A Pilot Study of Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma

This is a pilot single arm study with the primary endpoints of feasibility and preliminary estimates of safety and efficacy. This protocol builds on over 25 years of experience with high dose liver RT (Radiation Therapy), and in particular adaptive RT aimed at adjusting the global radiation dose based on a patient's measured sensitivity to treatment. This current protocol uses functional imaging and specialized radiation planning techniques to spare highly functional portions of the liver to preserve function. The investigators feel this will further improve the safety and efficacy of RT for all patients by customizing treatments to each. If this approach is promising, the investigators will proceed to a phase II randomized study of standard versus spatially and dosimetrically adapted RT.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Radiation: Adaptive Radiation Therapy

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48187
      • Rogel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients must have hepatocellular carcinoma.
• Patients must not have extrahepatic cancer.
• Patients must not be eligible for a curative liver resection or have refused resection
• Patients must have recovered from the acute effects of prior liver-directed therapy and 4 weeks must have passed since the last procedure and protocol therapy.
• Patients must have a Zubrod performance status of less than or equal to 2 (Zubrod performance status is a measure that attempts to quantify a cancer patients' general well-being. Scores run from 0 to 5 where 0 denotes normal activity and 5 denotes death).
• Patients must be 18 years of age or older.
• Patients must have adequate organ function.
• Patients must understand and be willing to sign an IRB (Institutional Review Board) approved informed consent form.

Exclusion Criteria:

• Patients with known allergies to intravenous iodinated contrast agents.
• Patients with a contraindication to contrast-enhanced MRI are excluded.

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: Adaptive Radiation Therapy	Radiation: Adaptive Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Local Progression	The primary efficacy endpoint is local control, measured as the duration of time from start of treatment to time of progression of the treated (target) lesion(s). Patients with no evidence of local progression at the time of data analysis will be censored at the last date on which they were evaluated for local progression. Local progression will be summarized with Kaplan-Meier curves and reported with 95% confidence intervals.	24 months
The Proportion of Patients for Whom the Intended Treatment Was Feasible	The primary aim of the trial is feasibility which is defined as the ability to successfully deliver the full treatment including all adaptations and in particular the perfusion-based planning and replanning.	At end of treatment; up to ~3 months
Percentage of Patients With Change in Child Pugh Score >= 2	Rate of liver decompensation reported as the percentage of patients with a change in Child Pugh score of greater than or equal to 2 within 6 months of SBRT.	Baseline to approximately 6 months after initiation of SBRT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Progression	Defined as the duration of time from start of treatment to time of progression.	24 months
Overall Survival	Overall survival (OS) is defined as the duration of time from start of treatment to death.	24 months
Change in ALBI Scores	Liver decompensation assessed by change in ALBI score > 0.5 from baseline.	Approximately 6 months
Incidence of Grade 3 Gastrointestinal (GI) Bleeding Toxicities	Grade 3 GI bleeding assessed via the NCI CTCAE version 4.0.	Approximately 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Radiation Induced Liver Disease (RILD)	RILD is a rare but serious side effect that will be summarized if it occurs.	24 months

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Theodore Lawrence, M.D., Ph.D., Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2016
• Primary Completion (Actual): January 20, 2022
• Study Completion (Actual): January 20, 2022

Study Registration Dates

• First Submitted: May 28, 2015
• First Submitted That Met QC Criteria: May 29, 2015
• First Posted (Estimated): June 2, 2015

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: UMCC 2015.039; HUM00098022 (Other Identifier: University of Michigan)