Clinical trial NCT04587739: Neoadjuvant Hypofractionated Stereotactic Body Radiation Therapy Prior to Surgery for Hepatocellular Carcinoma: a Feasibility Study.
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
Stereotactic body radiation therapy
Hepatectomy
Neoadjuvant therapy
Drop-out
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2020-10-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Drop-out rate
timeFrame: Five months after the inclusion of the last participating patient
Secondary outcomes:
measure: Intraoperative number of packed red blood cells transfused (if any).
timeFrame: Postoperative 90 days
measure: Toxicity of radiation therapy using the National Cancer Institute CTCAE v.5.0 criteria
timeFrame: Postoperative 90 days
measure: Duration of surgery.
timeFrame: Postoperative 90 days
measure: Volume of intraoperative blood loss
timeFrame: Postoperative 90 days
measure: Quality of life by EORTC QLQ-C30
timeFrame: between before and after stereotactic radiotherapy
measure: Intraoperative adverse events
timeFrame: Postoperative 90 days
measure: Postoperative severe and overall morbidity rate
timeFrame: Postoperative 90 days
measure: Postoperative mortality rate.
timeFrame: Postoperative 90 days
measure: Correlation between radiological observations on preoperative imaging and pathological features on surgical specimen (like percentage of tumor necrosis).
timeFrame: Postoperative day 30.
measure: Actuarial overall survival and disease-free survival.
timeFrame: Postoperative 24 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Hop Claude Huriez Chu Lille
Study officials:
affiliation: University Hospital, Lille
name: Emmanuel Boleslawski, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: