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

Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain (Other)
Overall Status
Terminated
CT.gov ID
NCT02958163
Collaborator
Erasme University Hospital (Other), Jules Bordet Institute (Other), University of Liege (Other), Clinique Saint Joseph, Liège (Other), Centre Hospitalier Universitaire Dinant Godinne - UCL Namur (Other)
3
Enrollment
5
Locations
2
Arms
7.9
Actual Duration (Months)
0.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Trans-arterial Chemo-Embolization
  • Drug: Doxorubicin
  • Radiation: Stereotactic Ablative Radiotherapy
 Phase 2

Detailed 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

Study Design

Study Type:
Interventional
Actual Enrollment :
3 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Feb 20, 2017
Actual Primary Completion Date :
Oct 17, 2017
Actual Study Completion Date :
Oct 17, 2017

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Trans-Arterial Chemo-embolization (TACE)

Trans-arterial Embolisation will be performed with drug-eluting beads loaded with Doxorubicin. First session will be given within 4 weeks after randomization. 4-phase MRI will be performed every 2 months to assess the response. In case of insufficient response according to the MRI performed at 2 or 4 months, a second or third session of DEB-TACE will be allowed, according to the physician's choice. Once complete response is achieved, the follow-up period will start. The date of the last session of TACE corresponds to the treatment completion date.

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.
Other Names:
  • TACE

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

    		•
    Experimental: TACE+Stereotactic Ablative Radiotherapy

    The first part of the treatment, which is the DEB-TACE delivery, will be exactly the same than in arm A. The radiotherapy (SABR) will then start within 4 to 6 weeks after. Afterwards, 4-phase MRI will be performed every 2 months to assess the response. In case of insufficient response according to the MRI performed at 2 or 4 months, a second or third session of DEB-TACE will be allowed, according to the physician's choice. Once complete response is achieved, the follow-up period will start. The date of the last SABR fraction or the last session of TACE corresponds to the treatment completion date.

    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.
    Other Names:
  • TACE

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

    • 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 ( 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.
    Other Names:
  • SABR

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective response rate at 6 months [6 months after the completion of treatment]

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

    Secondary Outcome Measures

    1. Time to progression [1 year after the treatment completion]

      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

    2. Time to untreatable progression [1 year after the treatment completion]

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

    3. 6-months overall survival [1 year after the treatment completion]

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

    4. 1-year overall survival [1 year after the treatment completion]

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

    5. Acute toxicities [6 months after treatment completion]

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

    6. Late toxicities [6 months after treatment completion]

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

    7. Quality of life assessment by questionnaire at baseline [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.

    8. Quality of life assessment by questionnaire at 2 months [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

    9. Quality of life assessment by questionnaire at 6 months [6 months after treatment completion]

      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

    10. Assessment by questionnaires of specific for hepatocarcinoma quality of life at baseline [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.

    11. Assessment by questionnaires of specific for hepatocarcinoma quality of life at 2 months [2 months after treatment completion]

      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

    12. Assessment by questionnaires of specific for hepatocarcinoma quality of life at 6 months [6 months after treatment completion]

      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

    13. Overall response rate based on the MRI evaluation in Child Pugh B7 patients [6 months]

      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.

    Other Outcome Measures

    1. Immuno-histochemical detection of tumoral markers on biopsy (AFP/CK19/DCP) [at time of biopsy]

      Differents markers will be checked on biopsy (AFP = alpha foetoprotein/ CK19 = cytokeratin 19/ DPC= Des Carboxy prothrombin).

    2. Baseline biological detection of tumoral marker(s) : AFP +/- DCP [at baseline]

      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).

    3. Biological detection of tumoral marker(s) (AFP +/- DCP) at 2 months after treatment [2 months after treatment completion]

      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. Biological detection of tumoral marker(s) (AFP +/- DCP) at 4 months after treatment [4 months after treatment completion]

      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).

    5. Biological detection of tumoral marker(s) (AFP +/- DCP) at 6 months after treatment [6 months after treatment completion]

      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. MRI description of tumors at the hepatobiliary phase at baseline [at baseline]

      immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected

    7. MRI description of tumors at the hepatobiliary phase at 2 months after treatment [2 months after treatment completion]

      immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected

    8. MRI description of tumors at the hepatobiliary phase at 6 months after treatment [6 months after treatment completion]

      immunohistochemical markers and imaging features in hepatobiliary phase will be compared to see if any correlation can be detected

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hôpital de JOLIMONT Jolimont Hainaut Belgium 7100
    2 Centre Hospitalier Universitaire/CHC Saint Joseph Liege Liège Belgium 4000
    3 Cliniques Universitaires Saint Luc Brussels Woluwé Saint Lambert Belgium 1200
    4 Institut Jules Bordet/Hôpital Erasme Brussels Belgium 1000
    5 Clinique et Maternité Sainte Elisabeth/CHU Mont Godinne Namur Belgium 5000

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Xavier GEETS, Cliniques Universitaires Saint Luc/MIRO
    • Principal Investigator: Ivan BORBATH, Cliniques universitaires Saint-Luc

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Cliniques universitaires Saint-Luc- Université Catholique de Louvain
    ClinicalTrials.gov Identifier:
    NCT02958163
    Other Study ID Numbers:
    • 28248368
    First Posted:
    Nov 8, 2016
    Last Update Posted:
    Nov 7, 2017
    Last Verified:
    Mar 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain
    Hepatocellular cancer
    Stereotactic Body Radiotherapy
    Chemoembolization, Therapeutic
    Additional relevant MeSH terms:
    Liver Neoplasms
    Carcinoma, Hepatocellular
    Doxorubicin

    Study Results

    No Results Posted as of Nov 7, 2017