Feasibility of High Dose PROton Therapy On Unresectable Primary Carcinoma Of Liver: Prospective Phase II Trial

Liver Neoplasm Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02632864
• Other study ID #: 2015-08-004
• Status: Recruiting
• Phase: Phase 2
• First received: December 7, 2015
• Last updated: April 11, 2018
• Start date: December 2015
• Est. completion date: November 2022

Study information

• Verified date: April 2018
• Source: Samsung Medical Center
• Contact: Joon Hyeok Lee, MD, PhD
• Phone: 82-2-3410-3409
• Email: gijhlee.lee[@]samsung.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The standard treatment of unresectable hepatocellular carcinoma (HCC) is transarterial chemoembolization (TACE) or sorafenib. Though the TACE and the agent showed survival benefit in several randomized phase III trials, the benefit was modest.

Recently, radiotherapy (RT), especially conformal and higher dose with the advancement of RT techniques, showed favorable response rate with acceptable local control rate. Based on those promising results, RT was actively applied in HCC who are not indicated with surgery and/or radiofrequency ablation.

Many researchers reported that there is a relationship between RT dose and tumor response rate. RT dose, however, is frequently limited because the complications (like radiation induced liver disease (RILD), radiation induced gastro-duodenal toxicity, etc.) are also closely related with higher exposed RT dose.

Proton beam has characteristic depth-dose distribution contrast to photon, the "Bragg peak". The advantage of this dose distribution could be more highlighted in HCC management, because of the weakness and maintenance importance of liver function itself in HCC patients. In fact, the superior results of proton beam therapy in HCC were constantly reported in several groups as prospectively as well as retrospectively.

In this background, the investigators planned the present study to evaluate the efficacy and safety of proton beam therapy in HCC patients who are not indicated with surgery and/or radiofrequency ablation (RFA).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: November 2022
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Hepatocellular carcinoma (HCC) patients (Pathologically proven or HCC diagnosed based on American Association for the Study of Liver Diseases (AASLD) guideline)

• Not indicated with surgical resection and/or RFA

• Discussion in tumor board including gastroenterologist, radiologist, radiation oncologist

• Eastern Cooperative Oncology Group performance status 0 to 2 within 1 week before participate

• Adequate bone marrow function (absolute neutrophil count = 1.0 x 109/l, platelet = 30 x 109/l, hemoglobin = 8 g/dl)

• Adequate liver/renal function within 1 week before participate

• Total bilirubin <3.0 mg/dL, Prothrombin time/International normalized ratio <1.7, Albumin=2.8g/dL, Aspartate aminotransferase/alanine aminotransferase<6 times of upper normal limit Serum creatinine < 1.5 x upper normal limit, glomerular filtration rate > 50 ml/min

• Informed consent

• If viable tumor is single, 1 cm to 10 cm

• Less than 3 nodules

• Child-Pugh class A, B, or early C (score = 10)

• Women of childbearing potential and male participants must agree to practice adequate contraception while on study and for at least 6 months following the last dose of RT

Exclusion Criteria:

• Uncontrolled hepatic encephalopathy

• Previous history of upper abdominal radiotherapy

• Status of pregnancy or breast feeding

• Less than 12 weeks of expected survival

• Uncontrolled ascites

• Combined with disease known as radiosensitive disorder (connective tissue disorder, Ataxia-telangiectasia)

• Hard to maintain stable respiration less than 5 minutes related with respiratory disease

• Combined with uncontrolled severe acute disease other than liver

Related Conditions & MeSH terms

• Liver Neoplasm
• Liver Neoplasms
• Proton Therapy

Intervention

Radiation:
• Proton arm
Proton beam therapy

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	two-year overall survival		two-year after proton beam therapy
Secondary	1 month objective response rate	Modified Response Evaluation Criteria In Solid Tumors (mRECIST) will be used.	1 month after proton beam therapy
Secondary	3 month objective response rate	Modified Response Evaluation Criteria In Solid Tumors (mRECIST) will be used.	3 months after proton beam therapy
Secondary	6 month objective response rate	Modified Response Evaluation Criteria In Solid Tumors (mRECIST) will be used.	6 months after proton beam therapy
Secondary	1 year progression free survival	Modified Response Evaluation Criteria In Solid Tumors (mRECIST) will be used.	one-year after proton beam therapy
Secondary	1 year local progression free survival	Modified Response Evaluation Criteria In Solid Tumors (mRECIST) will be used.	one-year after proton beam therapy
Secondary	6 months adverse event	Common Terminology Criteria for Adverse Event v4.0 (CTCAE v4.0) will be used.	6 months after proton beam therapy
Secondary	1 year adverse event	Common Terminology Criteria for Adverse Event v4.0 (CTCAE v4.0) will be used.	1 year after proton beam therapy
Secondary	Baseline Quality of life assessment by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ C-30)		Within 2 week before proton beam therapy started
Secondary	1 month Quality of life assessment by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ C-30) compared with baseline		1 month after proton beam therapy
Secondary	3 month Quality of life assessment by EORTC QLQ C-30 compared with baseline		3 month after proton beam therapy
Secondary	6 month Quality of life assessment by EORTC QLQ C-30 compared with baseline		6 month after proton beam therapy
Secondary	Baseline Indocyanine green (ICG)	ICG Retention rate at 15 minute will be used.	Within 2 week before proton beam therapy started
Secondary	Indocyanine green (ICG) test change compared with baseline	ICG Retention rate at 15 minute will be used.	3 month after proton beam therapy
Secondary	Baseline hepatobiliary phase signal	Hepatobiliary phase (20 minute after gadoxetate disodium injection) will be used to evaluate functioning liver volume.	Within 2 week before proton beam therapy started
Secondary	Hepatobiliary phase signal change after proton beam therapy	Hepatobiliary phase (20 minute after gadoxetate disodium injection) will be used to evaluate functioning liver volume.	3 month after proton beam therapy