Advanced Hepatocellular Carcinoma, Chemotherapy, Stereotactic Body Radiotherapy
Conditions
Keywords
atezolizumab-bevacizumab, SBRT
Brief summary
To determine the efficacy and safety of atezolizumab-bevacizumab combination therapy plus stereotactic body radiotherapy(SBRT) in patients with advanced hepatocellular carcinoma, Subjects will start SBRT for one or more primary cancers and/or metastatic lesions and no more than 5 sites within two month before and after the start date of atezolizumab-bevacizumab combination therapy. In this study, it is expected to improve the treatment response rate of atezolizumab-bevacizumab therapy, which is currently first-line chemotherapy but has a low treatment response rate.
Detailed description
The subjects with advanced hepatocellular carcinoma who are indicated for the first-line atezolizumab-bevacizumab combination therapy are the primary subjects, and if they voluntarily agree to the clinical trial after explanation of the clinical trial, they are included in the clinical trial. Subjects should begin SBRT(stereotactic body radiotherapy) to one or more but not more than five sites for primary cancer and/or metastatic lesions within two month before and after the start date of atezolizumab-bevacizumab combination therapy. The followings are evaluation items for each visit. Visit 1 (-6\ 0 weeks) ± 7days \*Screening * Informed consent form * Inclusion Criteria/ Exclusion Criteria * Medical history and physical examination * Staging via CT, MRI, PET-CT, etc. (PET-CT examination is not compulsory) * CBC, SMA, PT/aPTT, Tumor markers, Biomarkers * Stool microbiota NGS * QoL Questionnaire(EORTC-QLQ-C30 V3) Visit 2 (0\ 7 weeks) ± 7 days \*During SBRT * Confirmation of adverse events * QoL Questionnaire(EORTC-QLQ-C30 V3) Visit 3 (1\ 8 weeks) \*1 week after SBRT * Confirmation of adverse events * CBC, SMA, PT/aPTT, Tumor markers, Biomarkers * QoL Questionnaire(EORTC-QLQ-C30 V3) Visit 4 (6\ 9 weeks) ± 7 days \*After 2 cycles of chemotherapy * Confirmation of adverse events * CBC, SMA, PT/aPTT, Tumor markers, Biomarkers * Stool microbiota NGS * QoL Questionnaire(EORTC-QLQ-C30 V3) Visit: 5\ 12 (3\ 36 months) ± 2 weeks \*Follow-up * Confirmation of adverse events * Evaluation of effectiveness\* (Imaging tests, Tumor markers, CBC, SMA, PT/aPTT are performed according to the need) * QoL Questionnaire(EORTC-QLQ-C30 V3)
Interventions
RADIATIONStereotactic body radiotherapy
Patients with advanced hepatocellular carcinoma who are indicated for the first-line atezolizumab-bevacizumab combination therapy are the primary subjects, and they should begin stereotactic radiotherapy to one or more but not more than five sites for primary cancer and/or metastatic lesions within two month before and after the start date of atezolizumab-bevacizumab combination therapy.
Sponsors
Yonsei University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Patients with advanced hepatocellular carcinoma who are indicated for the first-line atezolizumab-bevacizumab combination chemotherapy should begin stereotactic body radiotherapy to one or more but not more than five sites for primary cancer and/or metastatic lesions.
Intervention model description
Patients with advanced hepatocellular carcinoma who are indicated for the first-line atezolizumab-bevacizumab combination chemotherapy should begin stereotactic body radiotherapy to one or more but not more than five sites for primary cancer and/or metastatic lesions.
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 19 to 80 years old 2. Liver function Child-Pugh class A 3. ECOG 0-1 4. Patient clinically or pathologically diagnosed with hepatocellular carcinoma 5. Advanced hepatocellular carcinoma that is inoperable 6. Satisfies the dose limits for normal organs and lesions of an appropriate size to be included in the scope of radiotherapy.
Exclusion criteria
1. Brain metastases 2. Have a history of malignancy other than hepatocellular carcinoma within the last 5 years (except for malignancies with little risk of metastasis or death, e.g., adequately treated cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, tubular carcinoma in situ, or stage 1 uterine cancer.) 3. Subjects with a high probability of untreated gastric or esophageal varices or bleeding 4. Serious uncontrolled medical comorbidities 5. History of liver transplant surgery 6. Autoimmune liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival at 6 month | 6 months after registration | The primary endpoint is to improve 6-month progression-free survival rate in the treatment group compared to those existing literature. Progression-free survival and overall survival are evaluated using the Kaplan-Meier curve. Verified through one sample proportion test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 36 months after registration | Progression-free survival and overall survival are evaluated using the Kaplan-Meier curve. Verified through one sample proportion test. |
| Objective response rate | 36 months after registration | Objective response rate will be ratepresented as a proportion of the total. |
| Adverse event (Toxicity) | 36 months after registration | Toxicity will be evaluated using CTCAE version 5.0 and presented as a proportion of the total. |
| Tumor marker response: AFP, PIVKA-II | 36 months after registration | Tumor markers and biological markers are descriptive as statistics such as mean, standard deviation, and median for continuous data will be presented, and changes in values before and after treatment will be compared and evaluated using paired t-test or Wilcoxon signed rank test. |
Countries
South Korea
Contacts
Primary ContactHwakyung BYUN, Phd
Outcome results
None listed