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Transarterial Chemoembolization Compared With Stereotactic Body Radiation Therapy or Stereotactic Ablative Radiation Therapy in Treating Patients With Residual or Recurrent Liver Cancer Undergone Initial Transarterial Chemoembolization

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ClinicalTrials.gov Identifier: NCT02762266
Recruitment Status : Recruiting
First Posted : May 4, 2016
Last Update Posted : January 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Stanford University

Brief Summary:
This randomized phase III trial studies how well transarterial chemoembolization (TACE) works compared to stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR) in patients with liver cancer that remain after attempts to remove the cancer have been made (residual) or has come back (recurrent). TACE is a minimally invasive, image-guided treatment procedure that uses a catheter to deliver both chemotherapy medication and embolization materials into the blood vessels that lead to the tumors. SBRT or SABR may be able to send radiation directly to the tumor and cause less damage to normal liver tissue. It is not yet known whether TACE is more effective than SBRT or SABR in treating patients with persistent or recurrent liver cancer who have undergone initial TACE.

Condition or disease Intervention/treatment Phase
Child-Pugh Class A Child-Pugh Class B Recurrent Hepatocellular Carcinoma Radiation: Stereotactic Body Radiation Therapy Procedure: Transarterial Chemoembolization Drug: embolic agent Drug: lipiodol Phase 3

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the freedom from local progression (FFLP) of TACE versus (vs) SABR in patients with persistent hepatocellular carcinoma (HCC) after TACE.

SECONDARY OBJECTIVES:

I. To determine the progression-free survival (PFS) of TACE vs SABR in patients with persistent HCC after initial TACE.

II. To determine the overall survival (OS) of TACE vs SABR for persistent HCC. III. To determine the toxicities associated with TACE or SABR for persistent HCC.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo TACE.

ARM II: Beginning within 2 weeks of the radiation set-up scan and within 4 weeks of fiducial seed implantation (if applicable), patients undergo image guided SBRT 3 fractions within 1 week or 5 fractions within 2 weeks.

After completion of study treatment, patients are followed up for 1-2 weeks, 1, 3, 6, 12, and 18 months, and every 6 months up to 3 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: International Randomized Study of Transarterial Chemoembolization (TACE) Versus Stereotactic Body Radiotherapy (SBRT) / Stereotactic Ablative Radiotherapy (SABR) for Residual or Recurrent Hepatocellular Carcinoma After Initial TACE
Actual Study Start Date : February 27, 2016
Estimated Primary Completion Date : February 27, 2019
Estimated Study Completion Date : February 27, 2021

Arm Intervention/treatment
Active Comparator: Arm I (TACE)
Patients undergo TACE.
Procedure: Transarterial Chemoembolization
Undergo TACE
Other Name: TACE

Drug: embolic agent

. Acceptable embolic agents include:

  • Gelatin sponge (gelfoam)
  • Polyvinyl alcohol (PVA) particles
  • Microspheres / Embolic beads

Drug: lipiodol
Experimental: Arm II (SBRT)
Beginning within 2 weeks of the radiation set-up scan and within 4 weeks of fiducial seed implantation (if applicable), patients undergo image guided SBRT 3 fractions within 1 week or 5 fractions within 2 weeks.
Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Name: SBRT




Primary Outcome Measures :
  1. Median FFLP [ Time Frame: Up to 12 months ]
    The time to freedom from local progression will be estimated by competing risk models with death and regional or distant progression as competing risks. Risk factors such as tumor size and institution will be tested in a multivariate Cox regression model adjusting for the competing risks.


Secondary Outcome Measures :
  1. Comparison of median freedom from extra hepatic progression [ Time Frame: Up to 16 weeks ]
    The time to freedom from extra hepatic progression will be estimated by competing risk models with death as a competing risk. Risk factors such as tumor size and institution will be tested in a multivariate Cox regression model adjusting for the competing risks.

  2. Median extra hepatic PFS for patients with tumors smaller than 3 cm and greater than 3 cm per treatment group [ Time Frame: At 18 months ]
    Extra hepatic PFS within each subgroup will be summarized by cumulative incidence function estimators adjusted for the competing risk of death or regional or distant progression.

