search
Back to results

Transarterial Chemoembolization (TACE) With or Without Stereotactic Body Radiotherapy (SBRT) in Hepatocellular Carinoma (TACERT)

Primary Purpose

Hepatocellular Carcinoma

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
transarterial chemoembolization
TACE plus RT
Sponsored by
Lawson Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 95 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • HCC (diagnosed through biopsy or radiological criteria)
  • Age >18 years of age
  • Number of lesions: not more than 3 lesions
  • Lesion size: up to 10 cm (and up to 10 cm cumulative diameter)
  • Unilobar +/- segment 4
  • Child-Pugh A within 6 weeks prior to study entry
  • Barcelona Clinic (BCLC) Stage A/B
  • Absence of comorbidities
  • ECOG Performance Status 0-2
  • Must be fit (eligible) for RT and TACE
  • Unsuitable/unwilling for resection or transplant or radiofrequency ablation (RFA) or if these options are not available
  • All blood work obtained within 6 weeks prior to study entry with adequate organ marrow 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 < 1.7 (unless on Coumadin/Warfarin) Albumin ≥ 28 g/L AST and ALT < 5 times ULN Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min

  • May have had previous surgery, ethanol injection and RFA to the liver
  • No evidence of metastatic disease including nodal or distant metastases (clinically defined by each institution).
  • Distance between GTV (lesion) and luminal structures (including esophagus, stomach, duodenum, small or large bowel) is >5 mm

Exclusion Criteria:

  • 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.
  • Major vascular invasion/thrombus
  • Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) Raoul et al (2011)
  • Previous TACE and radiation to the liver (including SIRT )
  • Life-threatening condition including untreated HIV and active hepatitis B/C
  • Pregnancy or women of childbearing potential require a negative pregnancy test within 28 days

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    TACE alone

    TACE plus RT

    Arm Description

    Transarterial chemoembolization (TACE)

    Combination of transarterial chemoembolization and radiation (TACERT)

    Outcomes

    Primary Outcome Measures

    Intrahepatic progression
    Lesion growth as characterized by RECIST criteria

    Secondary Outcome Measures

    Response rate - Modified RECIST criteria
    Response of treated lesions using modified RECIST criteria
    Local failure - within 1 cm from the original tumor volume
    evidence of disease within 1cm of the tumor
    Overall survival
    overall survival percentage
    Toxicity
    Measured by NCI - CTC V4.0 at year 2
    QoL-quality of life
    EORTC QLQC30 at year 2

    Full Information

    First Posted
    March 11, 2016
    Last Updated
    February 20, 2020
    Sponsor
    Lawson Health Research Institute
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03079778
    Brief Title
    Transarterial Chemoembolization (TACE) With or Without Stereotactic Body Radiotherapy (SBRT) in Hepatocellular Carinoma
    Acronym
    TACERT
    Official Title
    Transarterial Chemoembolization (TACE) With or Without Stereotactic Body Radiotherapy (SBRT) in Hepatocellular Carinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2019
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Opened up a separate Clinicaltrials.gov trial form, study ID TACE
    Study Start Date
    July 31, 2019 (Anticipated)
    Primary Completion Date
    August 2022 (Anticipated)
    Study Completion Date
    August 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Lawson Health Research Institute

