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

NCT03655002 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 18245NCI-2018-01786P30CA033572
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief 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.

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

Outcome Measures

Primary Outcomes (2)

• Recommended phase II dose

  This is based on Simon?s MiniMax design.

  Up to 28 days

• Incidence of adverse events

  Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0.

  Up to 2 years

Secondary Outcomes (4)

• Overall response rate

  Up to 2 years

• Median progression-free survival (PFS)

  Time between study enrollment and when objective evidence of disease progression is documented, assessed up to 2 years

• PFS

  At 6 months

• Overall survival

  Time between study enrollment and death, assessed up to 2 years

Other Outcomes (3)

• Circulation T cell profiles

  Up to 2 years

• Tumor neoantigen

  Up to 2 years

• Circulating immune cell profiles circulating tumor deoxyribonucleic acid (DNA)

  Up to 2 years

Study Arms (1)

Treatment (nivolumab, cyclophosphamide, IRX-2)

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Biological: Cytokine-based Biologic Agent IRX-2; Biological: Nivolumab

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (nivolumab, cyclophosphamide, IRX-2)

Cytokine-based Biologic Agent IRX-2 BIOLOGICAL

Given SC

Also known as: IRX-2

Treatment (nivolumab, cyclophosphamide, IRX-2)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nivolumab, cyclophosphamide, IRX-2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.
• 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).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Texas Oncology at Baylor Charles A Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Cyclophosphamide; IRX 2; 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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Daneng Li

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

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: August 29, 2018
• First Posted: August 31, 2018
• Study Start: February 21, 2019
• Primary Completion (Estimated): March 2, 2027
• Study Completion (Estimated): March 2, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (3)