Randomized Trial Comparing Stereotactic Body Radiation Therapy to Microwave Ablation for the Treatment of Localized Hepatocellular Carcinoma

A Phase II Randomized Trial Comparing Stereotactic Body Radiation Therapy to Microwave Ablation for the Treatment of Localized Hepatocellular Carcinoma

This is a randomized phase II study comparing microwave ablation (MWA) and stereotactic body radiation therapy (SBRT) for localized hepatocellular carcinoma (HCC).

This trial will be the first prospective comparison of these modalities for the treatment of HCC and will provide critical information regarding which local ablative modality is most appropriate for which patients. This study will also provide important information regarding quality of life and liver function changes following these two different treatment modalities.

Study Overview

• Status: Withdrawn
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Radiation: Microwave Ablation (MWA); Radiation: Stereotactic Body Radiation Therapy (SBRT)

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • The 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:

• Patients with hepatocellular carcinoma (HCC) are eligible for this trial. HCC is defined as having at least one of the following:

  1. HCC diagnosed either on biopsy or based on standard imaging criteria on contrast enhanced CT or MRI (arterial enhancement with washout and pseudocapsule); or
  2. A discrete hepatic tumor(s) as defined by the Barcelona criteria10 for cirrhotic patients, >1 cm with arterial hypervascularity and venous or delayed phase washout on CT or MRI
  3. Presentation at multidisciplinary liver tumor board to assess eligibility for either SBRT or MWA
• Patients must have 1-2 intrahepatic foci of HCC and may not be candidates for refuse hepatic resection. Patients who are on the organ wait list for (orthotopic liver transplantation) OLT will be considered for this trial as a "bridge" to transplant.
• Patients with 1 focus of HCC will be eligible if their tumor is 3.5 cm or less in greatest diameter. Patients with 2 foci of HCC will be eligible if each lesion is 3.5 cm in diameter or less and the combined diameter of both lesions is 5 cm or less.
• The foci of HCC must be in an anatomic location amendable to treatment by both MWA and SBRT.
• The patient must have an ECOG performance status of ≤ 2 (Eastern Cooperative Oncology Group Performance Status is an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death).
• Patients must have recovered from the acute effects of prior liver-directed therapy (e.g., RT, RFA, MWA or TACE) and a minimum of 4 weeks must have passed since the last procedure and protocol therapy.

• Patients must have:

  1. Platelets ≥ 50,000/mm3
  2. Child Pugh class A liver function or class B7 (Appendix II)
  3. INR (international normalized ratio (for anticoagulant monitoring)) < 1.5
• The patient must have a life expectancy of at least 12 weeks
• The patient must be at least 18 years old
• Patients must sign an IRB approved informed consent form for this purpose indicating that they are aware of the investigational aspects of the treatment and the potential risks. They also must be able to understand and the willing to sign a written informed consent.

Exclusion Criteria:

• Patients who have received prior abdominal radiation
• Patients with 3 or more foci of HCC
• Patients whose HCC involves the local vasculature, regional lymph nodes or distant metastatic sites
• Patients with Child Pugh liver function worse than B7

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MWA; MWA will typically be administered in one ablation session during which time up to 2 tumors are treated.	Radiation: Microwave Ablation (MWA); MWA will typically be administered in one ablation session during which time up to 2 tumors are treated.
Experimental: SBRT; SBRT will be administered in five fractions of up to 10 Gy per fraction. SBRT will be administered 5-15 days per tumor.	Radiation: Stereotactic Body Radiation Therapy (SBRT); SBRT will be administered in five fractions of up to 10 Gy per fraction. SBRT will be administered 5-15 days per tumor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to local tumor progression	The primary outcome of this trial is to prospectively determine local control rates in patients with HCC treated with MWA or SBRT. Freedom From Local Progression (FFLP) is defined as the time from randomization to local tumor progression. Tumors falling to group PD (progressive disease) would constitute local control failures. Progressive disease will be defined as at least a 20% increase in the LD (longest diameter) of target lesion, taking as reference the smallest LD recorded. Or at least a 20% increase in viable arterial enhancing disease, taking as reference the smallest LD of viable HCC since treatment started. Increases of less than 3 mm compared to the smallest LD recorded will be considered stable disease rather than PD.	Patients will be followed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of gastrointestinal (GI) and hepatobiliary toxicity	The number of patients experiencing grade 3 or higher GI or hepatobiliary toxicity by Common Terminology Criteria for Adverse Events (CTCAE) v4.0.	Patients will be followed up to 2 years
Incidence of liver function worsening	The number of patients experiencing a 2 point or more increase in Child-Pugh score and an increase in albumin-bilirubin score of at least 0.5.	Patients will be followed up to 2 years
Change in FACT- Hep questionnaire score	The FACT-Hep questionnaire is used to measure health-related quality of life (HRQoL) in patients with hepatobiliary cancers. They are asked questions about their physical, social, emotional and functional well-being and asked to provide a score between 0 and 4 where 0 represents not at all and 4 represents very much.	Questionnaires will be administered pre-treatment, post-treatment, and at 1, 3 ,6, 9, 12, 15, 18, 21, and 24 months post-treatment
Overall survival time	Overall survival (OS) is defined as the time from randomization to death from any cause. Patients who are alive at last follow-up will be censored on that date.	Patients will be followed up to 2 years
Progression free survival time	Progression Free Survival (PFS) is defined as the minimum time to death or any progression.	Patients will be followed up to 2 years
Metastasis free survival time	Metastasis-free survival (MFS) is defined as the minimum time to development of metastases or death, whichever occurs first.	Patients will be followed up to 2 years
Incidence of intrahepatic failure	Intrahepatic failure will include progression of the treated lesion(s) as well as development of other new liver lesions.	Patients will be followed up to 2 years

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Dawn Owen, M.D., Ph.D., University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2017
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 24, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): June 25, 2018
• Last Update Submitted That Met QC Criteria: June 20, 2018
• Last Verified: June 1, 2018

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 2017.001; HUM00124501 (Other Identifier: University of Michigan)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No