenterol. 2006 Dec 21;12(47):7561-7. doi: 10.3748/wjg.v12.i47.7561.
PubMed 17171782Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, Bru C, Rodes J, Bruix J. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999 Jan;29(1):62-7. doi: 10.1002/hep.510290145.
PubMed 9862851Schoniger-Hekele M, Muller C, Kutilek M, Oesterreicher C, Ferenci P, Gangl A. Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut. 2001 Jan;48(1):103-9. doi: 10.1136/gut.48.1.103.
PubMed 11115830Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, Kudo M, Lee JM, Choi BI, Poon RT, Shiina S, Cheng AL, Jia JD, Obi S, Han KH, Jafri W, Chow P, Lim SG, Chawla YK, Budihusodo U, Gani RA, Lesmana CR, Putranto TA, Liaw YF, Sarin SK. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010 Mar 18;4(2):439-74. doi: 10.1007/s12072-010-9165-7.
PubMed 20827404Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010 Feb;30(1):61-74. doi: 10.1055/s-0030-1247133. Epub 2010 Feb 19.
PubMed 20175034Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.
PubMed 19095497Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.
PubMed 18650514Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329-38. doi: 10.1055/s-2007-1007122.
PubMed 10518312Pinter M, Hucke F, Graziadei I, Vogel W, Maieron A, Konigsberg R, Stauber R, Grunberger B, Muller C, Kolblinger C, Peck-Radosavljevic M, Sieghart W. Advanced-stage hepatocellular carcinoma: transarterial chemoembolization versus sorafenib. Radiology. 2012 May;263(2):590-9. doi: 10.1148/radiol.12111550. Epub 2012 Mar 21.
PubMed 22438359Chung GE, Lee JH, Kim HY, Hwang SY, Kim JS, Chung JW, Yoon JH, Lee HS, Kim YJ. Transarterial chemoembolization can be safely performed in patients with hepatocellular carcinoma invading the main portal vein and may improve the overall survival. Radiology. 2011 Feb;258(2):627-34. doi: 10.1148/radiol.10101058.
PubMed 21273524Lee HS, Kim JS, Choi IJ, Chung JW, Park JH, Kim CY. The safety and efficacy of transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma and main portal vein obstruction. A prospective controlled study. Cancer. 1997 Jun 1;79(11):2087-94.
PubMed 9179054
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TACE Combined With Iodine-125 Seeds Implantation Versus TACE Alone for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Prospective, Multicenter, Randomized, Controlled Study
- ClinicalTrials.gov ID
- NCT03322280
- Acronym / sponsor ID
- MIIR-01
- Keywords
- Hepatocellular carcinoma, Portal vein tumor thrombus, Transcatheter arterial chemoembolization, iodine-125 seed
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Collaborators
- ZhuHai Hospital, First People's Hospital of Zhaoqing, Foshan Sanshui District People's Hospital, Fifth Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial People's Hospital, Sun Yat-sen University, Third Affiliated Hospital, Sun Yat-Sen University
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 18 Sep 2021 (actual)
- Study completion
- 30 Jun 2022 (estimated)
- First posted
- 26 Oct 2017 (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.
Portal vein tumour thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC). PVTT has a profound adverse effect on prognosis, with a very short median survival time (2-4 months). The presence of PVTT also limits treatment options, such as liver transplantation and curative resection. Although the Barcelona Clinic Liver Cancer group recommended sorafenib as a standard therapy for advanced-stage HCC, the optimal treatment for HCC with PVTT remains largely controversial.
Some studies have reported a survival benefit in patients with PVTT who underwent transarterial chemoembolization (TACE), even in patients with main portal vein (MPV) tumor thrombus. Iodine-125 brachytherapy had also showed promising efficacy as a new method for unresectable HCC with PVTT. Results of our previous study indicated that TACE combined with Iodine-125 seeds implantation might be a good choice for selected patients with PVTT. Thus, we conduct this study to farther evaluate the effect of TACE combined with Iodine-125 seeds implantation for HCC with PVTT.
270 patients with HCC and PVTT will be included and randomized to two group: group 1, patients received TACE combined with Iodine-125 seeds implantation; group 2, patients received TACE alone. TACE and Iodine-125 seeds implantation will be performed with a standardized procedure. Iodine-125 seeds implantation into PVTT (guided by CT) will be conducted 7 days after TACE.
