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

Hepatocellular Carcinoma Clinical Trial

— KARCHER-1  

Official title:

A Pilot Study on the Feasibility and Tolerance of Neoadjuvant Hypofractionated, Stereotactic Body Radiation Therapy Prior to Surgical Resection of Uninodular Hepatocellular Carcinoma.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04587739
• Other study ID #: 2017_03
• Secondary ID: 2019-A01441-56
• Status: Recruiting
• Phase: Phase 1
• Start date: January 31, 2021
• Est. completion date: January 2024

Study information

• Verified date: July 2022
• Source: University Hospital, Lille
• Contact: Emmanuel Boleslawski, MD,PhD
• Phone: 320444260
• Email: emmanuel.boleslawski[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Combination Product:
• Surgery with Neoadjuvant stereotactic body radiation therapy
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).

Locations

Country	Name	City	State
France	Hop Claude Huriez Chu Lille	Lille

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intraoperative number of packed red blood cells transfused (if any).		Postoperative 90 days
Secondary	Toxicity of radiation therapy using the National Cancer Institute CTCAE v.5.0 criteria		Postoperative 90 days
Secondary	Duration of surgery.		Postoperative 90 days
Secondary	Volume of intraoperative blood loss		Postoperative 90 days
Secondary	Quality of life by EORTC QLQ-C30		between before and after stereotactic radiotherapy
Secondary	Intraoperative adverse events		Postoperative 90 days
Secondary	Postoperative severe and overall morbidity rate	defined using the Comprehensive Complication Index and graded with the Dindo-Clavien score	Postoperative 90 days
Secondary	Postoperative mortality rate.		Postoperative 90 days
Secondary	Correlation between radiological observations on preoperative imaging and pathological features on surgical specimen (like percentage of tumor necrosis).		Postoperative day 30.
Secondary	Actuarial overall survival and disease-free survival.		Postoperative 24 months