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

Liver Neoplasms Clinical Trial

— HepSTAR  

Official title:

Randomized Controlled Phase II Trial Comparing Trans-Arterial Chemo-Embolization (TACE) With TACE Plus Stereotactic Ablative Radiotherapy (SABR) in Stage BCLC B Hepatocarcinoma (HepSTAR)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02958163
• Other study ID #: 28248368
• Status: Terminated
• Phase: Phase 2
• First received: October 26, 2016
• Last updated: November 6, 2017
• Start date: February 20, 2017
• Est. completion date: October 17, 2017

Study information

• Verified date: March 2017
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 17, 2017
• Est. primary completion date: October 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatocellular Cancer
• Liver Neoplasms

Intervention

Procedure:
• Trans-arterial Chemo-Embolization
Trans-Arterial Chemo-Embolization will be performed with Doxorubicin-Eluting-Beads (DEB-TACE). It will be performed in each arm of treatment.

Drug:
• Doxorubicin
Drug-eluting Bead for Trans Arterial Chemo-Embolization will be loaded with Doxorubicin.

Radiation:
• Stereotactic Ablative Radiotherapy
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 ( a/ß=10) 50Gy = 5x10Gy BED 100Gy ( a/ß=10) 48Gy = 6x8Gy BED 86.4Gy ( a/ß=10) 40Gy = 5x8Gy BED 72Gy ( a/ß=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.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint Luc	Brussels	Woluwé Saint Lambert
Belgium	Institut Jules Bordet/Hôpital Erasme	Brussels
Belgium	Hôpital de JOLIMONT	Jolimont	Hainaut
Belgium	Centre Hospitalier Universitaire/CHC Saint Joseph	Liege	Liège
Belgium	Clinique et Maternité Sainte Elisabeth/CHU Mont Godinne	Namur

Sponsors (6)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain	Centre Hospitalier Universitaire Dinant Godinne - UCL Namur, Clinique Saint Joseph, Liège, Erasme University Hospital, Jules Bordet Institute, University Hospital of Liege

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immuno-histochemical detection of tumoral markers on biopsy (AFP/CK19/DCP)	Differents markers will be checked on biopsy (AFP = alpha foetoprotein/ CK19 = cytokeratin 19/ DPC= Des Carboxy prothrombin).	at time of biopsy
Other	Baseline biological detection of tumoral marker(s) : AFP +/- DCP	Biological detection of tumoral marker(s) will be done for every patient included in this trial (at least for AFP = alpha fetoprotein) at baseline then repeated every 2 months after treatment, up to 6 months. Measurement of DCP (Des-Carboxy-prothrombin will not be mandatory).	at baseline
Other	Biological detection of tumoral marker(s) (AFP +/- DCP) at 2 months after treatment	Biological detection of tumoral marker(s) will be done for every patient included in this trial (at least for AFP = alpha fetoprotein) at baseline then repeated every 2 months after treatment, up to 6 months. Measurement of DCP (Des-Carboxy-prothrombin will not be mandatory).	2 months after treatment completion
Other	Biological detection of tumoral marker(s) (AFP +/- DCP) at 4 months after treatment	Biological detection of tumoral marker(s) will be done for every patient included in this trial (at least for AFP = alpha fetoprotein) at baseline then repeated every 2 months after treatment, up to 6 months. Measurement of DCP (Des-Carboxy-prothrombin will not be mandatory).	4 months after treatment completion
Other	Biological detection of tumoral marker(s) (AFP +/- DCP) at 6 months after treatment	Biological detection of tumoral marker(s) will be done for every patient included in this trial (at least for AFP = alpha fetoprotein) at baseline then repeated every 2 months after treatment, up to 6 months. Measurement of DCP (Des-Carboxy-prothrombin will not be mandatory).	6 months after treatment completion
Other	MRI description of tumors at the hepatobiliary phase at baseline	immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected	at baseline
Other	MRI description of tumors at the hepatobiliary phase at 2 months after treatment	immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected	2 months after treatment completion
Other	MRI description of tumors at the hepatobiliary phase at 6 months after treatment	immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected	6 months after treatment completion
Primary	Objective response rate at 6 months	Objective response rate including complete and partial response based on the MRI evaluation (mRECIST)	6 months after the completion of treatment
Secondary	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	1 year after the treatment completion
Secondary	Time to untreatable progression	defined as the time between the end of treatment and the occurrence of untreatable intra-hepatic disease	1 year after the treatment completion
Secondary	6-months overall survival	defined as survival rate of patients at 6months after the end of treatment	1 year after the treatment completion
Secondary	1-year overall survival	defined as survival rate of patients at 1 year after the end of treatment	1 year after the treatment completion
Secondary	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).	6 months after treatment completion
Secondary	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).	6 months after treatment completion
Secondary	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.	baseline
Secondary	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	2 months
Secondary	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	6 months after treatment completion
Secondary	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.	baseline
Secondary	Assessment by questionnaires of specific for hepatocarcinoma quality of life at 2 months	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 2 months after treatment completion	2 months after treatment completion
Secondary	Assessment by questionnaires of specific for hepatocarcinoma quality of life at 6 months	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 6 months after treatment completion	6 months after treatment completion
Secondary	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.	6 months