All patients revisit our institutions for follow-up examinations including contrast enhanced CT/MRI and laboratory tests every 4-6 weeks after the first treatment. Patients who have a tumor response rating of complete response will be required to revisit 3 months interval. At each visit, TACE or Iodine-125 seeds implantation is repeated if the following criteria are reached: 1) images indicating viable intrahepatic tumor tissue or PVTT; 2) Child-Pugh class A or B, and no contraindication to TACE and Iodine-125 seeds implantation.
The primary end point of this study is overall survival. The secondary end points are time to tumor progression, disease control rate, duration of portal patency and adverse events. All adverse events are graded in accordance with Common Toxicity Criteria Adverse Events Version (CTCAE) 4.03.
Detailed description
Background and purpose:
Hepatocellular carcinoma (HCC) is the 5th most common cancer in the world and the 3rd most prevalent cause of tumor-related deaths. Portal vein tumor thrombus (PVTT) occurs in up to 44% of HCC patients at the time of death and approximately 10-40% of patients at time of diagnosis. PVTT has a profound adverse effect on prognosis, with a very short median survival time (2-4 months). The presence of PVTT also limits treatment options, such as liver transplantation and curative resection. The optimal treatment for patients with HCC and PVTT remains largely controversial.
The Barcelona Clinic Liver Cancer (BCLC) group recommended the tyrosine kinase inhibitor sorafenib as a standard therapy for patients with advanced-stage HCC (BCLC stage C), including HCC patients with PVTT. However, in the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trail, on which the BCLC recommendations were based, patients with vascular invasion represented only 38.4% of the total study population. This result may not directly imply a survival gain with sorafenib treatment in HCC patients with PVTT. Additionally, the median survival time for patients with advanced HCC, including vascular invasion or extrahepatic metastases, treated with sorafenib is short - only 6.5 months in Asia. Thus, more effective treatment strategies have been strongly required to increase survival rate.
Some studies have reported a survival benefit in patients with PVTT who underwent transarterial chemoembolization (TACE), even in patients with main portal vein tumor thrombus. Iodine-125 brachytherapy alone had also showed promising efficacy as a new method for unresectable HCC with PVTT. Results of our previous study indicated that TACE combined with Iodine-125 seeds implantation might be a good choice for selected patients with PVTT. Thus, we conduct this study to farther evaluate the effect of TACE combined with Iodine-125 seeds implantation for HCC with PVTT.
Methods:
HCC was diagnosed by biopsy or according to the non-invasive criteria following the European Association for the Study of Liver/American Association for the study of Liver Disease guidelines. The presence of PVTT was confirmed by three-phase dynamic CT or MR. The types of PVTT were classified into four subgroups: type I, PVTT in segmental branches of portal vein or above; type II, PVTT affecting left/right portal vein; type III, PVTT affecting main portal vein (MPV); and type IV, PVTT affecting superior mesenteric vein (SMV).
270 patients met the eligibility criteria will be included in this study and randomized to two group: group 1, patients received TACE combined with Iodine-125 seeds implantation; group 2, patients received TACE alone.
TACE procedure:
solution of doxorubicin hydrochloride (20-40 mg) and 5-Fu (500-1000 mg) is infused into the feeder vessels of HCC. Then, An emulsion of 2-20 ml lipiodol and 20-50 mg lobaplatin is administered into the feeder vessels. The total amount of chemotherapy drugs is depended on the patient's body weight. Finally, gelatin sponge or polyvinyl alcohol (PVA) particles, which are mixed with contrast material, were administered into the feeder vessels until stasis of arterial flow was achieved. In patients with an arterioportal shunt, embolization with 300-1000 μm PVA is performed to occlude the shunt by superselective catheterization before infusion of lipiodol and lobaplatin emulsion.
Iodine-125 seeds implantation procedure:
Iodine-125 seeds implantation into PVTT is conducted 7 days after TACE when liver function tests demonstrated values comparable to those obtained before TACE. Each particle was 4.5 mm in length and 0.8 mm in diameter, with a radioactivity of 0.6-0.8mCi, radioactive half-life of 60.1days, and radiation energy of 27.4KeV. The volume and shape of PVTT is obtained by CT/MR images and used to calculate the matched peripheral dose and determine best percutaneous access route and numbers of Iodine-125 seeds using our three dimensional conformal radiation therapy Treatment Planning System (TPS). Implantation was guided by CT and Iodine-125 seeds are implanted into inside PVTT or around the PVTT (parenchymal or tumor issue from PVTT less than 1.7 cm) 5 mm apart along the length of PVTT using 18G needles.
