IRX-2, Cyclophosphamide, and Nivolumab in Treating Patients With Recurrent or Metastatic and Refractory Liver Cancer
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|ClinicalTrials.gov Identifier: NCT03655002|
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : August 11, 2021
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Hepatocellular Carcinoma Refractory Liver Carcinoma Stage IV Hepatocellular Carcinoma AJCC v8 Stage IVA Hepatocellular Carcinoma AJCC v8 Stage IVB Hepatocellular Carcinoma AJCC v8||Drug: Cyclophosphamide Biological: Cytokine-based Biologic Agent IRX-2 Biological: Nivolumab||Phase 1|
I. To determine the safety profile of combination IRX?2 regimen and nivolumab in anti?PD?1/PD?L1 naive patients who have failed or not tolerated at least one line of treatment.
I. To evaluate the overall response rate of IRX?2 regimen combined with nivolumab using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune modified RECIST criteria.
II. To evaluate the rate of 6?month progression?free survival in patients treated with combination IRX?2 regimen with nivolumab.
III. To evaluate median progression?free survival and overall survival.
I. To evaluate the circulating T cell profiles in patients before and after therapy with the combination IRX?2 regimen and nivolumab.
II. To explore identification of tumor tissue neoantigens through a multiplex proteomic assay (MHC?PepSeq) paired with tumor genomic and transcriptomic sequencing.
III. To explore putative biomarkers (including circulating tumor deoxyribonucleic acid [DNA] and immune cell profiles) in peripheral blood to generate hypotheses for response to treatment with combination IRX?2 regimen and nivolumab.
OUTLINE: This is a dose-escalation study of IRX-2.
Patients receive nivolumab intravenously (IV) over 30 minutes on day 1, cyclophosphamide IV on day 1, and IRX-2 subcutaneously (SC) for 10 days between days 4 and 15. Cycles repeat every 28 days for up to 18 months in the absence of disease progression or unacceptable toxicity. Patients receive booster IRX-2 SC at 3, 6, 9, 12, and 15 months.
After completion of study treatment, patients are followed up every 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Trial of the IRX-2 Regimen and Nivolumab in Patients With Advanced Hepatocellular Cancer (HCC)|
|Actual Study Start Date :||February 21, 2019|
|Estimated Primary Completion Date :||June 15, 2022|
|Estimated Study Completion Date :||June 15, 2022|
Experimental: Treatment (nivolumab, cyclophosphamide, IRX-2)
Patients receive nivolumab IV over 30 minutes on day 1, cyclophosphamide IV on day 1, and IRX-2 SC for 10 days between days 4 and 15. Cycles repeat every 28 days for up to 18 months in the absence of disease progression or unacceptable toxicity. Patients receive booster IRX-2 SC at 3, 6, 9, 12, and 15 months.
Biological: Cytokine-based Biologic Agent IRX-2
Other Name: IRX-2
- Recommended phase II dose [ Time Frame: Up to 28 days ]This is based on Simon?s MiniMax design.
- Incidence of adverse events [ Time Frame: Up to 2 years ]Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0.
- Overall response rate [ Time Frame: Up to 2 years ]Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Best response and the percentage of participants with a best response of partial response or better will be summarized.
- Median progression-free survival (PFS) [ Time Frame: Time between study enrollment and when objective evidence of disease progression is documented, assessed up to 2 years ]Per RECIST 1.1. PFS will be summarized using Kaplan?Meier methods.
- PFS [ Time Frame: At 6 months ]PFS rate will be summarized using Kaplan?Meier methods.
- Overall survival [ Time Frame: Time between study enrollment and death, assessed up to 2 years ]
- Circulation T cell profiles [ Time Frame: Up to 2 years ]
- Tumor neoantigen [ Time Frame: Up to 2 years ]Using multiplex proteomic assay.
- Circulating immune cell profiles circulating tumor deoxyribonucleic acid (DNA) [ Time Frame: Up to 2 years ]From peripheral blood.
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): NCT03655002
|United States, Arizona|
|HonorHealth Research Institute||Not yet recruiting|
|Scottsdale, Arizona, United States, 85258|
|Contact: Sunil Sharma 602-343-8402 firstname.lastname@example.org|
|Principal Investigator: Sunil Sharma|
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Daneng Li 626-256-4673 email@example.com|
|Principal Investigator: Daneng Li|
|United States, Texas|
|Texas Oncology at Baylor Charles A Sammons Cancer Center||Not yet recruiting|
|Dallas, Texas, United States, 75246|
|Contact: Andrew S. Paulson 214-370-1000 firstname.lastname@example.org|
|Principal Investigator: Andrew S. Paulson|
|Principal Investigator:||Daneng Li||City of Hope Medical Center|