IRX-2 Regimen in Patients With Newly Diagnosed Stage II, III, or IVA Squamous Cell Carcinoma of the Oral Cavity

NCT02609386 | Completed Phase 2 Results DMC

• 1 other identifier: IRX-2 2015-A
• Study Type: interventional
• Target: 105
• Locations: 4 countries
• Sites: 22

Brief Summary

The purpose of this study is to determine whether a pre-operative regimen of the study drug, IRX-2, a human cell-derived biologic with multiple active cytokine components, plus a single dose of cyclophosphamide, followed by 21 days of indomethacin, zinc-containing multivitamins, and omeprazole is active in treatment of oral cavity cancer. The regimen is intended to stimulate an immune response against the cancer.

Conditions

Squamous Cell Carcinoma of the Oral Cavity

Keywords

Head and Neck Neoplasms; Immunotherapy; Cancer; Oral Cavity

Outcome Measures

Primary Outcomes (2)

• Event-free Survival (EFS)- Number of Participants With an Event

  EFS is defined as the time from randomization until progression after surgery, or at surgery, if failure to resect gross disease, or at time of death from any cause after randomization.

  From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)

• EFS- Time to Event

  EFS is defined as the time from randomization until progression after surgery, or at surgery, if failure to resect gross disease, or at time of death from any cause after randomization. Assessment of progression/disease recurrence occurred by physical exam and annual imaging for the duration of the follow up portion of the study. Median EFS was estimated using the Kaplan-Meier method.

  From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)

Secondary Outcomes (2)

• Overall Survival (OS)- Number of Participants With an Event

  From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)

• OS- Time to Event

  From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)

Study Arms (2)

Regimen 1

EXPERIMENTAL

IRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy.

Biological: IRX-2; Drug: Cyclophosphamide; Drug: Indomethacin; Dietary Supplement: Zinc-containing multivitamin; Drug: Omeprazole

Regimen 2

ACTIVE COMPARATOR

Regimen 1 but without IRX-2

Drug: Cyclophosphamide; Drug: Indomethacin; Dietary Supplement: Zinc-containing multivitamin; Drug: Omeprazole

Interventions

IRX-2 BIOLOGICAL

Method of Administration: Administered for 10 days as subcutaneous bilateral injections in the upper neck.

Also known as: Immunotherapy

Regimen 1

Cyclophosphamide DRUG

Method of Administration: Cyclophosphamide is administered once by IV

Also known as: Cytophosphane, Cytoxan

Regimen 1; Regimen 2

Indomethacin DRUG

Method of Administration: Indomethacin is administered orally for 21 days.

Also known as: NSAID, Indocin

Regimen 1; Regimen 2

Zinc-containing multivitamin DIETARY_SUPPLEMENT

Method of Administration: Zinc-containing multivitamin is administered orally for 21 days.

Also known as: Zinc, Multi-vitamin

Regimen 1; Regimen 2

Omeprazole DRUG

Method of Administration: Omeprazole is administered orally for 21 days

Also known as: Proton pump inhibitor, Prilosec

Regimen 1; Regimen 2

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed (histology or cytology) clinical Stage II, III, or IVA squamous cell cancer of the oral cavity (excluding lip). Subjects must be staged using AJCC Cancer Staging Manual Edition 7.0 (appendices 1 and 2).
• Disease surgically resectable with curative intent
• Hematological function: hemoglobin \>9 g/dL; lymphocyte count \>0.50 x 109/L; neutrophil count \>1.5 x 109/L; platelet count \>100 x 109/L
• Hepatic function: serum albumin \>3.0 g/dL; aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \<3x the upper limits of normal (ULN); alkaline phosphatase \<2x the ULN
• Prothrombin time (PT) and partial thromboplastin time (PTT) \< 1.4x the ULN
• Calculated creatinine clearance \> 50 mL/minute (Appendix 4)
• At least 18 years of age
• Willing and able to give informed consent and adhere to protocol therapy
• Karnofsky performance status (KPS) \>=70%
• Females of childbearing potential (not surgically sterile or less than 12 months post-menopausal) must be able and willing to use a highly effective form of pregnancy prevention from the time of screening, during the study and 30 days after last dose of study regimen. Males with a partner of childbearing potential must use condoms with spermicide from the date of screening to 30 days after their last dose of study regimen
• Negative urine/serum pregnancy test, if applicable

You may not qualify if:

