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

Phase 2

• Conditions: Liver Neoplasm; Proton Therapy
• Interventions: Radiation: Proton arm

• Registration Number: NCT02632864
• Lead Sponsor: Samsung Medical Center

Brief 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).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2015-12
• Study First Submitted: 2015-12-07
• Study First Submitted QC: 2015-12-14
• Study First Posted: 2015-12-17
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-11
• Last Update Posted: 2018-04-12
• Primary Completion: 2019-10
• Study Completion: 2022-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 66

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Proton arm	Proton arm	Proton beam therapy

Primary Outcome Measures

Name	Time	Method
two-year overall survival	two-year after proton beam therapy

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of