Clinical Trial Comparing TACE With TACE + SABR in Stage BCLC B HCC (HepSTAR)

Phase 2TerminatedNCT02958163

Cliniques universitaires Saint-Luc- Université Catholique de Louvain3 enrolled

Overview

This will be multicentre a phase II randomized controlled and open-label trial. It will compare the 6-months objective response (CR+PR) rates obtained with Drug Eluting Bead Trans-Arterial Chemo-Embolization (DEB-TACE) alone versus DEB-TACE followed by Stereotactic Ablative Radiotherapy (SABR) in patients with hepatocarcinoma stage BCLC B. This trial will also include one substudy. This substudy will confront the immuno-histochemical results collected on tumoral biopsies to the biological and imaging (MRI) results. Every patient participating to the trial can also participate to this substudy.

The patients will be randomized in 2 arms determining the treatment they will receive: Arm A: actual standard treatment = TACE Arm B: experimental arm = TACE + SABR

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Liver Neoplasms Hepatocellular Cancer

Interventions

Stereotactic Ablative RadiotherapyRADIATION

SABR schemes will be adapted according to the CP score and the vicinity of surrounding organs at risk. These are the different schemes proposed in this trial: 48Gy = 3x16Gy BED 124.8Gy ( α/β=10) 50Gy = 5x10Gy BED 100Gy ( α/β=10) 48Gy = 6x8Gy BED 86.4Gy ( α/β=10) 40Gy = 5x8Gy BED 72Gy ( α/β=10) For patients with Child-Pugh (CP) A cirrhosis : the choice of the scheme will be left to each physician. The highest BED should be favored if dose constraints to the organs at risk are respected. For patients with CP B cirrhosis : only the latter scheme will be allowed: 40Gy = 5x8Gy.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Hepatocellular carcinoma larger than 3 cm and non-resectable, with a diagnosis established either by: * dynamic imaging (non-invasively), showing a typical contrast enhancement and wash-out * histopathology * satellite lesions are allowed (at most three lesions) as long as the doses constraints are still achievable * Hepatocellular carcinoma belonging to Barcelona Clinic Liver Cancer Stage System class B * Tumor must be measurable on a multi-phase MRI according to mRECIST criteria * Non-tumoral liver volume ≥ 800 cc * Child-Pugh (CP) A to B7 cirrhosis * HCC Patients can be included if they require treatment prior to liver transplantation * ECOG performance status 0-1 * AST/ALT \< 5 times ULN * Initial platelets ≥ 50 000 x 10E9/l, neutrophils \> 1500 x 10E9/l, Hb \> 9 g/dl * Serum creatinine \< 1.5 X normal, or calculated Creatinine clearance rate ≥ 60 mL/min * As tumor biopsy can be performed after inclusion, pure hepatocellular carcinoma but also mixed hepatocellular carcinoma will be allowed in this trial. Cholangiocarcinoma cannot be included. * Written informed consent form to be signed, * Patient willing and able to comply to the follow-up schedule * Patients in fertile age should use a contraceptive method during treatment and 4 months after. Exclusion Criteria: * Eligibility for resection or ablative treatments * Extra hepatic spread of the disease * Previous treatment of the same lesion with TACE * Previous treatment with selective internal radiotherapy or radiotherapy to the upper abdomen * Uncontrolled Ascites * Uncontrolled Encephalopathy * Any clinical sign of acute viral or non-viral hepatitis (new serological testing are not required) * Known current pregnancy * Uncontrolled active co-morbidity

Locations (5)

Hôpital de JOLIMONT

Jolimont, Hainaut, Belgium

Centre Hospitalier Universitaire/CHC Saint Joseph

Liège, Liège, Belgium

Cliniques Universitaires Saint Luc

Brussels, Woluwé Saint Lambert, Belgium

Institut Jules Bordet/Hôpital Erasme

Brussels, Belgium

Clinique et Maternité Sainte Elisabeth/CHU Mont Godinne

Namur, Belgium

Outcomes

Primary Outcomes

Objective response rate at 6 months

Objective response rate including complete and partial response based on the MRI evaluation (mRECIST)

Time frame: 6 months after the completion of treatment

Secondary Outcomes

Time to progression

defined as the time between the end of treatment and the occurrence of a local recurrence. The diagnoses of another intra- or extra-hepatic lesion of HCC will not be considered as progression

Time frame: 1 year after the treatment completion

Time to untreatable progression

defined as the time between the end of treatment and the occurrence of untreatable intra-hepatic disease

Time frame: 1 year after the treatment completion

6-months overall survival

defined as survival rate of patients at 6months after the end of treatment

Time frame: 1 year after the treatment completion

1-year overall survival

defined as survival rate of patients at 1 year after the end of treatment

Time frame: 1 year after the treatment completion

Acute toxicities

Acute toxic events will have to be described and recorded in accordance with the CTCAE 4.03 (Common Terminology Criteria for Adverse events).

Time frame: 6 months after treatment completion

Late toxicities

Late toxic events will have to be described and recorded in accordance with the CTCAE 4.03 (Common Terminology Criteria for Adverse events).

Time frame: 6 months after treatment completion

Quality of life assessment by questionnaire at baseline

Quality of life will be assessed by questionnaires: EORTC QLQC30. The investigators will ask each patient to answer to these questionnaires once at randomization.

Time frame: baseline

Quality of life assessment by questionnaire at 2 months

Quality of life will be assessed by questionnaires: EORTC QLQC30. The investigators will ask each patient to answer to these questionnaires 2 months after treatment completion

Time frame: 2 months

Quality of life assessment by questionnaire at 6 months

Quality of life will be assessed by questionnaires: EORTC QLQC30. The investigators will ask each patient to answer to these questionnaires 6 months after treatment completion

Time frame: 6 months after treatment completion

Assessment by questionnaires of specific for hepatocarcinoma quality of life at baseline

Quality of life will be assessed by questionnaires specific for patients with hepatocarcinoma:EORTC QLQH18. The investigators will ask each patient to answer to these questionnaires once at randomization.

Time frame: baseline

Assessment by questionnaires of specific for hepatocarcinoma quality of life at 2 months

Time frame: 2 months after treatment completion

Assessment by questionnaires of specific for hepatocarcinoma quality of life at 6 months

Time frame: 6 months after treatment completion

Overall response rate based on the MRI evaluation in Child Pugh B7 patients

As the choice of the irradiation scheme will be influenced by the severity of the underlying cirrhosis with a Child Pugh score B7, the overall response rate in this specific kind of patients will be separately measured besides the overall response rate of the whole cohort.

Time frame: 6 months