  3. Median FFLP for patients with tumors smaller than 3 cm and with tumors greater than 3 cm per treatment group [ Time Frame: At 18 months ]
    FFLP within each subgroup will be summarized by cumulative incidence function estimators adjusted for the competing risk of death or regional or distant progression.

  4. Median OS [ Time Frame: Time from randomization until death from any cause, assessed up to 3 years ]
    Overall survival will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula. Log rank tests will be used to compare treatment groups. Cox proportional hazard models will be used to estimate hazard ratios between treatment groups and to assess other risk factors, in particular the effect of tumor size and the impact of the different institutions.

  5. Median OS for patients with tumors smaller than 3 cm and greater than 3 cm per treatment group [ Time Frame: At 18 months ]
    Within each subgroup OS will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula.

  6. Median PFS [ Time Frame: Time from randomization until death or any progression including local, regional or distant progression, assessed up to 3 years ]
    Progression free survival will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula. Log rank tests will be used to compare treatment groups. Cox proportional hazard models will be used to estimate hazard ratios between treatment groups and to assess other risk factors, in particular the effect of tumor size and the impact of the different institutions.

  7. Median PFS for patients with tumors smaller than 3 cm and greater than 3 cm per treatment group [ Time Frame: At 18 months ]
    Within each subgroup PFS will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula.

  8. Serum Alpha-Fetoprotein level (AFP) [ Time Frame: Up to 18 months ]
    The impact of elevated AFP level on time to event endpoints: FFLP, PFS, extra hepatic PFS and OS will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed hepatocellular carcinoma (HCC) by one of the following:

    • Histopathology
    • One radiographic technique that confirms a lesion >= 1 cm with arterial hypervascularization with washout on delayed phase
  • Radiographic evidence of persistent, progressive, or recurrent disease in an area previously treated with TACE and determined from 3 months after initial TACE; this evaluation should be within 6 weeks of date of study eligibility
  • Unifocal liver tumors not to exceed 7.5 cm in greatest axial dimension; multifocal lesions will be restricted to lesions that can be treated within a single target volume within the same liver segment and to an aggregate of 10 cm as long as the dose constraints to normal tissue can be met
  • Eastern Clinical Oncology Group (ECOG) performance status 0, 1 or 2
  • Patients with liver disease classified as Child Pugh class A or B, with score =< 9
  • Life expectancy >= 6 months
  • Albumin >= 2.4 g/dL
  • Total bilirubin =< 3 mg/dL
  • International normalized ratio (INR) =< 1.5
  • Creatinine =< 2.0 mg/dL
  • Ability of the research subject or authorized legal representative to understand and have the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior radiotherapy to the upper abdomen
  • Prior radioembolization to the liver
  • Prior radiofrequency ablation (RFA) to index lesion
  • Liver transplant
  • Active gastrointestinal bleed within 2 weeks of study enrollment
  • Ascites refractory to medical therapy (mild to moderate ascites is allowed)
  • Women who are pregnant or breastfeeding
  • Administration of chemotherapy within the last 1 month
  • Extrahepatic metastases
  • Participation in another concurrent treatment protocol
  • Prior history of malignancy other than HCC, dermatologic basal cell or squamous cell carcinoma

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02762266


Contacts
Contact: Samantha Wong 650-498-8495 swong8@stanford.edu

Locations
United States, California
Stanford University, School of Medicine Recruiting
Palo Alto, California, United States, 94304
Contact: Rachel Freiberg    650-725-0438    rachelf@stanford.edu   
Principal Investigator: Daniel T. Chang         
Japan
Hokkaido University Hospital Not yet recruiting
Sapporo, Hokkaido, Japan, 060-8648
Contact: Rei Kikuchi    81-11-706-7600    reik777@huhp.hokudai.ac.jp   
Principal Investigator: Hiroki Shirato         
Sponsors and Collaborators
Stanford University
National Cancer Institute (NCI)
Investigators
Principal Investigator: Daniel Chang Stanford University

Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT02762266     History of Changes
Other Study ID Numbers: IRB-35937
NCI-2016-00418 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA124435 ( U.S. NIH Grant/Contract )
HEP0052 ( Other Identifier: OnCore ID )
First Posted: May 4, 2016    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Ethiodized Oil
Antineoplastic Agents