18F-FDG PET in HCC Patients Candidate to Treatment With Sorafenib

Completed

• Conditions: HCC

• Registration Number: NCT02977754
• Lead Sponsor: Istituto Clinico Humanitas

Brief Summary

The principal objective of this study is to explore the role of 18F-FDG PET in identifying sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease outcome in advanced HCC patients candidate to systemic treatment with sorafenib.

Detailed Description

Aerobic glycolysis also called "Warburg effect", represents one of the distinctive hallmarks of the malignant cells. Although energetically less efficient than respiration, fermentative metabolism is advantageous for cell growth due to the increased availability of anabolic intermediates and the reduced cell dependence on oxygen. Moreover, by increasing intracellular reducing equivalents and decreasing mitochondria-derived ROS, glycolysis protects malignant cells from oxidant-induced senescence and apoptosis.

In diagnostic imaging, the "Warburg effect" is visualized thanks to the utilization of fluoro-2-deoxyglucose, a glucose analogue, labeled with the positron emitting nuclide fluoride-18 (18F). F-2-fluoro-2-deoxyglucose (18F-FDG) with positron emission tomography (PET) has emerged useful in many tumor types and in HCC can help ruling out extra-hepatic metastases or sites of recurrent disease, and giving prognostic information. Considering the abovementioned premises, the investigators hypothesize a potential use of 18F-FDG PET for the early assessment of sorafenib-induced metabolic shift in HCC, especially in well-differentiated subtypes usually showing an uptake of the tracer not different or at least not sufficiently increased compared to the normal liver.

For these reasons the investigators decided to conduct an explorative study for the assessment of predictive and prognostic role of 18F-FDG PET in patients affected by advanced HCC and candidate to systemic treatment with sorafenib.

The principal objective of this study is to explore the role of 18F-FDG PET in identifying sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease outcome in advanced HCC patients candidate to systemic treatment with sorafenib.

More specifically the investigators will:

* compare 18F-FDG uptake in HCC lesions, identified as target lesions (diam. min. 2cm), at baseline, at 24 hours and 1 week after the first administration of sorafenib.

* correlate the patterns of 18F-FDG uptake in HCC lesions with objective tumor response assessed 8 weeks after the first administration of sorafenib according to mRECIST criteria.

* correlate the patterns of 18F-FDG uptake in HCC lesions with alpha-fetoprotein (AFP) variation at baseline, at 24 hours and 1 week after the first administration of sorafenib.

* correlate the patterns of 18F-FDG uptake in HCC lesions with progression-free survival (PFS) and overall survival (OS).

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-11-18
• Study First Submitted QC: 2016-11-26
• Study First Posted: 2016-11-30
• Primary Completion: 2018-12
• Study Completion: 2019-03
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-29
• Last Update Posted: 2020-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

• patients with an histological diagnosis of HCC and scheduled to undergo systemic treatment with sorafenib;
• obtained informed consent

Exclusion Criteria

• patients age <18 years
• pregnancy or breast-feeding;
• patients affected by other malignancies within the last 3 years, with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Early change of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib	Compare 18F-FDG uptake in HCC lesions at baseline and at 24 hours after the first administration of sorafenib.	Baseline parameters

Secondary Outcome Measures

Name	Time	Method
Change of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib	Compare 18F-FDG uptake in HCC lesions at baseline and 1 week after the first administration of sorafenib.	Variation of parameters
Predictive role of metabolic characteristics of HCC (i.e. SUVmax, SUVmean, MTV, TLG) lesions under Sorafenib	Correlate the patterns of 18F-FDG uptake in HCC lesions with objective tumor response assessed 8 weeks after the first administration of sorafenib according to mRECIST criteria	PET scan parameters compared to response
Prognostic role of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib	Correlate the patterns of 18F-FDG uptake in HCC lesions with progression-free survival (PFS) and overall survival (OS) assessed during a minimun of 12 months of follow up	PET scan parameters compared to outcome

Trial Locations

Locations (1)

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Milano, Italy