Clinical trial NCT02632864: Feasibility of High Dose PROton Therapy On Unresectable Primary Carcinoma Of Liver: Prospective Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Liver Neoplasm
Proton Therapy
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2015-12-17
Enrollment: 66
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: two-year overall survival
timeFrame: two-year after proton beam therapy
Secondary outcomes:
measure: 1 month objective response rate
timeFrame: 1 month after proton beam therapy
measure: 3 month objective response rate
timeFrame: 3 months after proton beam therapy
measure: 6 month objective response rate
timeFrame: 6 months after proton beam therapy
measure: 1 year progression free survival
timeFrame: one-year after proton beam therapy
measure: 1 year local progression free survival
timeFrame: one-year after proton beam therapy
measure: 6 months adverse event
timeFrame: 6 months after proton beam therapy
measure: 1 year adverse event
timeFrame: 1 year after proton beam therapy
measure: Baseline Quality of life assessment by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ C-30)
timeFrame: Within 2 week before proton beam therapy started
measure: 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
timeFrame: 1 month after proton beam therapy
measure: 3 month Quality of life assessment by EORTC QLQ C-30 compared with baseline
timeFrame: 3 month after proton beam therapy
measure: 6 month Quality of life assessment by EORTC QLQ C-30 compared with baseline
timeFrame: 6 month after proton beam therapy
measure: Baseline Indocyanine green (ICG)
timeFrame: Within 2 week before proton beam therapy started
measure: Indocyanine green (ICG) test change compared with baseline
timeFrame: 3 month after proton beam therapy
measure: Baseline hepatobiliary phase signal
timeFrame: Within 2 week before proton beam therapy started
measure: Hepatobiliary phase signal change after proton beam therapy
timeFrame: 3 month after proton beam therapy
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Joon Hyeok Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: