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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

          -  Child-Pugh Scoring Note: PI INR <1.7 is not required for patients on anticoagulation
             agents. Patients who are being therapeutically anticoagulated with an agent such as
             Coumadin or heparin will be allowed to participate provided that no prior evidence of
             underlying abnormality in these parameters exists

          -  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 is allowed as long as the patient has progressed
             with a new RECIST measurable lesion

          -  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

Last Updated

December 21, 2020