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Hypothesis: Patients with hepatocellular carcinoma (HCC) have few options if they fail or are unable to undertake surgery, transarterial chemoembolization (TACE) and/or chemotherapy. Radiation (RT) in a range of doses has been combined with TACE in several case cohort studies demonstrating safety and a dramatic improvement in survival. Clearly these trials are subject to bias due to non-randomized selection, possible lack of generalizability to Canadian patients, and heterogeneous patient populations. Objective: Therefore, there is a high priority need to investigate the addition of RT to TACE in a randomized fashion to determine if we can improve survival in this rapidly growing poor prognosis patient population that have no other options. Methodology: TACE eligible patients with HCC will be randomized to TACE alone or TACE plus radiation (TACERT). They cannot be eligible for standard treatments such as transplant and resection. Primary endpoint will be time-to-intrahepatic-progression. Secondary endpoints will be response rate (Modified RECIST criteria), overall survival, local failure, extrahepatic failure, toxicity, quality of life and economic feasibility.
    Detailed Description
    DETAILED OUTLINE OF RESEARCH PROPOSAL Current State of Knowledge Primary liver cancer, hepatocellular carcinoma (HCC), is a major health problem worldwide. It is the 5th most common cancer and the 3rd most common cause of cancer death in the world. Eighty-five percent of cases occur in developing countries, while in the United States and Canada, it is the fastest growing cancer. General Treatment Overview: HCC tends to remain within the liver and, therefore, cure with preserved liver function is possible. Surgical resection results in 5-year survival rates of 60%-70%. Liver transplantation can cure both the cancer and underlying liver disease. Four-year survival for HCC within the Milan criteria (single HCC <5 cm or ≤3 HCC <3 cm) is 70%-85% after transplantation. Unfortunately, most patients are not resectable. Transarterial chemoembolization (TACE) has become the mainstay of treatment for unresectable HCC. What makes TACE relatively safe is the liver-unique vascular supply from the portal vein, whereas HCC is supplied almost entirely by branches of the hepatic artery. In a randomized controlled trial for unresectable HCC not suitable for a curative intent, transarterial chemoembolisation or TACE were compared to conservative treatment. TACE induced objective responses (complete and partial response) that were sustained for at least 6 months in 35% of cases. Survival probabilities at 1 year and 2 years were 82% and 63% for TACE, significantly better than 63% and 27% obtained with conservative treatment. Overall survival at 1 and 2 years was also significantly better for the chemoembolization group 57% and 31% vs. 32% and 11%. However, many patients have large tumours and response rates decline rapidly with increasing size. TACE alone results in 2 year overall survivals of 42%, 0 and 0 for lesions 5-7cm, 8-10cm, and >10cm, respectively. Therefore, additional locally ablative treatments are being sought. In the same report, TACE plus radiation results in 2 year overall survivals of 63%, 50% and 17% for lesions 5-7cm, 8-10cm, and >10cm, respectively. External beam radiotherapy has long been considered to have a very limited role in the treatment of liver tumors. This is due to the fact that the minimum dose required for local ablation exceeded the dose that would result in liver toxicity. The technical development of stereotactic body radiation therapy (SBRT), alone or in combination with TACE, renewed interest in radiation for HCC. This work was done mainly by two groups, in Michigan and Stockholm, who demonstrated that the delivery of high doses of radiation to limited volumes of the liver had promising results in terms of local control and survival with acceptable toxicity. Dr. Lock and his team are one of the first centres to initiate this type of work and currently have one of the largest databases outside of asia. In addition, he leads one of only two groups in Canada able to dose escalate based on radiobiological parameters thereby providing the highest possible doses within known toxicity constraints. For SBRT, advanced techniques are used to very accurately deliver a high total dose to the target in a small number of daily fractions while avoiding dose delivery to surrounding healthy structures. SBRT is offered as an ablative radical local treatment. In total, eleven primary series reported on tumor response and survival of around 300 patients who have been treated with stereotactic body radiation therapy as primary therapy for HCC. The reported percentage of objective responses defined as complete and partial was ≥64% in 7 of 8 series. Median survival between 11.7 and 32 months has been observed. Toxicity, based on multiple case series trials, indicate that the treatment is considered safe. The most common CTC grade 3-4 toxicity was elevation of liver enzymes. For unresectable cases, both TACE and SBRT have been used safely and with good efficacy as separate treatments. Particularly for larger lesions that are more commonly seen in London, the outcome remains suboptimal compared to surgery. Combined treatment case series have shown dramatic results, but there has not been any randomized trial to compare the value of combining the two modalities. Therefore a clinical study comparing SBRT and SBRT+TACE will be significant as it addresses a common problem in one of the two most deadly cancers. Combined Modality Treatment RT in a range of doses has been combined with TACE in several case cohort studies. One example is a phase 1 dose escalation study that demonstrated that 62 Gy and 52 Gy were safe doses for HCC <10 cm and >10 cm, respectively, in conjunction with TACE. Koo et al prospectively studied 42 patients who received TACE followed by RT. Survival in this cohort was improved compared with a historical control group of 29 patients who received TACE alone (median survival 11.7 vs. 4.7 months). Four studies specifically compared cohorts of patients that received TACE alone versus TACE+SBRT. All demonstrated significant improvement in response rates and overall survival. Clearly these trials are subject to bias due to non-randomized selection, possible lack of generalizability to Canadian patients, and heterogeneous patient populations. Therefore, there is an important clinical need to investigate combined RT+TACE to improve outcomes in this rapidly growing poor prognosis patient population that has few options. Research Design and Methodology The objective is to demonstrate superiority of SBRT in addition to TACE in terms of intrahepatic disease progression versus TACE alone using a randomized Phase III design. Phase I/II data has been published with recent data providing accurate event rates for statistical estimation of a small sample size requirement for this endpoint.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatocellular Carcinoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    randomized to radiation (RT) or TACE plus RT (TACERT)
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    TACE alone
    Arm Type
    Active Comparator
    Arm Description
    Transarterial chemoembolization (TACE)
    Arm Title
    TACE plus RT
    Arm Type
    Experimental
    Arm Description
    Combination of transarterial chemoembolization and radiation (TACERT)
    Intervention Type
    Procedure
    Intervention Name(s)
    transarterial chemoembolization
    Intervention Description
    Transcatheter arterial chemoembolization (also called transarterial chemoembolization or TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply
    Intervention Type
    Radiation
    Intervention Name(s)
    TACE plus RT
    Other Intervention Name(s)
    radiobiological guided radiation
    Intervention Description
    radiobiologically guided radiation
    Primary Outcome Measure Information:
    Title
    Intrahepatic progression
    Description
    Lesion growth as characterized by RECIST criteria
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    Response rate - Modified RECIST criteria
    Description
    Response of treated lesions using modified RECIST criteria
    Time Frame
    2 years
    Title
    Local failure - within 1 cm from the original tumor volume
    Description
    evidence of disease within 1cm of the tumor
    Time Frame
    2 years
    Title
    Overall survival
    Description
    overall survival percentage
    Time Frame
    2 years
    Title
    Toxicity
    Description
    Measured by NCI - CTC V4.0 at year 2
    Time Frame
    2 years
    Title
    QoL-quality of life
    Description
    EORTC QLQC30 at year 2
    Time Frame
    2 years
    Other Pre-specified Outcome Measures:
    Title
    Cost-benefit
    Description
    costs of performing both treatments versus TACE alone
    Time Frame
    2 years
    Title
    Extrahepatic failure
    Description
    enumeration of number of cancers outside the liver
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    95 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: HCC (diagnosed through biopsy or radiological criteria) Age >18 years of age Number of lesions: not more than 3 lesions Lesion size: up to 10 cm (and up to 10 cm cumulative diameter) Unilobar +/- segment 4 Child-Pugh A within 6 weeks prior to study entry Barcelona Clinic (BCLC) Stage A/B Absence of comorbidities ECOG Performance Status 0-2 Must be fit (eligible) for RT and TACE Unsuitable/unwilling for resection or transplant or radiofrequency ablation (RFA) or if these options are not available All blood work obtained within 6 weeks prior to study entry with adequate organ marrow 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 < 1.7 (unless on Coumadin/Warfarin) Albumin ≥ 28 g/L AST and ALT < 5 times ULN Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min May have had previous surgery, ethanol injection and RFA to the liver No evidence of metastatic disease including nodal or distant metastases (clinically defined by each institution). Distance between GTV (lesion) and luminal structures (including esophagus, stomach, duodenum, small or large bowel) is >5 mm Exclusion Criteria: 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. Major vascular invasion/thrombus Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) Raoul et al (2011) Previous TACE and radiation to the liver (including SIRT ) Life-threatening condition including untreated HIV and active hepatitis B/C Pregnancy or women of childbearing potential require a negative pregnancy test within 28 days
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Michael Lock, MD
    Organizational Affiliation
    University of Western Ontario, Canada
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Will be centrally registered data, freely shareable under contract as per ICMJE
    IPD Sharing Time Frame
    available January 2018
    IPD Sharing Access Criteria
    No access limitations
    Citations:
    PubMed Identifier
    25186290
    Citation
    Jacob R, Turley F, Redden DT, Saddekni S, Aal AK, Keene K, Yang E, Zarzour J, Bolus D, Smith JK, Gray S, White J, Eckhoff DE, DuBay DA. Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of >/= 3 cm. HPB (Oxford). 2015 Feb;17(2):140-9. doi: 10.1111/hpb.12331. Epub 2014 Sep 4.
    Results Reference
    background

    Learn more about this trial

    Transarterial Chemoembolization (TACE) With or Without Stereotactic Body Radiotherapy (SBRT) in Hepatocellular Carinoma

    We'll reach out to this number within 24 hrs