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A Study to Test the Safety and Feasibility of Nivolumab With Drug Eluting Bead Transarterial Chemoembolization in Patients With Liver Cancer

NCT03143270

Description:

The purpose of the study is to find out the effects of using nivolumab with Drug Eluting Bead Transarterial Chemoembolization (deb-TACE) in the treatment of liver cancer.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Test the Safety and Feasibility of Nivolumab With Drug Eluting Bead Transarterial Chemoembolization in Patients With Liver Cancer
  • Official Title: A Multicenter Pilot Study of Nivolumab With Drug Eluting Bead Transarterial Chemoembolization in Patients With Advanced Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 17-087
  • NCT ID: NCT03143270

Conditions

  • Liver Cancer

Interventions

DrugSynonymsArms
Drug Eluting Bead Transarterial Chemoembolizationdeb-TACECohort 1, deb-TACE + Nivolumab
NivolumabCohort 1, deb-TACE + Nivolumab

Purpose

The purpose of the study is to find out the effects of using nivolumab with Drug Eluting Bead Transarterial Chemoembolization (deb-TACE) in the treatment of liver cancer.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1, deb-TACE + NivolumabExperimental3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Two weeks after deb-TACE, participants will begin nivolumab every two weeks for up to one year. If no participants experience a dose limiting toxicity (DLT), or 1 of 6 participants experiences a DLT, a new group of participants will be enrolled into Cohort 2.
  • Drug Eluting Bead Transarterial Chemoembolization
  • Nivolumab
Cohort 2, deb-TACE + NivolumabExperimental3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Participants will receive nivolumab every two weeks for up to one year, starting 4 weeks prior to deb-TACE (week -4). Participants in this cohort will not receive nivolumab on the day of deb-TACE. If no participants experience a DLT in the initial group of 3 participants or if 1 of 6 participants experiences a DLT, a new group of participants will be enrolled into Cohort 3.
  • Drug Eluting Bead Transarterial Chemoembolization
  • Nivolumab
Cohort 3, deb-TACE + NivolumabExperimental3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Nivolumab will be dosed every two weeks starting 4 weeks prior to deb-TACE (Week 4) and continue every 2 weeks for up to one year. If no participants experience a DLT in the initial group of 3 participants, an additional 3 participants will be added to confirm safety. If less than or equal to 1 of 6 participants experiences a DLT, this will be considered the optimal schedule.
  • Drug Eluting Bead Transarterial Chemoembolization
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Age 18 and over at the time of consent

          -  Histology and/or cytology confirmed HCC per the enrolling institution

          -  Measurable disease per RECIST v1.1

          -  Disease not amenable to curative or transplant surgery (BCLC Stage B); disease must be
             reviewed by members of disease management team at the local enrolling institution and
             be amenable to deb-TACE to treat all sites of disease in one session

          -  ECOG Performance status 0 or 1

          -  Child-Pugh Class A

          -  Adequate bone marrow, hepatic, and renal function defined as:

               -  Platelet count ≥ 75,000/mm3

               -  Absolute neutrophil count ≥ 1,000/mm3

               -  Hemoglobin ≥ 9 g/dL

               -  Total bilirubin < 3.0 × ULN (upper limit of normal)

               -  Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 5 × ULN

               -  Albumin ≥ 2.8 g/dL

               -  Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 40 mL/min as
                  determined by the Cockcroft-Gault equation

          -  Suppression of HBV (≤ 100 IU/mL by HBV PCR) with antivirals per the local standard of
             care if prior or current HBV exposure or infection.

          -  Active HCV infection without treatment is permitted. Concomitant treatment of HCV is
             not permitted on this study.

        Exclusion Criteria:

          -  Vascular invasion or extrahepatic spread

          -  History of liver allograft; prior hepatic resection is allowed.

          -  Prior embolization and/or ablation

          -  Contraindication to angiography/embolization procedure based on judgment of the
             treating investigator.

          -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or
             any other antibody or drug specifically targeting T-cell costimulation or immune
             checkpoint pathways

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS)

          -  A history of a severe contrast allergy (.i.e. anaphylaxis) not controlled with
             premedication

          -  Patients should be excluded if they have a condition requiring chronic systemic
             treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other
             immunosuppressive medications within 14 days of study drug administration. Inhaled or
             topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents
             are permitted in the absence of active autoimmune disease. Patients with contrast
             allergies who can tolerate contrast with corticosteroid premedication are not
             excluded.

          -  An active, known or suspected autoimmune disease. Subjects are permitted to enroll if
             they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to
             autoimmune condition only requiring hormone replacement, psoriasis not requiring
             systemic treatment, or conditions not expected to recur in the absence of an external
             trigger.

          -  Subjects with history of another primary cancer, with the exception of: a) curatively
             resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ;
             or c) other primary solid tumor with no known active disease present that in the
             opinion of the investigator will not affect patient outcome in the setting of current
             HCC diagnosis.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of the investigational product or interpretation of subject safety or study
             results

          -  Women of childbearing potential (WOCBP) or sexually active men must use appropriate
             method(s) of contraception.

               -  Women of childbearing potential (WOCBP) must use appropriate method(s) of
                  contraception while on study treatment. WOCBP should use an adequate method to
                  avoid pregnancy during study treatment and for 5 months (30 days plus the time
                  required for nivolumab to undergo five half-lives) after the last dose of
                  investigational drug

               -  Men who are sexually active with WOCBP must use any contraceptive method with a
                  failure rate of less than 1% per year Men receiving nivolumab and who are
                  sexually active with WOCBP will be instructed to adhere to contraception during
                  study treatment and for a period of 7 months after the last dose of
                  investigational product

               -  Women who are not of childbearing potential (ie, who are postmenopausal or
                  surgically sterile, as well as azoospermic men do not require contraception

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the
             start of nivolumab. Elevated HCG for other explained and documented reasons is
             allowed.

          -  Lactating woman
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:12 months
Safety Issue:
Description:The percentage of subjects who experience toxicity at each schedule will be calculated. Frequencies of toxicities will be tabulated according to the NCI CTCAE scale (version 4.03).

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • nivolumab
  • deb-TACE
  • 17-087

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