Clinical trial NCT03338647: SBRT or TACE for Advanced HCC
Official title: Randomized Study of Stereotactic Body Radiation Therapy (SBRT) Versus Transarterial Chemoembolization (TACE) in Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Stereotactic body radiation therapy
transarterial chemoembolization
SBRT
TACE
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: International Atomic Energy Agency
First posted: 2017-11-09
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized study of stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) in locally advanced hepatocellular carcinoma.


Eligibility criteria: Inclusion Criteria:

* HCC (biopsy or radiological diagnostic (\>1 cm, enhancing in arterial phase and wash-out in later phases).
* Number of lesions: not more than 3 lesions
* Lesion size: up to 10 cm for a single lesion (and up to 10 cm cumulative diameter, if there is more than 1 lesion)
* Child-Pugh A or B (\<7) on examination within 6 weeks prior to study entry
* BCLC Stage A/B
* Must be fit (eligible) for SBRT and TACE
* Unsuitable/unwilling for resection or transplant or radiofrequency ablation (RFA) or if these options are not available
* Distance between GTV (lesion) and luminal structures (including esophagus, stomach, duodenum, small or large bowel) is \>10 mm
* All blood work obtained within 2 weeks prior to study entry with adequate organ function defined as follows:

  * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
  * Platelets ≥50,000 cells/mm3
  * Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
  * Total bilirubin \< 2 mg/dL
  * Prothrombin time/INR \< 1.4 (unless on Coumadin/Warfarin)
  * Albumin ≥ 28 g/L
  * AST (and ALT) \< 5 times ULN
  * Serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min
  * Left-ventricular ejection fraction \>50% (cardiac ejection fraction should be measured in case of history of cardio-vascular disease.
  * May have had previous surgery, ethanol injection and RFA to the liver

Exclusion Criteria:

* • Not suitable for clinical trial or follow-up

  * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (Note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible). No active cancer therapy.
  * Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE)

    * Non-enhancing HCC on CT or CT-angio or
    * Portal vein thrombosis/macroscopic venous invasion
  * Arterio-portal and arterio-venous fistulas observed on pre-study imaging (if it is found during the TACE, the fistula may be embolized before injection of the drug).
  * Evidence of metastatic disease including nodal or distant metastases.
  * Previous TACE or radiation to the liver (including SIRT)
  * Life-threatening condition (including untreated HIV and active hepatitis B/C)

    * Detectable HBeAg and HBV viral load \> 20,000 IU/mL or
    * HBeAg-negative chronic hepatitis B and HBV viral load \>2,000 IU/mL
    * If HBV-DNA copy is higher than 500 copies/ml, anti-viral therapy, such as Entecavir followed by observation for 2 weeks.
    * If anti-HCV antibody is positive (may be false positive) and increased HCV viral load indicating active disease. Active HCV should be treated sufficiently before inclusion in the study. Below 2 million copies per milliliter (mL) is related to chronic hepatitis C that does not need antiviral therapy.
    * Patients with active hepatitis B or C should be on treatment for at least 4 weeks before inclusion in the trial
  * On sorafenib or other antineoplastic drug therapy within 7 days before inclusion (not accepted until time of progression).
  * Pregnancy or women of childbearing potential require a negative pregnancy test within 28 days

Primary outcomes:
measure: Progression (total of local, intra- and extrahepatic)
timeFrame: 1 year
Secondary outcomes:
measure: Response
timeFrame: 3 months
measure: Local control of treated tumor
timeFrame: 1 year
measure: Intrahepatic failure
timeFrame: 1 year
measure: Extrahepatic failure
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
measure: Treatment related toxicity
timeFrame: 1 year
measure: Cost-benefit
timeFrame: 1 year
Other outcomes:
Locations:
city: Delhi
country: India
facility: Medanta
state: NCT
Study officials:
References: