A Pilot Trial of Stereotactic Body Radiation Therapy (SBRT) to Induce Tumor Hyperemia in Combination With Transarterial Chemoembolization (TACE) for Unresectable Hepatocellular Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Child-Pugh Class A
- Sponsor
- Ohio State University Comprehensive Cancer Center
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Feasibility of SBRT in combination with TACE, measured by the number of patients able to tolerate all study procedures
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This pilot clinical trial studies stereotactic body radiation therapy (SBRT) and transarterial chemoembolization (TACE) in treating patients with liver cancer that cannot be removed by surgery. SBRT is a specialized radiation therapy that delivers a high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Chemoembolization kills tumor cells by carrying drugs directly into blood vessels near the tumors and then blocking the blood flow to allow a higher concentration of the drug to reach the tumor for a longer period of time. SBRT may make TACE more beneficial by increasing blood flow to the tumor, which may allow more of the TACE chemotherapy to enter the tumor. Giving SBRT with TACE may work better in treating patients with liver cancer that cannot be removed by surgery.
Detailed Description
PRIMARY OBJECTIVES: I. To establish the feasibility of completing SBRT followed by TACE in a 2 day time period. SECONDARY OBJECTIVES: I. To determine acute tumor perfusion changes after SBRT using functional magnetic resonance imaging (MRI) (magnetic resonance \[MR\]-dynamic contrast enhanced \[DCE\]/perfusion weighted imaging \[PWI\], MR-diffusion, blood oxygen level dependent \[BOLD\] sequences). II. To establish safety and tolerability of this regimen. III. To determine overall response rates (using modified Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria), including objective response rate (partial response \[PR\] + complete response \[CR\]) and clinical benefit rate (stable disease \[SD\] + PR + CR) at 1, 3, and 6 months after TACE. IV. To evaluate local control, progression-free survival, and overall survival at 1, 3, 6, 9, and 12 months after a single-dose of SBRT followed by TACE. V. To correlate micro ribonucleic acid (miRNA) biomarkers with response and toxicity. OUTLINE: This is a dose-escalation study of SBRT. Patients undergo SBRT on day 1 and TACE on day 2. After completion of study treatment, patients are followed up at 1-2 weeks and at 1, 3, 6, 9, 12, 18, and 24 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have a diagnosis of hepatocellular carcinoma by at least one criterion listed below:
- •Histologically confirmed
- •Magnetic resonance imaging (MRI) or computerized tomography (CT) findings consistent with hepatocellular carcinoma
- •Alpha fetoprotein (AFP) \> 400 ng/mL AND evidence of at least one solid liver lesion \> 2 cm regardless of specific imaging characteristics on CT or MRI
- •Patients must be non-transplantable, unresectable, or medically inoperable and eligible for TACE as determined by a multi-disciplinary team
- •Absolute neutrophil count \>= 1.5 × 10\^9/L
- •Hemoglobin \>= 9 g/dl
- •Platelets \>= 50,000/mm\^3
- •Prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (PTTa) =\< 1.5
- •Albumin \>= 2.5 g/dL
Exclusion Criteria
- •Childs-Pugh C liver function
- •Major liver vascular invasion
- •Prior radiation to the liver or other upper abdominal regions
- •Must not have any evidence of bleeding diathesis or active gastrointestinal bleeding
- •Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, or carcinoma in situ of the cervix; patients with a previous malignancy without evidence of disease for \>= 3 years will be allowed to enter the trial
- •History of active connective tissue disease (scleroderma)
- •Subjects who are breast-feeding, or have a positive pregnancy test will be excluded from the study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Medical contraindication to MR imaging (e.g. pacemakers, metallic implants, aneurysm clips, known contrast allergy to gadolinium contrast, pregnancy, nursing mothers, weight greater than 350 pounds)
- •Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator; this could include severe, active co-morbidities such as:
- •Uncontrolled cardiac disease (hypertension, unstable angina, myocardial infarction within last 6 months, uncontrolled congestive heart failure, cardiomyopathy with decreased ejection fraction)
Outcomes
Primary Outcomes
Feasibility of SBRT in combination with TACE, measured by the number of patients able to tolerate all study procedures
Time Frame: 2 days
Determined on the intent-to-treat principle. Any treatment delivery difficulties that arise that could impede successful delivery of this therapy sequence will be evaluated. The capability of the Ohio State University (OSU) system and communication between departments will be analyzed and deemed effective if it facilitates the successful treatment completion of all patients.
Secondary Outcomes
- Change in hypoxia measurements(Baseline to day 1 post-SBRT)
- Incidence of toxicities(Up to 30 days)
- Objective response rate (CR + PR) as measured by modified RECIST criteria version 1(Up to 6 months)
- Change in perfusion(Baseline to day 1 post-SBRT)
- Local control(Up to 12 months)
- Progression-free survival(Up to 12 months)
- Change in diffusion(Baseline to day 1 post-SBRT)
- Overall survival(Up to 12 months)