Follow-up and re-treatment:
All patients revisit our institution for follow-up examinations including contrast enhanced CT/MRI every 4-6 weeks after the first treatment. The laboratory tests are checked within one week before and after the first TACE or Iodine-125 seed implantation, and every 4-6 weeks during follow-up. Patients who have a tumor response rating of complete response will be required to revisit 3 months interval. At each visit, TACE or Iodine-125 seed implantation or combination of TACE and Iodine-125 seed is repeated if the following criteria are reached: 1) images indicating viable intrahepatic tumor tissue or PVTT; 2) Child-Pugh class A or B, and no contraindication to TACE and Iodine-125 seeds implantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TACE+I-125 seeds | Experimental | Procedure: TACE combined with iodine-125 seeds implantationTACE combined with iodine-125 seeds implantation |
| TACE alone | Active comparator | Procedure: TACETACE alone |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- clinical diagnosis of HCC;
- age between18 and 75 years;
- type I PVTT, type II PVTT, or type III PVTT within 1.5cm extending in the main portal vein (if obstructive PVTT involve both the left and right portal vein or main portal vein, multiple collateral vessels are required);
- Child-Pugh class A or B;
- Eastern Cooperative Group performance status (ECOG) score of 0-2;
Key exclusion criteria (6 listed)
- diffuse HCC;
- extrahepatic metastasis;
- obstructive PVTT involving both the left and right portal vein or main portal vein without collateral vessels,
- type III PVTT affecting the main portal vein more than 1.5cm, or type IV PVTT;
- previously surgery (resection or liver transplantation), local-regional therapies (e.g., radiofrequency ablation), intra-arterial chemoinfusion, TACE, radiotherapy, systemic chemotherapy, or molecular targeted drug therapy for HCC;
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 |
|---|---|---|
| TACE combined with iodine-125 seeds implantationConventional TACE with lipiodol was performed. Then Iodine-125 seed implantation into PVTT is conducted 7-10 days after TACE when liver function tests demonstrated values comparable to those obtained before TACE. | Procedure or surgery | TACE+I-125 seeds |
| TACEOnly conventional TACE with lipiodol and chemotherapy drugs was performed. | Procedure or surgery | TACE alone |
Primary outcome
Overall survival (OS)
Time frame: 24 months
The time from date of randomization to death due to any cause.
6 secondary outcomes
Adverse events
Time frame: 24 months
Progression free survival (PFS)
Time frame: 24 months
Time to tumor progression (TTP)
Time frame: 24 months
Objective response rate (ORR)
Time frame: 24 months
Disease control rate (DCR)
Time frame: 24 months
Duration of portal patency
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2022.
- Background: PubMed 17570226El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007 Jun;132(7):2557-76. doi: 10.1053/j.gastro.2007.04.061.
- Background: PubMed 15661684Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30. doi: 10.3322/canjclin.55.1.10.
- Background: PubMed 9719503Pirisi M, Avellini C, Fabris C, Scott C, Bardus P, Soardo G, Beltrami CA, Bartoli E. Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study. J Cancer Res Clin Oncol. 1998;124(7):397-400. doi: 10.1007/s004320050189.
- Background: PubMed 16907890Cheung TK, Lai CL, Wong BC, Fung J, Yuen MF. Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong. Aliment Pharmacol Ther. 2006 Aug 15;24(4):573-83. doi: 10.1111/j.1365-2036.2006.03029.x.
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- Individual participant dataSharing planned: Undecided
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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.
Kangshun Zhu, MD study chair
Second Affiliated Hospital of Guangzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TACE combined with iodine-125 seeds implantation and TACE in people with Hepatocellular Carcinoma and Portal Vein Occlusion, run by Second Affiliated Hospital of Guangzhou Medical 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 8 inclusion and 6 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 3 Mar 2022. 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.
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?
Overall survival (OS) (time frame: 24 months). 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 NCT03322280, which also lists 20 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 3 Mar 2022.