A Study of Individualized Stereotactic Body Radiation Therapy (SBRT) for Intrahepatic Cancer

A Phase II Study of Individualized Stereotactic Body Radiation Therapy (SBRT) for Intrahepatic Cancer

This is a Phase II trial to characterize the safety and efficacy of individualized stereotactic body radiation therapy (SRBT) for patients who have had previous liver treatment or who have primary hepatocellular carcinoma (HCC).

Study Overview

• Status: Completed
• Conditions: Liver Cancer; Hepatocellular Cancer
• Intervention / Treatment: Radiation: individualized Stereotactic Body Radiation Therapy (SBRT)

Detailed Description

The trial endpoints are toxicity, survival and progression-free survival. DCE-MRI and plasma biomarkers will also be collected to explore their use as tools for treatment individualization in future trials. During the current trial, an indicator of liver function, indocyanine green (ICG), will be used to identify during treatment patients who are at excess risk for radiation-induced liver disease (RILD) so that their radiation dose may be reduced. The model used for individualization will be updated as trial data accrue, so this is an adaptive trial of an individualized therapy. The planned accrual is seventy (70) evaluable patients over three years.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5010
      • University of Michigan Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• over age 18
• life expectancy of at least 12 weeks
• Zubrod performance status of ≤2.
• biopsy proven hepatocellular carcinoma (HCC)
• liver metastases
• a discrete hepatic tumor(s) as defined by the Barcelona46 criteria - for cirrhotic patients, (1) 2 imaging studies showing hypervascular tumor > 2cm, or (2) single imaging study showing hypervascular tumor > 2cm with AFP ≥ 400 ng/mL
• a discrete hypervascular tumor present on two consecutive imaging studies (CT or MRI) with documented growth of > 1cm in diameter
• adequate organ function
• women and men not interested in pregnancy
• must be recovered from the effects of any prior surgery, radiation therapy, chemotherapy and the effects of Radiofrequency Ablation (RFA) or Transcatheter Arterial Chemo Embolization (TACE)
• minimum of 6 weeks following their last surgical procedure, radiation and chemotherapy.

Exclusion Criteria:

• cannot be eligible for a curative liver resection
• uncontrolled ascites clinically evident on physical exam
• known allergy to IC-Green
• known allergy to intravenous iodinated contrast agents
• patients with poor venous access
• patients with metastatic cancer with normal liver function who have not undergone previous liver directed therapy and a single tumor < 6 cm in size.

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: Liver cancer patients; The aim of this study is to determine the safety and effectiveness of individualized Stereotactic Body Radiation Therapy (SBRT) in patients who either (1) have had previous liver treatments, and/or (2) have primary hepatocellular carcinoma (HCC).

Radiation: individualized Stereotactic Body Radiation Therapy (SBRT); The individualized SBRT involves two treatment phases. The first phase of treatment involves receiving three fractions of SBRT, followed by a 1-month break and assessment of liver function with a blood test - Indocyanine Green (IC-Green). The second phase of treatment involves receiving two more fractions of SBRT, whose doses are adjusted to account for tolerance of the first phase of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients With Local Control at 1 Year Post Treatment	For this study, local control is defined as the lack of progressive local disease following CR (Complete Response) or PR (Partial Response), or lack of progressive local disease in patients with non-evaluable disease, who have no progressive elevation in serum tumor markers.	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients Alive Without Progression at 1 Year	Progression is defined as a greater than or equal to 20% growth of a lesion from the smallest lesion measurement	1 Year
The Percentage of Patients Alive at 1 Year		1 Year
The Number of Patients Who Experience Grade 4+ Hepatotoxicity	Grade 4 toxicities are life threatening toxicities that require urgent attention.	1 Year
The Number of Patients That Experience Grade 4+ Gastrointestinal Bleeding	Grade 4 toxicities are life threatening toxicities that require urgent attention.	1 Year

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Kyle Cuneo, MD, University of Michigan Rogel Cancer Center

Publications and helpful links

General Publications

• Feng M, Suresh K, Schipper MJ, Bazzi L, Ben-Josef E, Matuszak MM, Parikh ND, Welling TH, Normolle D, Ten Haken RK, Lawrence TS. Individualized Adaptive Stereotactic Body Radiotherapy for Liver Tumors in Patients at High Risk for Liver Damage: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jan 1;4(1):40-47. doi: 10.1001/jamaoncol.2017.2303.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: September 23, 2011
• First Submitted That Met QC Criteria: January 27, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Actual): March 9, 2017
• Last Update Submitted That Met QC Criteria: January 18, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: UMCC 2009-053; HUM00029467 (Other Identifier: University of Michigan Medical IRB)