Phase II Trial of Carbon-ion Radiotherapy Combined With GM-CSF for the Treatment of Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
The aim of this research project is to assess the efficacy and toxicity of hypofractionated carbon-ion radiotherapy with concurrent granulocyte-macrophage colony-stimulating factor for the treatment of hepatocellular carcinoma

Detailed Description
-----------------
Golden E.B. et al.in 2015 reported that localized radiotherapy granulocyte-macrophage colony-stimulating factor (GM-CSF) produced objective abscopal responses in solid tumor with metastasises. We hypothesize that hypofractionated carbon-ion radiotherapy combining granulocyte-macrophage colony-stimulating factor (GM-CSF) might improve the clinical response rate and progression-free survival (PFS) in hepatocellular carcinoma. The primary endpoint of the current phase II trial is progression-free survival rate at 2 years, secondary endpoints are overall survival, safety and toxicity.

Official Title
-----------------
A Prospective Phase II Single-institution Trial of Carbon-ion Radiotherapy Combined With Granulocyte-macrophage Colony-stimulating Factor for the Treatment of Hepatocellular Carcinoma

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Radiation: carbon-ion radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: histologically confirmed hepatocellular carcinoma (HCC) or clinical diagnosis of HCC according to American association for the study of liver diseases （AASLD）-guidelines or clinical diagnosis criteria based on Alpha Fetoprotein （AFP), and radiological images proposed by Liver Cancer Society, Chinese Anti-Cancer Association; no clinically distant metastasis; the tumor is away from gastro-intestinal (GI) tract (>1cm); Child Push score A,technically unresectable, or medically inoperable; maximal tumor size is less than 10 cm; age ≥ 18 and <80 years of age; Karnofsky Performance Score ≥ 70; No previous invasive cancer (within 5 years before the HCC diagnosis)except for skin non-melanoma cancer or non muscle invasive bladder cancer; Ability to understand character and individual consequences of the clinical trial; Willing to sign the written informed consent; Informed consent must be signed before the enrollment in the trial; Exclusion Criteria: Distant metastasis (M1); maximal tumor size is more than 10 cm; tumor invading adjacent gastrointestine (T4); Child push score B or C; Previous hepatic radiotherapy; Severe systemic disorders; Previous malignancy (within 5 years) except for skin non-melanoma cancer or 3-year disease free interval from previous malignancy like in situ cervix cancer or non muscle invasive bladder cancer; Non conformity of the radiotherapy dose distribution when compared to the dose constraints; Psychiatric disorders or any other condition that can make unreliable the informed consent;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carbon-ion radiotherapy with GM-CSF<br>Hypofractionated carbon-ion radiotherapy was prescribed at a dose of 40Gray(Gy) [relative biological effectiveness (RBE)] in 5 fractions for intrahepatic cases away from gastro-intestinal (GI) tract (>1cm) with concurrent GM-CSF 125ug/m2/d, subcutaneous injection d1-28; | Radiation: carbon-ion radiotherapy<br>* Hypofractionated carbon-ion radiotherapy was prescribed at a dose of 40Gy RBE in 5 fractions<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival of all patients | Time in months measured from treatment initiation until the date of progression or the date of last follow-up. | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time in months measured from treatment initiation until the date of death or the date of last follow-up. | 2 year | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | Time interval from the start of carbon-ion radiotherapy to 3 months after the completion of carbon-ion radiotherapy] | 
| Objective responses rate |  | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatocellular Carcinoma, carbon-ion radiotherapy, GM-CSF, immunotherapy