Neoadjuvant Hypofractionated Stereotactic Body Radiation Therapy Prior to Surgery for Hepatocellular Carcinoma: a Feasibility Study.

NCT04587739 | Recruiting Phase 1 DMC

• 2 other identifiers: 2017_032019-A01441-56
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is the fifth more common cancer in the world, with high mortality rates, due to the low number of patients who are eligible for therapy with curative intent, like surgical resection. Moreover, surgical resection is associated with a high risk of tumor recurrence, because of the tumor seeding through microscopic intrahepatic vessels that surround the tumor, the so-called "microvascular invasion". To adequately deal with this phenomenon, the surgeon has to perform either an 'anatomical' liver resection, which remove not only the tumor but also the whole corresponding vascular network, or a 'tumorectomy' with resection margins of at least 2 cm. Unfortunately, these principles cannot always be achieved due to underlying liver cirrhosis that is present in more than 80% of patients. Stereotactic body radiation therapy (SBRT) has been proven to efficiently necrotize or stabilize HCC nodules when surgery is not possible. Our hypothesis is that pre-treatment with SBRT prior to surgical resection of HCC might improve the results through the destruction of possible seeding in the peritumoral environment. Given the novelty of this therapeutic strategy, it is necessary to verify its feasibility and safety, prior to test its efficacy in patients with HCC. The KARCHeR-1 study aims at making sure that preoperative SBRT would not result in important delays or serious adverse events such as to cancel the planned surgical resection, in patients who otherwise could have benefited from it. This issue is commonly called 'drop-out'. Thirty patients are expected to be included in the KARCHeR-1 study, which would be in favor of continuing to evaluate this therapeutic strategy if less than 3 drop-outs occur, and would be immediately discontinued if 3 drop-outs occur. Other outcomes will also been studied, like intraoperative issues, postoperative morbi-mortality, pathological features on the surgical specimen and its correlation with preoperative imaging, and finally, tumor recurrence and survival.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Stereotactic body radiation therapy; Hepatectomy; Neoadjuvant therapy; Drop-out

Outcome Measures

Primary Outcomes (1)

• Drop-out rate

  Drop-out rate: proportion of patients in whom surgical resection cannot be achieved, due to (at least one of the following reasons): * serious adverse events related to radiation therapy (especially liver decompensation); * disease progression while receiving radiation therapy or awaiting surgery; * patient's death.

  Five months after the inclusion of the last participating patient

Secondary Outcomes (10)

• Intraoperative number of packed red blood cells transfused (if any).

  Postoperative 90 days

• Toxicity of radiation therapy using the National Cancer Institute CTCAE v.5.0 criteria

  Postoperative 90 days

• Duration of surgery.

  Postoperative 90 days

• Volume of intraoperative blood loss

  Postoperative 90 days

• Quality of life by EORTC QLQ-C30

  between before and after stereotactic radiotherapy

Study Arms (1)

Experimental group

EXPERIMENTAL

Combination Product: Surgery with Neoadjuvant stereotactic body radiation therapy

Interventions

Surgery with Neoadjuvant stereotactic body radiation therapy COMBINATION_PRODUCT

Stereotactic hypofractionated robotic radiation therapy (24-45 Gy / 3 fractions) followed after 4-6 weeks by conventional hepatectomy (either anatomical liver resection, or non-anatomical liver resection with intention to achieve a minimal 2 cm margin).

Experimental group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy-proven hepatocellular carcinoma or EASL/AASLD criteria
• Single nodule, 3 to 8 cm of largest diameter
• Hepatocellular carcinoma eligible for conventional liver resection with curative intent (R0), without preoperative portal vein embolization

You may not qualify if:

• Performance status \> 2
• Severe comorbidity with contraindication for either surgery or radiation therapy
• Decompensated liver cirrhosis (Child-Pugh B or C)
• Neoplastic portal vein thrombosis or extra-hepatic metastases
• Previous anticancer therapy within the last 5 years

Sponsors & Collaborators

• University Hospital, Lille: lead
• Ministry of Health, France: collaborator

Study Sites (1)

Hop Claude Huriez Chu Lille

Lille, 59037, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Emmanuel Boleslawski, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emmanuel Boleslawski, MD,PhD

CONTACT

320444260; emmanuel.boleslawski@chru-lille.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: October 14, 2020
• Study Start: January 31, 2021
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: December 23, 2025

Record last verified: 2025-09

Locations

FR (1)