Nivolumab and Yttrium-90 in Treating Patients With Liver Cancer Undergoing Surgical Resection

NCT03812562 | Terminated Early Phase 1 DMC FDA Drug

• 3 other identifiers: NU 18I03NCI-2018-03602P30CA060553
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase I trial studies how well nivolumab and yttrium-90 work in treating patients with liver cancer who are undergoing surgical resection. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radioactive drugs, such as yttrium-90, may carry radiation directly to tumor cells and not harm normal cells. Giving nivolumab and yttrium-90 may work better in treating patients with liver cancer.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Recurrence rate

  This primary dichotomous endpoint will be summarized at each time point using a table of frequencies and counts.

  Up to 3 years post-treatment

Secondary Outcomes (3)

• Incidence of adverse events

  Up to 30 days post-treatment

• Overall survival (OS)

  Up to 5 years post-treatment

• Overall increase in future liver remnant (FLR)

  Up to 3 years post-treatment

Study Arms (1)

Treatment (yttrium Y 90 glass microspheres, nivolumab)

EXPERIMENTAL

Patients receive standard of care yttrium Y 90 glass microspheres IV. Within 1-2 weeks of completing of yttrium-90 treatment, patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity. If imaging shows adequate FLR and at least stable disease, patients will undergo resection within 2 weeks after the last dose of nivolumab. Patients who do not complete resection due to feasibility and have progressed or have evidence of high-risk explant may continue to receive nivolumab IV every 2 weeks for up to 1 year.

Biological: Nivolumab; Radiation: Yttrium Y 90 Glass Microspheres

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (yttrium Y 90 glass microspheres, nivolumab)

Yttrium Y 90 Glass Microspheres RADIATION

Given IV

Also known as: TheraSphere

Treatment (yttrium Y 90 glass microspheres, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a diagnosis of hepatocellular carcinoma (HCC) confirmed by American Association for Study of Liver Diseases (AASLD) guidelines with a Childs-Pugh score of A or B (but, =\< Childs score B8)
• Patients must be eligible for resection based on preserved hepatic function and lack of clinically significant portal hypertension (HTN)
• NOTE: Patients with branch or lobar portal vein thrombosis (PVT) who are otherwise a candidate for resection will be included
• Patients must have a pre-established need for Y90 therapy prior to resection for FLR growth and/or retraction of tumor away from major vessel to improve margins
• Patients must have measurable disease according to the standard Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Patients with chronic hepatitis B are eligible as long as they have evidence of ongoing viral replication (detectable hepatitis B surface antigen \[HBsAg\], hepatitis B e-antigen \[HBeAg\], or hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\]). They must have HBV DNA viral load \< 100 IU/mL at screening. In addition, they must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy. If not on antiviral therapy at screening, then the subject must initiate treatment per regional standard of care guidelines at the time of consent. Both HBeAg positive and negative patients will be included
• Patients positive for hepatitis C are permitted at physician discretion
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate organ and bone marrow functions:
• Leukocytes \>= 2,000/mcL
• Absolute neutrophil count \>= 1,500/uL
• Hemoglobin \>= 9 g/dL; transfusion is permitted for eligibility, but should be \>= 7 days from registration
• Platelets \>= 50,000/mcL
• Total bilirubin =\< 2.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy =\< 28 days prior to registration are not eligible
• Patients who have had prior immunotherapy including interleukin-2 and immune checkpoint antagonist and/or agonists are not eligible
• Patients who have not recovered to their baseline, =\< grade 1, or tolerable grade 2 (as documented by the treating physician) from adverse events due to agents administered \>= 28 days earlier are not eligible
• Patients who have received any other investigational agents =\< 28 days prior to registration are not eligible
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or Y90 are not eligible
• Patients who have had prior treatment with an anti-PD1, anti-PD-L1, antiPD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways are not eligible
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded. These include but are not limited to patients with a history of:
• Immune related neurologic disease
• Multiple sclerosis
• Autoimmune (demyelinating) neuropathy
• Pure red cell aplasia
• Guillain-Barre syndrome
• Myasthenia gravis
• Systemic autoimmune disease such as systemic lupus erythematosus (SLE)
• Connective tissue diseases

Sponsors & Collaborators

• Northwestern University: lead
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Laura Kulik, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2019
• First Posted: January 23, 2019
• Study Start: February 7, 2019
• Primary Completion: October 19, 2023
• Study Completion: October 19, 2023
• Last Updated: February 21, 2024

Record last verified: 2024-02

Locations

US (1)