Preoperative Stereotactic Body Radiotherapy (SBRT) Followed by Hepatectomy for Centrally Located Hepatocellular Carcinoma: a Prospective, Single-center, Phase I Study

February 3, 2023 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

Hepatocellular carcinoma (HCC) is the sixth prevalent malignancy worldwide. Although surgical excision is considered the standard treatment for resectable HCC, a high rate of postoperative recurrence was observed after partial hepatectomy, with a marginal recurrence rate up to 30%. Narrow margin resection may be the most appropriate procedure for centrally located HCC because the premise for survival is the conservation of more normal liver parenchyma. Unfortunately, narrow margin resection has been reported to contribute to poor survival outcomes. However, no (neo)adjuvant therapy before (or after) hepatectomy is generally considered to be effective in reducing post-operative recurrence.

Radiotherapy (RT) has been well used in many solid malignant tumors as an (neo)adjuvant to surgical treatment, including HCC. SBRT has shown encouraging rates of local control for HCC. Compared with standard fractionation radiation, SBRT can achieve more precise delivery of high-dose radiation beams to the lesion, obtaining a much smaller target volume. Meanwhile, it could be finished in a short period which can bring more convenience to patients. Recently, several study and randomized controlled trials revealed the survival benefit of adjuvant RT (IMRT and SBRT) in patients with HCC. However, there are still lack of exploration for the efficacy of neoadjuvant SBRT. This study is to analyze the safety of preoperative SBRT followed by hepatectomy for centrally located hepatocellular carcinoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

15

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

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310009
        • Recruiting
        • The second affiliated hospital of zhejiang university school of medicine

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 to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Aged ≥18 years;
  2. Confirmed diagnosis of HCC. The diagnosis can be established radiographically by the criteria of the American Association for the Study of the Liver (AASLD), or by histologic diagnosis from the core biopsy;
  3. Centrally located hepatocellular carcinoma and medically fit to undergo surgery as determined by the Multiple Disciplinary Team (MDT);
  4. BCLC stage A
  5. No imaging evidence of direct invasion of stomach, duodenum, small intestine, large intestine or diaphragm of the intrahepatic lesions to be treated with radiotherapy;
  6. Child-Pugh class A and B7;
  7. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1;
  8. Willing to provide tissue from an excisional biopsy of a tumor lesion;
  9. For patients with active HBV: HBV DNA < 2000 IU/mL during screening, and have initiated anti-HBV treatment at least 7 days prior to SBRT and willingness to continue anti-HBV treatment during the study;
  10. Adequate organ and marrow function as defined below:

1)Marrow: absolute neutrophil count ≥1.5×109/L; platelets ≥50×109/L; hemoglobin ≥90g/L; 2)Liver: total bilirubin ≤3× institutional upper limit of normal (ULN); AST(aspartate aminotransferase) or ALT(alanine aminotransferase) ≤ 5× institutional ULN; albumin ≥29g/L; 3)Kidney: creatinine ≤ 1.5× institutional ULN or estimated glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 (according to the Cockcroft-Gault formula); 11. Women of childbearing potential must be willing to use a highly effective method of contraception for the course of the study through 30 days after radiotherapy. Female patient of childbearing potential should have a negative serum pregnancy test before 72h of her first treatment. Sexually active males must agree to use an adequate method of contraception starting with the treatment through 4 months after radiotherapy.

Exclusion Criteria:

  1. Have received local or systemic treatments in the past, including but not limited to TACE, immunotherapy, targeted therapy, radiotherapy, radiofrequency therapy, etc.;
  2. Severe bleeding tendency or coagulation dysfunction within the previous 6 months;
  3. Extrahepatic metastasis;
  4. Prior abdominal irradiation;
  5. Any major surgery within 1 months prior to enrolment;
  6. Known history of active Bacillus Tuberculosis (TB)
  7. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  8. Active infection requiring systemic therapy;
  9. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy;
  10. Known psychiatric or substance abuse disorders ;
  11. Pregnant or breastfeeding;
  12. Known history of human immunodeficiency virus (HIV: HIV 1/2 antibodies);
  13. Received a live vaccine within 30 days before radiotherapy.

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: neoadjuvant stereotactic body radiation therapy followed by hepatectomy
Experimental: Phase1(Cohort 1): neoadjuvant stereotactic body radiation therapy (24Gy/3Fr) followed by hepatectomy Experimental: Phase1(Cohort 2): neoadjuvant stereotactic body radiation therapy (30Gy/3Fr) followed by hepatectomy Experimental: Phase1(Cohort 3): neoadjuvant stereotactic body radiation therapy (36Gy/3Fr) followed by hepatectomy
Radiation: Neoadjuvant stereotactic body radiation therapy (Multiple ascending dose) followed by hepatectomy for centrally located hepatocellular carcinoma.
Neoadjuvant stereotactic body radiation therapy (Multiple ascending dose) followed by hepatectomy for centrally located hepatocellular carcinoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of radiotherapy followed by hepatectomy : Incidence of Treatment-Emergent Adverse events (CTCAE v5.0)
Time Frame: 3 months after resection
Safety and tolerability of radiotherapy followed by hepatectomy
3 months after resection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local recurrence free survival
Time Frame: from date of enrollment to date of first documented local recurrence. Assessed up to 12 months
Local recurrence free survival
from date of enrollment to date of first documented local recurrence. Assessed up to 12 months
Progression free survival
Time Frame: from date of enrollment to the date of first documented progression. Assessed up to 12 months
Progression free survival
from date of enrollment to the date of first documented progression. Assessed up to 12 months
Overall survival
Time Frame: from date of enrollment to the date of death from any cause. Assessed up to 12 months
Overall survival
from date of enrollment to the date of death from any cause. Assessed up to 12 months
Time to Progress
Time Frame: from date of enrollment to the date of progress. Assessed up to 12 months
Time to Progress
from date of enrollment to the date of progress. Assessed up to 12 months
Quality of life by EORTC QLQ-C30
Time Frame: through study completion, an average of 1 year
Quality of life by EORTC QLQ-C30
through study completion, an average of 1 year

Collaborators and Investigators

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

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

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)

November 1, 2022

Primary Completion (ANTICIPATED)

November 1, 2023

Study Completion (ANTICIPATED)

February 1, 2024

Study Registration Dates

First Submitted

October 18, 2022

First Submitted That Met QC Criteria

October 27, 2022

First Posted (ACTUAL)

October 28, 2022

Study Record Updates

Last Update Posted (ACTUAL)

February 6, 2023

Last Update Submitted That Met QC Criteria

February 3, 2023

Last Verified

September 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-0743

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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