Dose Escalation Study for Primary Hepatocellular Carcinoma (SBF-HCC)

November 15, 2018 updated by: Mark Langer, Indiana University School of Medicine

Multi-institution Phase I/II Dose Escalation Study of Hypofractionated Stereotactic Body Radiation Therapy for Primary Hepatocellular Carcinoma

The purpose of this study is to determine the maximum tolerated dose of limited fractions of large dose radiation in an effort to achieve a biologically potent cancer therapy in selected patients with primary hepatocellular carcinoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Despite recent advances in early detection and diagnosis, only 30-40% of patients with hepatocellular carcinoma may benefit from radical therapies. Liver transplantation offers the best chance for cure. Surgical resection has been the only other potentially curative option, but the majority of patients are not candidates for resection. This reflects the usual comorbidity of severe underlying liver disease that either precludes surgery or makes the surgical approach extremely dangerous.

Study Type

Interventional

Enrollment (Actual)

77

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Department of Radiation Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

Evaluation by the Surgery and/or Liver Transplant Team has been performed and the patient is not considered a candidate for either "standard" therapy to target area (upper abdomen)

  • Adequate liver function defined as:

    • total bilirubin < 3mg/dl, albumin > 2.5 g/dl
    • normal PT/PTT unless on anticoagulants
    • mild elevation of liver enzymes acceptable (must be less than three times upper limit of normal)
  • Adequate renal function (creatinine < 1.8 mg/dl or creatinine clearance ≥ 50 ml/min)

  • Adequate bone marrow reserve:

    • ANC count ≥ 1500 mm3
    • Platelets ≥ 50,000/mm3
    • Hemoglobin > 9 g/dL

NOTE: Lab values must be obtained within 2 weeks prior to being registered for protocol therapy.

Exclusion Criteria:

  • No history of systemic lupus erythematous, rheumatoid arthritis, systemic sclerosis or scleroderma
  • No chemotherapy within 14 days before radiotherapy (chemotherapy may cause transient hepatitis with hepatomegaly)
  • No subsequent chemotherapy planned within 2 weeks of radiotherapy
  • No active liver infection

  • No acute Hepatitis. Definition of active disease:

    • Hepatitis A: Acute hepatitis determined by presence of Anti-HAV- IgM

    • Hepatitis B:

      1. HBsAg (HB surface Antigen): present in patients with acute and chronic hepatitis
      2. HBV DNA present in patients with active viral replication in amounts greater than 100,000 copies
      3. HBeAg is present in wild type HBV infection and suggests active replication
      4. Anti-HBs: Antibody against HBsAg appears after HBV infections and confers immunity
      5. Anti-HBc-IgM: Antibody against HBcAg, fraction IgM, present in acute infection and often could be detected during periods of high viral replication in chronic disease
      6. Anti-HBc-IgG: is present in chronic disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radiation Treatment Arm :A
Patients with a score of Childs A Will receive 3 fractions of radiation over 5-10 days
Radiation: Stereotactic Body Radiation
Arm A: Childs A - receive 3 fractions. Arm B: Childs B - receive 5 fractions.
Other Names:
  • Stereotactic Body Radiation Treatments
Experimental: Radiation Treatment Arm: B
Patients with a score of Childs B will receive 5 fractions of radiation over 2-6 weeks.
Radiation: Stereotactic Body Radiation
Arm A: Childs A - receive 3 fractions. Arm B: Childs B - receive 5 fractions.
Other Names:
  • Stereotactic Body Radiation Treatments

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With DLTs
Time Frame: 6 weeks
Number of patients experiencing a Dose Limiting Toxicity during the Phase I portion of the trial.
6 weeks
6 Month Local In-field Control
Time Frame: 6 months
Percent of patients and the 95% Binomial Confidence interval who were free of in-field progression at 6 months following treatment for the patients in Phase II
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to In-field Failure
Time Frame: up to 4 yrs
Kaplan-Meier Analyses will be used to calculate the median and 95% Confidence Interval for the time until in-field failure. This will be calculated from the time of treatment until the time of in-field failure. If a patient did not have in-field failure, the patient will be censored at their last evaluation date.
up to 4 yrs
Overall Survival
Time Frame: Up to 8 years
Kaplan-Meier Analysis will be used to calculate the median and 95% CI for overall survival. This will be calculated from the time of treatment until death. If a patient did not die, the patient will be censored at their last known alive date.
Up to 8 years
Phase II: Number of Patients With Treatment Related Grade 3 or 4 Adverse Events
Time Frame: up to 4 years
Number of unique patients who had grade 3 or 4 adverse events that were possibly, probably or definitely related to study treatment.
up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University School of Medicine

Collaborators

University of Colorado, Denver

Investigators

  • Principal Investigator: Mark Langer, MD, Indiana University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (Actual)

December 31, 2016

Study Completion (Actual)

December 31, 2016

Study Registration Dates

First Submitted

October 21, 2005

First Submitted That Met QC Criteria

October 21, 2005

First Posted (Estimate)

October 25, 2005

Study Record Updates

Last Update Posted (Actual)

December 13, 2018

Last Update Submitted That Met QC Criteria

November 15, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0404-20 (1011003002)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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