A National Phase II Study of Proton Therapy in Hepatocellular Carcinoma

May 10, 2023 updated by: University of Aarhus

350 new cases of hepatocellular carcinoma (HCC) are diagnosed in Denmark each year, but the overall prognosis is poor with a 1-year survival rate of less than 40% and a 5-year survival rate of 10% for the entire patient group.

This national phase II non-randomized single-arm study of proton therapy in HCC is conducted with the aim to offer a safe and efficient radiation treatment to fragile patients with reduced dose to the normal liver compared to conventional photon-based radiotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Each year, approximately 350 new cases of hepatocellular carcinoma (HCC) are diagnosed in Denmark, but the overall prognosis is poor with a 1-year survival rate of less than 40% and a 5-year survival rate of 10% for the entire patient group.

This national phase II non-randomized single-arm study of proton therapy in HCC is conducted with the aim to offer a safe and efficient radiation treatment to fragile patients with reduced dose to the normal liver compared to conventional photon-based radiotherapy. The study aims to offer curative treatment to a larger group of patients and thus better prognosis for these patients.

The study will include 50 patients enrolled within 3 years. Patients cannot be guaranteed any direct personal benefits of participating in the trial. Participating in the study can help with new knowledge that can benefit future patients with similar illness.

The treatment will be given at the Danish Center for Particle Therapy. During radiotherapy, additional CT scans will be performed weekly as part of quality assurance until it can be documented that there is no such need.

Participation in the study will also mean additional examinations and questionnaires at the start of treatment, below treatment and at follow-up.

All patients will be asked to supply blood samples to analyze for circulating tumor DNA.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Denmark
    • Hovedstaden
    • Midtjylland
      • Aarhus, Midtjylland, Denmark, 8200
        • Recruiting
        • Aarhus University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Hanna R Mortensen, MD
        • Principal Investigator:
          • Britta Weber, MD
        • Sub-Investigator:
          • Morten Høyer, MD
        • Sub-Investigator:
          • Gerda E Villadsen, MD
        • Sub-Investigator:
          • Peter Jepsen, MD
        • Sub-Investigator:
          • Esben Worm
        • Sub-Investigator:
          • Elizaveta Tabeksblat, MD
    • Syd
      • Odense, Syd, Denmark, 5000
        • Not yet recruiting
        • Odense University Hospital
        • Contact:
        • Contact:
          • Annette Fialla

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with HCC based on classical radiologic findings as defined by the American Association for the Study of Liver Diseases (AASLD) criteria or verified by biopsy
  • No extra-hepatic disease
  • Deemed ineligible for resection or Radiofrequency Ablation (RFA), or the patients should refuse RFA or surgery
  • Age ≥ 18 years
  • Performance status ≤ 2
  • Total diameter of tumor(s) ≤ 12 cm and a maximum of 3 tumors
  • Adequate liver function as measured by Child-Pugh score (Child-Pugh score ≤ 8), or absence of cirrhosis
  • Has recovered adequately from toxicity and/or complications from any previous local interventions
  • Patients with past or ongoing hepatitis C infection are allowed, but treatment for hepatitis C must have been completed one month before study entry
  • Patients with hepatitis B infection is allowed if antiviral therapy have been given for at least 4 weeks and Hepatitis B Virus (HBV) viral load is less than 100 IU/ml. The active therapy must continue throughout the radiation therapy. Patients who are Total hepatitis B core antibody (anti-HBc)(+), negative for Hepatitis B surface antigen (HbsAg) and negative or positive for Hepatitis B surface antibody (anti-HBs) with a HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis

  • Adequate organ function

    • hematological: hemoglobin ≥ 6 mmol/l, absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 50 x 109/L
    • hepatic: bilirubin ≤ 1.5 x ULN, alanin-aminotransferase (ALAT) ≤ 1.5 x ULN
    • renal: creatinine ≤ 1.5 x ULN
  • Ability to adhere to procedures for study and follow-up
  • Signed informed consent to participate
  • Final decisions on inclusion and treatment with proton therapy are at the discretion of the investigator

