Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Stereotactic Body Radiation Therapy and Transarterial Chemoembolization in Treating Patients with Liver Cancer That Cannot Be Removed by Surgery

Protocol: OSU-15032

Full Title

A Pilot Trial of Stereotactic Body Radiation Therapy (SBRT) to Induce Tumor Hyperemia in Combination with Transarterial Chemoembolization (TACE) for Hepatocellular Carcinoma

Purpose

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 sends x-rays directly to the tumor using smaller doses over several days 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.

Study Objective

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, 4-6 weeks, and at 3, 6, 9, 12, 18, and 24 months.

Are you eligible?

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) =< 1.5

Albumin >= 2.5 g/dL

Alkaline phosphatase < 5 x upper limit of normal (ULN)

Total bilirubin =< 2.0 mg/dL

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN

Creatinine =< 1.5 ULN OR calculated creatinine clearance >= 50 mL/min

Must have Childs-Pugh A or B liver disease

Patients must have no clinical signs of heart failure and meet New York Heart Association functional classification I or II defined as:

Class I – patients with no limitation of activities; they suffer no symptoms from ordinary activities

Class II – patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion

Must have 1-3 liver lesions amenable to SBRT with tumor size < 15 cm (single lesion or sum)

Must be able to undergo two MRI scans, one before study treatment begins and another shortly after SBRT

Patients with extrahepatic disease, portal hypertension, or bilobar disease are allowed

Within 2 weeks of registration: patients must have vital signs, history/physical examination, laboratory studies (complete blood count [CBC] with differential, chemistries including liver function tests, AFP, creatinine clearance [CrCl] assessment, pregnancy test if needed)

Life expectancy of at least 12 weeks in the opinion of investigator

Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed

Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14 days of the first administration of study treatment; urine human chorionic gonadotropin (HCG) is an acceptable pregnancy assessment

Women/men of reproductive potential must be counseled on contraception/abstinence while receiving the study treatment

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)

Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration

Hepatic insufficiency resulting in jaundice and/or coagulation defects

Liver Cancer Gastrointestinal Cancers