search
Back to results

Concurrent Nivolumab and External Beam Radiation Therapy for Patients With Advanced HCC (Nextrah)

Primary Purpose

Advanced Hepatocellular Carcinoma

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Nivolumab
Sponsored by
National Cancer Center, Korea
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Hepatocellular Carcinoma focused on measuring External Beam Radiation Therapy, Advanced Hepatocellular Carcinoma Who Have Vascular Invasion, Nivolumab

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Patients with HCC meeting all of following criteria;

    1. Signed written informed consent
    2. Age >= 20
    3. Histological or clinical diagnosis of HCC based on the guidelines of the Korean Liver Cancer Association-National Cancer Center17
    4. Having at least one typical enhanced measurable index lesion (in the liver) by dynamic CT or dynamic contrast-enhanced MRI

    5. Presence of major vascular invasion on dynamic CT or dynamic MRI

      ① an intraluminal filling defect adjacent to the primary tumor in portal vein, hepatic vein, and/or inferior vena cava

      ② an enhancement of the filling defect on arterial phase and a washout on portal/delayed phases.

    6. Sorafenib naïve or sorafenib experienced
    7. Child-Pugh class A
    8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
    9. Life expectancy of at least 16 weeks

    10. Adequate hematologic and hepatic function (should be obtained within 14 days prior to screening:

      • Hemoglobin ≥ 9.0 g/dL

        • Absolute neutrophil count (ANC) ≥ 1,000/mm3 ③ Platelet count ≥ 50,000/μL

          • Total bilirubin < 2.5 mg/dL

            • Serum albumin >2.8 g/dL ⑥ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × upper limit of normal (ULN) ⑦ Prothrombin time in INR ≤ 1.8 × ULN ⑧ Serum creatinine ≤ 1.5 mg/dL
    11. Women of childbearing potential and men must agree to use highly efficient contraception since signing of the IC form until at least 5 months (women) and 7 months (men) after the last study drug administration.

Exclusion Criteria:

  • Patients with HCC meeting all of following criteria;

    1. Receipt of 2 or more prior systemic therapies for advanced HCC. Additional prior systemic therapies used as adjuvant or local therapy are allowed.
    2. Any type of anticancer agent (including investigational) within 2 weeks before enrollment
    3. Having active brain metastasis or leptomeningeal metastasis
    4. Moderate to severe or intractable ascites
    5. A history or presence of hepatic encephalopathy
    6. Presence of active bacterial infection
    7. Untreated active chronic hepatitis B
    8. History of portal hypertension with bleeding within the past 6 months
    9. Prior liver transplant
    10. Uncontrolled severe medical comorbidity
    11. Other malignant disease (a history of treated malignancy -other than HCC- is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years)
    12. Current or past history of hypersensitivity to nivolumab

Sites / Locations

  • National Cancer Center, Korea

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

single

Arm Description

Nivolumab 3mg/kg IV is administered as 30-minute IV infusion every 2 weeks. Prescription dose to PTVs as according to the following schema: PTV1: 30 - 50 Gy /10 fx, 5Gy fraction dose, 5 days/week (The prescribed dose to PTV will be decided by physician depending on the dose-volume histogram (DVH) constraints of the normal tissues, such as liver, bowel, etc. The detail of DVH constraints of normal tissues are summarized in the following table) PTV2: 30 Gy /10 fx, 3Gy fraction dose, 5 days/week

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)
Progression-free survival (PFS) is defined as the time from the date of treatment initiation to the date of the first observation of progressive disease (PD) by independent radiologic review according to RECIST criteria (version 1.1) or death from any cause.

Secondary Outcome Measures

Full Information

First Posted
September 28, 2020
Last Updated
October 26, 2020
Sponsor
National Cancer Center, Korea
Collaborators
Samsung Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT04611165
Brief Title
Concurrent Nivolumab and External Beam Radiation Therapy for Patients With Advanced HCC
Acronym
Nextrah
Official Title
A Phase II Study of Concurrent Nivolumab and External Beam Radiation Therapy for Patients With Advanced Hepatocellular Carcinoma Who Have Vascular Invasion With or Without Sorafenib-Experience in an HBV-endemic Area
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 15, 2019 (Actual)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Center, Korea
Collaborators
Samsung Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To investigate the efficacy and safety of nivolumab for patients with advanced HCC undergoing EBRT
Detailed Description
<Treatment phase> Nivolumab 3mg/kg IV is administered as 30-minute IV infusion every 2 weeks. External beam radiotherapy begins 2-7 days after the first dose of nivolumab. The study drug is continued until disease progression, unacceptable toxicity, withdrawal of consent or study closure. <Follow-Up phase > After the treatment phase, subjects will undergo follow up for survival every 12 weeks (± 7 days) from the last dose or the use of other anticancer treatments and/or therapies, and the survival follow up will be performed for at least 18 months after the enrollment of the last subject. The patient will be followed for survival follow up and the use of other anticancer treatments and/or therapies. Based on the assumed dropout rate of 12%, a total of 50 subjects need to perform the study (50=44/(1-0.12))

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Hepatocellular Carcinoma
Keywords
External Beam Radiation Therapy, Advanced Hepatocellular Carcinoma Who Have Vascular Invasion, Nivolumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
single
Arm Type
Experimental
Arm Description
Nivolumab 3mg/kg IV is administered as 30-minute IV infusion every 2 weeks. Prescription dose to PTVs as according to the following schema: PTV1: 30 - 50 Gy /10 fx, 5Gy fraction dose, 5 days/week (The prescribed dose to PTV will be decided by physician depending on the dose-volume histogram (DVH) constraints of the normal tissues, such as liver, bowel, etc. The detail of DVH constraints of normal tissues are summarized in the following table) PTV2: 30 Gy /10 fx, 3Gy fraction dose, 5 days/week
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
EBRT
Intervention Description
Nivolumab 3mg/kg IV is administered as 30-minute IV infusion every 2 weeks. EBRT begins 2-7 days after the first dose of nivolumab. The follow-up phase begins when the decision to discontinue study is made. The follow-up phase is defined as the day after the end of study treatment until the day the subject dies.
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
Progression-free survival (PFS) is defined as the time from the date of treatment initiation to the date of the first observation of progressive disease (PD) by independent radiologic review according to RECIST criteria (version 1.1) or death from any cause.
Time Frame
through study completion, an average of 2.5 year.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Patients with HCC meeting all of following criteria; Signed written informed consent Age >= 20 Histological or clinical diagnosis of HCC based on the guidelines of the Korean Liver Cancer Association-National Cancer Center17 Having at least one typical enhanced measurable index lesion (in the liver) by dynamic CT or dynamic contrast-enhanced MRI Presence of major vascular invasion on dynamic CT or dynamic MRI ① an intraluminal filling defect adjacent to the primary tumor in portal vein, hepatic vein, and/or inferior vena cava ② an enhancement of the filling defect on arterial phase and a washout on portal/delayed phases. Sorafenib naïve or sorafenib experienced Child-Pugh class A Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 Life expectancy of at least 16 weeks Adequate hematologic and hepatic function (should be obtained within 14 days prior to screening: Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count (ANC) ≥ 1,000/mm3 ③ Platelet count ≥ 50,000/μL Total bilirubin < 2.5 mg/dL Serum albumin >2.8 g/dL ⑥ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × upper limit of normal (ULN) ⑦ Prothrombin time in INR ≤ 1.8 × ULN ⑧ Serum creatinine ≤ 1.5 mg/dL Women of childbearing potential and men must agree to use highly efficient contraception since signing of the IC form until at least 5 months (women) and 7 months (men) after the last study drug administration. Exclusion Criteria: Patients with HCC meeting all of following criteria; Receipt of 2 or more prior systemic therapies for advanced HCC. Additional prior systemic therapies used as adjuvant or local therapy are allowed. Any type of anticancer agent (including investigational) within 2 weeks before enrollment Having active brain metastasis or leptomeningeal metastasis Moderate to severe or intractable ascites A history or presence of hepatic encephalopathy Presence of active bacterial infection Untreated active chronic hepatitis B History of portal hypertension with bleeding within the past 6 months Prior liver transplant Uncontrolled severe medical comorbidity Other malignant disease (a history of treated malignancy -other than HCC- is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years) Current or past history of hypersensitivity to nivolumab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joong Won Park
Organizational Affiliation
National Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Center, Korea
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

Concurrent Nivolumab and External Beam Radiation Therapy for Patients With Advanced HCC

We'll reach out to this number within 24 hrs