Exclusion Criteria:

  • Previous x-ray-based radiotherapy in the liver
  • Child Pugh score >8
  • Tumor less than 1 cm from any critical organs at risk (OAR) (duodenum, kidney, stomach, intestines).
  • Previous Selective internal radiation therapy (SIRT)
  • Episode of hepatic encephalopathy within the last 6 months
  • Uncontrolled ascites with need for drainage > 1 per month
  • Episode of bleeding esophageal varices within the past month. If active bleeding from esophageal varices has occurred, a gastroscopy should be performed 4 weeks after the bleeding episode to ensure maximum grade 1 varices.
  • Patients with metal implants where beam entrance through the metal implants cannot be avoided (not applicable for fiducial markers implanted for radiotherapy use)
  • Patients for whom it is not possible to produce a robust treatment plan following the technical guidelines (Appendix A)
  • Patients for whom it is not possible to implant fiducial markers e.g. due to insufficient coagulation of the blood.

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Proton Arm
All patients in the study will receive proton therapy with 67.5 Gray/15 fractions(fx) /5fx per week .
Radiation: Proton therapy
All patients will receive proton therapy 67.5Gy/15fx

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of deaths of any cause
Time Frame: 4 months after start of radiotherapy
Death of any cause
4 months after start of radiotherapy
Number of participants with Radiation-induced liver disease (RILD)
Time Frame: 4 months after start of radiotherapy
Worsening of the Child- Pugh score ≥2 or alanin-aminotransferase (ALAT) ≥5 upper normal limit (ULN)
4 months after start of radiotherapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of participants with RILD within 6 months of start of radiotherapy
Time Frame: 6 months after start of radiotherapy
Worsening of the Child- Pugh score ≥2 or ALAT ≥5 ULN
6 months after start of radiotherapy
Acute toxicity
Time Frame: 4 months after start of radiotherapy
Number of participants with Acute radiation-related toxicity grade 3 or higher measured by CTCAE v5.0
4 months after start of radiotherapy
Late toxicity
Time Frame: from 4 months until 60 months after start of radiotherapy
Number of participants with Late radiation-related toxicity grade 3 or higher measured by CTCAE v5.0
from 4 months until 60 months after start of radiotherapy
Radiation-induced hospitalization
Time Frame: within 4 months after start of radiotherapy
Number of days spend in the hospital due to radiotherapy toxicity
within 4 months after start of radiotherapy
Health-related Quality of Life C30
Time Frame: Until 60 months after start of radiotherapy
Health-related Quality of life measured by the EORTC QoL questionnaires C30
Until 60 months after start of radiotherapy
Quality of Life HCC-18
Time Frame: Until 60 months after start of radiotherapy
Health-related Quality of life measured by the EORTC QoL questionnaires HCC18
Until 60 months after start of radiotherapy
Local control
Time Frame: 3 years after start of radiotherapy
1- and 3-year local control
3 years after start of radiotherapy
Progression-free survival
Time Frame: 3 years after start of radiotherapy
1- and 3-year progression-free survival
3 years after start of radiotherapy
Overall survival
Time Frame: 3 years after start of radiotherapy
1- and 3-year overall survival
3 years after start of radiotherapy
Pattern of failure
Time Frame: Until 5 years after start of radiotherapy
Pattern of failure will be reported as number of patients with in-field failures in the clinical target volumen (CTV), in-field failures in the planning target volume (PTV), and out-of-field failures.
Until 5 years after start of radiotherapy
Technical feasibility
Time Frame: up to 5 years
the proportion of patients where it was possible to adhere to the guidelines of CTV dose coverage and tolerable normal tissue dose
up to 5 years
Reduction in mean liver dose
Time Frame: up to 5 years
calculated on a per patient basis, and median (and inter-quartile ranged) will be reported for the study population.
up to 5 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Aarhus

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Odense University Hospital
Aarhus University Hospital
Rigshospitalet, Denmark
University of Leeds
Herlev Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Britta Weber, MD PhD, Danish Center of Particle Therapy

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 13, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 21, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 24, 2022

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DCPT HCC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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