A National Phase II Study of Proton Therapy in Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

A National Phase II Study of Proton Therapy in Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05203120
• Other study ID #: DCPT HCC
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2022
• Est. completion date: January 1, 2030

Study information

• Verified date: May 2023
• Source: University of Aarhus
• Contact: Britta Weber, MD PhD
• Phone: +4526236694
• Email: britta.weber[@]auh.rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 1, 2030
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Radiation:
• Proton therapy
All patients will receive proton therapy 67.5Gy/15fx

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus	Midtjylland
Denmark	Herlev Hospital	Herlev	Hovedstaden
Denmark	Odense University Hospital	Odense	Syd

Sponsors (6)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Herlev Hospital, Odense University Hospital, Rigshospitalet, Denmark, University of Leeds

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of deaths of any cause	Death of any cause	4 months after start of radiotherapy
Primary	Number of participants with Radiation-induced liver disease (RILD)	Worsening of the Child- Pugh score =2 or alanin-aminotransferase (ALAT) =5 upper normal limit (ULN)	4 months after start of radiotherapy
Secondary	Number of participants with RILD within 6 months of start of radiotherapy	Worsening of the Child- Pugh score =2 or ALAT =5 ULN	6 months after start of radiotherapy
Secondary	Acute toxicity	Number of participants with Acute radiation-related toxicity grade 3 or higher measured by CTCAE v5.0	4 months after start of radiotherapy
Secondary	Late toxicity	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
Secondary	Radiation-induced hospitalization	Number of days spend in the hospital due to radiotherapy toxicity	within 4 months after start of radiotherapy
Secondary	Health-related Quality of Life C30	Health-related Quality of life measured by the EORTC QoL questionnaires C30	Until 60 months after start of radiotherapy
Secondary	Quality of Life HCC-18	Health-related Quality of life measured by the EORTC QoL questionnaires HCC18	Until 60 months after start of radiotherapy
Secondary	Local control	1- and 3-year local control	3 years after start of radiotherapy
Secondary	Progression-free survival	1- and 3-year progression-free survival	3 years after start of radiotherapy
Secondary	Overall survival	1- and 3-year overall survival	3 years after start of radiotherapy
Secondary	Pattern of failure	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
Secondary	Technical feasibility	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
Secondary	Reduction in mean liver dose	calculated on a per patient basis, and median (and inter-quartile ranged) will be reported for the study population.	up to 5 years