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

Running, not enrolling · Phase 1

Conditions studied: Recurrent Hepatocellular Carcinoma, Refractory Liver Carcinoma, Stage IV Hepatocellular Carcinoma AJCC v8, Stage IVA Hepatocellular Carcinoma AJCC v8, Stage IVB Hepatocellular Carcinoma AJCC v8

In brief

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.

Key facts

Study ID

NCT03655002

Run by

City of Hope Medical Center

People needed

8

Starts

2019-02-21

Expected to finish

2027-03-02

Last updated by the study team

2026-04-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients with histologically or cytologically confirmed recurrent or metastatic hepatocellular carcinoma (HCC).
• Patients must have recurrent or metastatic HCC that are not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
• Must have failed or not tolerated at least one line of treatment for advanced HCC.
• Willing and able to give informed consent and adhere to protocol therapy; written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol?related procedures, including screening evaluations.
• Up to three prior systemic therapy regimens for recurrent and/or metastatic disease.
• Eastern Cooperative Oncology Group (ECOG) 0?1.
• Have a Child?Pugh class A liver score within 7 days of first dose of study drug.
• Hemoglobin > 8 g/dL.
• Absolute neutrophil count (ANC) > 1,200 x 10\^9/mL.
• Platelet count > 60 x 10\^9/mL.
• Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 5 x ULN.
• Serum albumin > 3.0 g/dL.
• Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.5 x the ULN.
• Measured creatinine clearance (CL) > 40 mL/min or calculated creatinine clearance CL > 40 mL/min by the Cockcroft?Gault formula 10 or by 24?hour urine collection for determination of creatinine clearance.
• Palliative radiation therapy is allowed to non?target lesions at the discretion of the treating physician.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as outlined in RECIST version 1.1.
• Life expectancy of greater than 3 months.
• Subjects with chronic infection by hepatitis C virus (HCV) who are untreated are allowed on study. In addition, subjects with successful HCV treatment (defined as sustained virologic response [SVR] 12 or SVR 24) are allowed as long as 4 weeks have passed between completion of HCV therapy and start of study drug.
• Subjects with hepatitis B virus (HBV) may only be enrolled if their hepatitis is judged clinically stable by the investigator.
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment.
• Body weight > 30 Kg.

You may not qualify if…

• Prior exposure to PD?1/PD?L1 inhibitors.
• Prior exposure to IRX?2 regimen.
• Radiation therapy with a curable intent within 30 days of first dose of study treatment is excluded. However, radiation therapy with a palliative intent is allowed as long as treatment with study medication occurs >= 14 days after last dose of radiation and as long as there is at least 1 evaluable non?treated target lesion remaining.
• Any medical contraindications or previous therapy that would preclude treatment with the IRX 2 regimen or nivolumab including the following:
• Patients with allergies to ciprofloxacin or phytohemagglutinin (PHA).
• Patients with evidence of pre?existing myelosuppression, myelodysplasia or hemorrhagic cystitis.
• Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients with grade >= 2 neuropathy will be evaluated on a case?by?case basis after consultation with the study physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with IRX?2, nivolumab may be included only after consultation with the study physician.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 2 years may be included but only after consultation with the study physician.
• Patients with celiac disease controlled by diet alone.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of nivolumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroid or local steroid injections (e.g., intra articular injection).
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication).
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of nivolumab.
• Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease. Patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for systemic treatments need not be excluded.
• Myocardial infarction within the last 3 months.
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Has untreated active Hepatitis B.

Where it is running

• HonorHealth Research Institute — Scottsdale, Arizona, United States
• City of Hope Medical Center — Duarte, California, United States
• Texas Oncology at Baylor Charles A Sammons Cancer Center — Dallas, Texas, United States

Full record on ClinicalTrials.gov

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