Nivolumab and Yttrium Y 90 Glass Microspheres in Treating Patients With Advanced Liver Cancer

NCT02837029 | Completed Phase 1 Results DMC

• 4 other identifiers: NU 16I01STU00203003P30CA060553NCI-2016-01001
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to identify maximum tolerated dose (MTD), that is, the highest dose of the study drug nivolumab that does not cause unacceptable side effects, for combination treatment of nivolumab and yttrium Y 90 glass microspheres (Y-90). Also, to evaluate the efficacy (the effect of drug on your tumor) and the tolerability (the effect of the drug on your body) of nivolumab, when given with standard of care Y-90 (Therasphere). Nivolumab is currently Food and Drug Administration (FDA) approved for other cancers, but has not yet been investigated in advanced or refractory hepatocellular carcinoma. Nivolumab is an antibody (a human protein that sticks to a part of the tumor and/or immune cells) designed to allow the body's immune system to work against tumor cells. Y-90 is currently FDA approved for the treatment of hepatocellular carcinomas, but has not yet been investigated in combination with nivolumab for this disease.

Conditions

Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  To identify maximum tolerated dose (MTD) of nivolumab for combination treatment of nivolumab following Y-90 in patients with advanced hepatocellular carcinoma. The MTD will be defined as the highest dose of nivolumab that causes dose limiting toxicities (DLTs) in \<2 of 6 patients. The Phase I portion of the study follows a 3+3 dose escalation design. Nivolumab has two dose levels: Level 1: 80mg IV every 2 weeks, Level 2: 240mg IV every 2 weeks. Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03. A DLT is defined as an Adverse Event (AE) or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤ 28 days (1 cycle) following the first dose of nivolumab and meets any of the criteria listed in the Protocol (Section 4.3.1).

  The first cycle of treatment with nivolumab (28 days)

• Phase IB: Objective Response Rate (ORR)

  Evaluate tumor response by assessing the proportion of patients with Objective response rate (ORR) (according to RECIST v. 1.1 criteria) to the combination treatment of nivolumab with Y-90 by examining imaging scans. Per RECIST v. 1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  At baseline and every 8 weeks for the first 13 months and then every 12 weeks up to 2 years

Secondary Outcomes (3)

• Number of Patients Who Experience Adverse Events

  During treatment where (1 Cycle = 28 days) the range of cycles attempted was 1-14 and up to 100 days following the last administration of study drug

• Progression Free Survival (PFS) at 24 Weeks (6 Months)

  Up to 24 weeks (6 months)

• Disease Control Rate (DCR)

  At 24 weeks (6 months)

Other Outcomes (3)

• PD-L1 Protein Expression

  At baseline

• Expression Level of Biomarker of Inflammatory/Immune Signature

  Up to 2 years

• Circulating Free DNA (cfDNA) Mutation Analyses

  Every 8 weeks for the first 24 weeks then every 16 weeks up to 2 years

Study Arms (1)

Treatment (yttrium Y 90 glass microspheres, nivolumab)

EXPERIMENTAL

Patients receive yttrium Y 90 glass microspheres IA. Approximately 4 weeks after yttrium Y 90 glass microspheres treatment, patients receive nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Radiation: Yttrium Y 90 Glass Microspheres

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (yttrium Y 90 glass microspheres, nivolumab)

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 IA

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)
• NOTE: If the patient does not have histological confirmation of disease by biopsy, diagnosis of HCC must be documented with approval by a tumor board or other multidisciplinary conference
• Patients must have at least 1 lesion that is measurable using RECIST guidelines.
• NOTE: A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per RECIST, and has clearly progressed.
• NOTE: For patients with infiltrative disease, evaluable disease needs to be confirmed by pathology if RECIST measurements cannot be made.
• Patients must have advanced disease that is not amenable to transplant or resection
• Patients may be treatment naive or have received any number of prior therapies
• NOTE: Prior immunotherapy is contraindicated and not permitted
• 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 envelope 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 if controlled with medication, in the opinion of the investigator
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Patients must have adequate organ function within 14 days prior to registration as determined by:
• Hematological (without growth factor support)
• Hemoglobin \>= 8.5 g/dL (without the use of growth factors)
• Absolute neutrophil count (ANC) \>= 1000

You may not qualify if:

• Patients must not have had prior treatment with nivolumab or any other PDL1 or PD-1 antagonists
• Patients must not have a history of severe allergic reactions (i.e., grade 4 allergy, anaphylactic reaction from which the subject did not recover within 6 hours of institution of supportive care) to any unknown allergens or any components of the nivolumab formulations
• Patients diagnosed or treated for malignancy other than HCC are not eligible unless they meet one of the following exceptions:
• Malignancy treated with curative intent and with no known active disease present for \>= 3 years before registration and felt to be at low risk for recurrence by the treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease
• 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
• Guillain-Barre syndrome
• Myasthenia gravis
• Systemic autoimmune disease such as systemic lupus erythematosus (SLE)
• Connective tissue diseases
• Scleroderma

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

Limitations and Caveats

The total accrual goal of 40 patients was not met. Due to funding issues, Phase 1b of the study never opened to accrual.

Results Point of Contact

• Title: Aparna Kalyan, MBBS, FRACP
• Organization: Northwestern University, Feinberg School of Medicine

Aparna.kalyan@northwestern.edu

312 926 4291

Study Officials

• Aparna Kalyan, MBBS, FRACP

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: July 15, 2016
• First Posted: July 19, 2016
• Study Start: July 1, 2016
• Primary Completion: July 17, 2019
• Study Completion: November 1, 2020
• Last Updated: January 25, 2022
• Results First Posted: August 11, 2020

Record last verified: 2022-01

Locations

US (1)