NCT03655002

IRX-2, Cyclophosphamide, and Nivolumab in Treating Patients With Recurrent or Metastatic and Refractory Liver Cancer

A Phase 1b Trial of the IRX-2 Regimen and Nivolumab in Patients With Advanced Hepatocellular Cancer (HCC)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the side effects and best dose of IRX-2 when given together with cyclophosphamide and nivolumab in treating patients with liver cancer that has come back or spread to other parts of the body and does not response to treatment. Biological therapies, such as IRX-2, may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. Giving IRX-2, cyclophosphamide, and nivolumab may work better than the IRX?2 regimen alone in treating patients with hepatocellular carcinoma.

Detailed description

PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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. EXPLORATORY OBJECTIVES: 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.

Conditions

• Recurrent Hepatocellular Carcinoma
• Refractory Liver Carcinoma
• Stage IV Hepatocellular Carcinoma AJCC v8
• Stage IVA Hepatocellular Carcinoma AJCC v8
• Stage IVB Hepatocellular Carcinoma AJCC v8

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
BIOLOGICAL	Cytokine-based Biologic Agent IRX-2	Given SC
BIOLOGICAL	Nivolumab	Given IV

Timeline

• Start date: 2019-02-21
• Primary completion: 2026-03-30
• Completion: 2026-03-30
• First posted: 2018-08-31
• Last updated: 2025-06-17

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study