Stereotactic Radiation Therapy in Treating Patients With Advanced Liver Cancer

Feasibility of Hypofractionated Stereotactic Radiotherapy in Patients With Hepatocellular Carcinoma

This is a phase I trial studying the side effects and best dose of stereotactic radiation therapy (SRT) in treating patients with advanced liver cancer. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Radiation: stereotactic body radiation therapy

Detailed Description

This is a phase I trial studying the side effects and best dose of stereotactic radiation therapy (SRT) in treating patients with advanced liver cancer. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Participants must have pathologically confirmed hepatocellular carcinoma with at least one tumor with a maximum diameter of ≤ 8 cm and must have Karnofsky performance status ≥ 60% and a life expectancy of at least 12 weeks.

The primary objective is determining the safety of hypofractionated stereotactic radiotherapy in patients with advanced hepatocellular carcinoma by using toxicity profiles described in the Common Terminology Criteria for Adverse Events (CTCAE) V.3.0. Secondary objectives are determining the maximal tolerable SRT dose, objective tumor response rate, the value of 4-Dimensional Computed Tomography (4DCT) in liver cancer planning, and the value of breath gating in liver cancer stereotactic body radiotherapy (SBRT). After completion of study therapy, participants are followed at 1 and 3 months.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6805
      • University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed advanced hepatocellular carcinoma (HCC)
• Measurable disease, defined as ≥ 1 unidimensionally target lesion that can be accurately measured by CT scan or MRI according to RECIST and must have a maximum diameter ≤ 8 cm
• Child-Pugh class A-B cirrhotic status
• Karnofsky performance status 60-100%
• Life expectancy ≥ 12 weeks
• White blood cell count (WBC) ≥ 2,000/μL
• Platelet count ≥ 60,000/mm³
• Hemoglobin ≥ 8.5 g/dLINR ≤ 2.3
• More than 6 months since prior myocardial infarction
• Prior systemic chemotherapy allowed
• At least 6 weeks since prior non-radiation local therapy (e.g., surgery, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation)
• Concurrent therapeutic anticoagulation (e.g., warfarin or heparin) allowed provided that no prior evidence of underlying abnormality in Prothrombin time (PT/INR) and partial thromboplastin time (PTT) exists

Exclusion Criteria:

• No known central nervous system (CNS) tumors, including metastatic brain disease
• No malignancy within the past 3 years that is distinct in its primary site or histology from HCC, except for carcinoma in situ of the cervix, treated basal cell carcinoma, or superficial bladder tumors (i.e., Ta, Tis, and T1), or any other cancer that has been curatively treated > 3 years prior to study entry
• No renal failure requiring hemodialysis or peritoneal dialysis

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection > grade 2
  • New York Heart Association (NYHA) class II-IV congestive heart failure
  • Active coronary artery disease
  • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
  • Uncontrolled hypertension
• Condition that could jeopardize the safety of the patient or study compliance
• No history of variceal bleeding where the varices have not been eradicated or decompressed by shunt placement
• No condition that would prevent the patient from undergoing marker implantation
• Not pregnant or nursing/negative pregnancy test
• No substance abuse, medical, psychological, or social condition that may interfere with the patient's participation in the study or evaluation of the study results
• No prior radiotherapy to the liver

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypofractionated stereotactic radiotherapy (SRT); All patients who have had successful implantation of a liver marker will undergo a 4D CT scan for planning SRT. Following transfer to the treatment planning system, the CT scan may be correlated by imaging fusion with MRI for contouring integrated tumor volume (ITV). The planning target volume (PTV) will be defined as ITV plus individualized margins which are determined by a 4D CT scan. Novalis with 6MV photons will be used for imaging guided SRT. Cohorts of 3-6 patients will receive SRT at daily doses of 8, 10, 12, 14 Gy within 2 weeks. The starting daily dose level will be 10 Gy. The marker will be localized by orthogonal X-ray to ensure reproducibility. A continuous respiratory gating will be accomplished with ExacTrac Adaptive Gating system if the required planning target margin is larger than 1 cm based on the 4D CT data.

Radiation: stereotactic body radiation therapy; Undergo radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Safety of Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Hepatocellular Carcinoma	Toxicity as assessed by NCI CTCAE v3.0 (Adverse Events). Due to delayed toxicities attributable to radiotherapy, all toxicities observed within 1 month after SRT will be scored. Dose limiting toxicity (DLT) is defined as any of following toxicities, that is possibly, probably or definitely related to Stereotactic Radiation Therapy (SRT) occurring within 1 month from the start of treatment: grade 4 or 5 hepatic; grade 4 or 5 gastrointestinal; grade 4 or 5 thrombocytopenia; grade 4 hepatic liver enzyme elevations persisting for ≥ 5 days; any adverse event requiring interruption of therapy by ≥ 2 weeks (14 calendar days).	Up to 1 month after Stereotactic Radiation Therapy (SRT) treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response at 1-month Post SRT	Response rate from tumor measurement at 1-month post-SRT	Measured from first day of SRT to 1-month post SRT.

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Chi Lin, MD, PhD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2007
• Primary Completion (Actual): February 15, 2017
• Study Completion (Actual): February 15, 2017

Study Registration Dates

• First Submitted: February 1, 2008
• First Submitted That Met QC Criteria: February 1, 2008
• First Posted (Estimated): February 6, 2008

Study Record Updates

• Last Update Posted (Actual): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: advanced adult primary liver cancer; recurrent adult primary liver cancer; localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: 0337-07-FB; P30CA036727 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No