Nivolumab and Yttrium Y 90 Glass Microspheres in Treating Patients With Advanced Liver Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02837029|
Recruitment Status : Recruiting
First Posted : July 19, 2016
Last Update Posted : May 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Stage IIIA Hepatocellular Carcinoma Stage IIIB Hepatocellular Carcinoma Stage IIIC Hepatocellular Carcinoma Stage IVA Hepatocellular Carcinoma Stage IVB Hepatocellular Carcinoma||Other: Laboratory Biomarker Analysis Biological: Nivolumab Radiation: Yttrium Y 90 Glass Microspheres||Phase 1|
I. To identify MTD of nivolumab for combination treatment of nivolumab and Y-90 in this population.
I. To evaluate the proportion of patients with objective response rate (ORR) (according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria) to the combination treatment of nivolumab with Y-90.
II. To evaluate the proportion of patients alive and progression free at 24 weeks in the described population.
III. To evaluate the toxicities (according to the National Comprehensive Cancer Network [NCCN] Common Terminology Criteria for Adverse Events [CTCAE] version (v)4.03) and tolerability of nivolumab and Y-90 in patients with advanced hepatocellular carcinoma IV. To determine the disease control rate (DCR) to the combination of nivolumab and Y-90 at 24 months from the start of nivolumab treatment.
I. Programmed cell death 1 ligand 1 (PD-L1) protein on tumor cells and the expression levels of other markers of inflammatory/immune signature that may include but not be limited to programmed cell death protein 1 (PD-1), tumor necrosis factor receptor superfamily, member 4 (OX40), cluster of differentiation (CD) 73, CD39, T cell immunoglobulin and T-cell immunoglobulin and mucin-domain containing-3 (TIM3), glucocorticoid-induced tumour necrosis factor receptor (GITRL), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD3, CD4, CD8, CD45RO, forkhead box P3 (FOXP3), and granzyme by immunohistochemistry (IHC) and/or flow cytometry will be evaluated.
II. Whole exome sequencing and computational analyses will be performed to assess mutanome and immunome (subpopulations of immune cells).
III. Change in clonal burden landscape of various mutanome and immunome will be analyzed to investigate its correlation with treatment response or development of resistance to treatment.
OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase Ib study.
Patients receive yttrium Y 90 glass microspheres intraarterially (IA). Approximately 7-14 days after Y-90 administration. A delay of 4 weeks will be permitted in case of toxicity. After yttrium Y 90 glass microspheres treatment, nivolumab will be administered intravenously (IV) over approximately 60 minutes every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent.
After completion of study treatment, patients are followed up 30 days after the last dose of nivolumab and again at 100 days after discontinuing study drug.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/Ib Study of Nivolumab in Combination With Therasphere (Yttrium-90) in Patients With Advanced Hepatocellular Carcinoma|
|Study Start Date :||July 2016|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||July 2020|
Experimental: Treatment (yttrium Y 90 glass microspheres, nivolumab)
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
Radiation: Yttrium Y 90 Glass Microspheres
Other Name: TheraSphere
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to 28 days after start of nivolumab ]The maximum tolerated dose (MTD) of nivolumab for combination treatment of nivolumab and Y-90 in this population will be defined as the highest dose that causes dose limiting toxicities (DLTs) in <2 of 6 patients.
- Objective Response Rate (ORR) [ Time Frame: At baseline and every 8 weeks for the first 13 months and then every 12 weeks up to 2 years ]Evaluate tumor response by assessing the proportion of patients with ORR (according to RECIST criteria) to the combination treatment of nivolumab with Y-90 by examining imaging scans.
- Incidence of Adverse Events [ Time Frame: Up to 100 days following the last administration of study drug ]Evaluate the toxicities (according to the NCCN CTCAE v4.03) and tolerability of nivolumab and y-90 in patients with advanced hepatocellular carcinoma.
- Progression Free Survival (PFS) [ Time Frame: Up to 24 weeks ]Evaluate the proportion of patients alive and progression free at 24 weeks.
- Disease Control Rate (DCR) [ Time Frame: At 24 months ]DCR will be determined at 24 months from the start of nivolumab treatment by the sum of complete response, partial response and stable response according to measurement of target and non-target lesions.
- PD-L1 protein expression [ Time Frame: At baseline ]Tumor tissue will be used to examine expression of PD-L1 protein on tumor cells.
- Expression level of biomarker of inflammatory/immune signature [ Time Frame: Up to 2 years ]Evaluate biomarker expression level using immunohistochemistry or flow cytometry.
- Circulating free DNA (cfDNA) mutation analyses [ Time Frame: Every 8 weeks for the first 24 weeks then every 16 weeks up to 2 years ]Change in clonal burden landscape will be analyzed to investigate its correlation with treatment response or development of resistance to treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02837029
|Contact: Study Coordinator||(312)firstname.lastname@example.org|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Aparna Kalyan, MBBS, FRACP 312-472-1234 Aparna.email@example.com|
|Principal Investigator: Aparna Kalyan, MBBS, FRACP|
|Sub-Investigator: Benedito Carneiro, MD, MS|
|Sub-Investigator: Jason Kaplan, MD|
|Sub-Investigator: Frank Giles, MD|
|Sub-Investigator: Young Chae, MD, MS|
|Sub-Investigator: Sunandana Chandra, MD, MS|
|Sub-Investigator: Mary Mulcahy, MD|
|Sub-Investigator: Al Benson, MD|
|Sub-Investigator: Halla Nimeiri, MD|
|Sub-Investigator: Sheetal Kircher, MD|
|Sub-Investigator: Laura Kulik, MD|
|Sub-Investigator: Robert Lewandowski, MD|
|Sub-Investigator: Riad Salem, MD|
|Principal Investigator:||Aparna Kalyan, MBBS, FRACP||Northwestern University|