• Prior surgery, radiation therapy, or chemotherapy other than biopsy or emergency procedure required for supportive care of this oral cavity cancer.
• Any medical contraindications or previous therapy that would preclude treatment with either IRX 2 Regimen 1 or 2 or the surgery, reconstruction or adjuvant therapy required to treat the oral tumor appropriately
• Live vaccines should ideally not be administered to any patients undergoing treatment with chemotherapy or immunotherapy, but if need be, they should be administered \>4 months prior to the initiation of treatment or \>4 months after the completion of all treatment
• Inactivated vaccines should precede the initiation of any study regimen and/or standard adjuvant therapy by at least 2 weeks, but preferably 4 weeks or longer
• Clinical status of either subject or tumor such that administration of 21 day neoadjuvant IRX-2 Regimen 1 or 2 before surgery would be medically inappropriate
• Tumor of the oropharynx
• Tumor involvement of the following sites or any of these signs or symptoms likely to be associated with T4b cancer:
• involvement of pterygopalatine fossa, maxillary sinus, or facial skin;.
• gross extension of tumor to the skull base;
• pterygoid plate erosion;
• sphenoid bone or foramen ovale involvement;
• direct extension to involve prevertebral fascia;
• extension to superior nasopharynx or Eustachian tube;
• direct extension into the neck with involvement of the deep neck musculature (neck node fixation);
• suspected invasion (encasement) of the common or internal carotid arteries. Encasement will be assessed radiographically and will be defined as tumor surrounding the carotid artery 270º or greater;

Sponsors & Collaborators

• Brooklyn ImmunoTherapeutics, LLC: lead

Study Sites (22)

Banner University Medical Center

Tucson, Arizona, 85742, United States

Location

University of Arkansas For Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Emory University - Winship Cancer Center

Atlanta, Georgia, 30322, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Monter Cancer Center - North Shore LIJ

New Hyde Park, New York, 11040, United States

Location

Lenox Hill Hospital

New York, New York, 10075, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Cancer Center

Portland, Oregon, 97209, United States

Location

Hospital of The University of Pennsylvania

Philadelphia, Pennsylvania, 19106, United States

Location

Hospital Erasto Gaertner

Curitiba, Brazil

Location

Instituto Goiano de Oncologia e Hematologia (INGOH)

Goiânia, Brazil

Location

Instituto do Câncer de Londrina

Londrina, Brazil

Location

Instituto Nacional do Cancer (INCA)

Rio de Janeiro, Brazil

Location

Hospital de Base de São José do Rio Preto

São José do Vale do Rio Preto, Brazil

Location

Instituto Brasileiro de Controle do Câncer

São Paulo, Brazil

Location

Instituto do Cancer do Estado de São Paulo - ICESP

São Paulo, Brazil

Location

Sunnybrook Research Institute

Toronto, Canada

Location

Queen Elizabeth University Hospital Glasgow

Glasgow, United Kingdom

Location

Related Publications (3)

• Wolf GT, Fee WE Jr, Dolan RW, Moyer JS, Kaplan MJ, Spring PM, Suen J, Kenady DE, Newman JG, Carroll WR, Gillespie MB, Freeman SM, Baltzer L, Kirkley TD, Brandwein HJ, Hadden JW. Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer. Head Neck. 2011 Dec;33(12):1666-74. doi: 10.1002/hed.21660. Epub 2011 Jan 31.

  PMID: 21284052 BACKGROUND

• Berinstein NL, Wolf GT, Naylor PH, Baltzer L, Egan JE, Brandwein HJ, Whiteside TL, Goldstein LC, El-Naggar A, Badoual C, Fridman WH, White JM, Hadden JW. Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen. Cancer Immunol Immunother. 2012 Jun;61(6):771-82. doi: 10.1007/s00262-011-1134-z. Epub 2011 Nov 6.

  PMID: 22057678 BACKGROUND

• Wolf GT, Liu S, Bellile E, Sartor M, Rozek L, Thomas D, Nguyen A, Zarins K, McHugh JB; INSPIRE Trial Clinical Investigators. Tumor infiltrating lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma: Interim findings from the INSPIRE trial. Oral Oncol. 2020 Dec;111:104928. doi: 10.1016/j.oraloncology.2020.104928. Epub 2020 Jul 29.

  PMID: 32738599 DERIVED

Related Links

• Sponsor's website

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Neoplasms

Interventions

IRX 2; Immunotherapy; Cyclophosphamide; Indomethacin; Anti-Inflammatory Agents, Non-Steroidal; Zinc; Geritol; Omeprazole; Proton Pump Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action

Limitations and Caveats

One of the initial secondary objectives of the study was to compare the feasibility of each booster regimen (Regimen 1 vs Regimen 2) post-surgery. However, as a significant number of patients were unable to receive booster treatments due to tolerability issues and/or their post-surgery/post-adjuvant chemoradiation therapy status, booster regimens were discontinued and analysis of booster feasibility was not performed due to insufficient data for a meaningful, statistically sound analysis.

Results Point of Contact

• Title: VP of Quality
• Organization: Eterna Therapeutics

info@eternatx.com

212-582-1199

Study Officials

• Gregory T Wolf, MD, FACS

  University of Michigan Hospitals

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2015
• First Posted: November 20, 2015
• Study Start: January 11, 2016
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: January 30, 2024
• Results First Posted: January 30, 2024

Record last verified: 2024-01

Locations

BR (7); US (13); GB (1); CA (1)