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

Phase 2

Completed

• Conditions: Squamous Cell Carcinoma of the Oral Cavity
• Interventions: Biological: IRX-2; Drug: Cyclophosphamide; Drug: Indomethacin; Dietary Supplement: Zinc-containing multivitamin; Drug: Omeprazole

• Registration Number: NCT02609386
• Lead Sponsor: Brooklyn ImmunoTherapeutics, LLC

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.

Detailed Description

This study will assess the activity and safety of the IRX Regimen in participants with newly diagnosed, untreated, surgically resectable squamous cell cancer of the oral cavity. Participants will be randomly assigned to receive either Regimen 1: IRX-2 + cyclophosphamide + indomethacin + zinc + omeprazole, or Regimen 2: cyclophosphamide + indomethacin + zinc + omeprazole.

The primary study hypothesis is that the Regimen 1 with IRX-2 prolongs event-free survival and overall survival when compared to Regimen 2 without IRX-2.

Subjects will be randomized to either Regimen 1 or Regimen 2 on a 2:1 basis and treated prior to surgery.

Study Timeline

• Study First Submitted: 2015-09-10
• Study First Submitted QC: 2015-11-17
• Study First Posted: 2015-11-20
• Study Start: 2016-01-11
• Primary Completion: 2022-02-28
• Study Completion: 2022-02-28
• Results First Submitted: 2023-12-04
• Status Verified: 2024-01
• Results First Submitted QC: 2024-01-23
• Last Update Submitted: 2024-01-23
• Results First Posted: 2024-01-30
• Last Update Posted: 2024-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

1. 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).
2. Disease surgically resectable with curative intent
3. 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
4. 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
5. Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.4x the ULN
6. Calculated creatinine clearance > 50 mL/minute (Appendix 4)
7. At least 18 years of age
8. Willing and able to give informed consent and adhere to protocol therapy
9. Karnofsky performance status (KPS) >=70%
10. 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
11. Negative urine/serum pregnancy test, if applicable

Exclusion Criteria

1. Prior surgery, radiation therapy, or chemotherapy other than biopsy or emergency procedure required for supportive care of this oral cavity cancer.

2. 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

3. 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

4. Tumor of the oropharynx

5. 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;
   • direct extension of neck disease to involve the external skin;
   • direct extension to mediastinal structures;
   • regional metastases to the supraclavicular neck (low level IVB or VB)

6. Any investigational agent within the previous 30 days.

7. Daily administration of systemic immunosuppressive therapy or corticosteroids (except in physiological doses for hormone deficiency) during the previous 30 days.

8. Chronic anticoagulation, not including aspirin, but including heparins, warfarin, oral anticoagulation or other platelet function inhibitors, that can not, in the documented opinion of the investigator, safely be interrupted from at least 2 days prior to the initiation of the study regimen until after surgical resection of the tumor.

9. 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 surgical treatment of their tumor need not be excluded

10. Myocardial infarction within the last 3 months

11. Distant metastases (M1 disease).

12. Known infection with hepatitis B, hepatitis C, or HIV.

13. Signs or symptoms of systemic bacterial infection (use of antibiotics to treat superficial infection or contamination of tumor shall not, by itself, be considered evidence of infection).

14. Clinically significant gastritis or peptic ulcer disease that would contraindicate the use of indomethacin.

15. Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months.

16. Allergy to ciprofloxacin (or other quinolones), acetylsalicylic acid, or indomethacin.

17. Previous diagnosis of invasive cancer from which the individual is NOT disease-free AND that has required treatment within the past 5 years, except for superficial skin, cervical cancer in-situ, well-differentiated thyroid or early stage prostate or bladder cancer (i.e., treatment with curative intent and long term disease-free expectations).

18. Prior axillary dissection.

19. Breastfeeding women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regimen 1	Zinc-containing multivitamin	IRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy.
Regimen 1	IRX-2	IRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy.
Regimen 1	Omeprazole	IRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy.
Regimen 2	Zinc-containing multivitamin	Regimen 1 but without IRX-2
Regimen 1	Cyclophosphamide	IRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy.
Regimen 1	Indomethacin	IRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy.
Regimen 2	Cyclophosphamide	Regimen 1 but without IRX-2
Regimen 2	Indomethacin	Regimen 1 but without IRX-2
Regimen 2	Omeprazole	Regimen 1 but without IRX-2

Primary Outcome Measures

Name	Time	Method
Event-free Survival (EFS)- Number of Participants With an Event	From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)	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.
EFS- Time to Event	From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)	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.

Secondary Outcome Measures

Name	Time	Method
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 was defined as the time from randomization to death due to any cause.
OS- Time to Event	From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)	OS was defined as the time from randomization to death due to any cause. Data for partipants who were alive at the end of the study were censored at the last known alive date. Median OS was estimated using the Kaplan-Meier method.

Trial Locations

Locations (22)

Queen Elizabeth University Hospital Glasgow; 🇬🇧 Glasgow, United Kingdom

Monter Cancer Center - North Shore LIJ; 🇺🇸 New Hyde Park, New York, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Lenox Hill Hospital; 🇺🇸 New York, New York, United States

Hospital Erasto Gaertner; 🇧🇷 Curitiba, Brazil

Instituto Goiano de Oncologia e Hematologia (INGOH); 🇧🇷 Goiânia, Brazil

Instituto Nacional do Cancer (INCA); 🇧🇷 Rio de Janeiro, Brazil

University of Arkansas For Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Instituto do Câncer de Londrina; 🇧🇷 Londrina, Brazil

Hospital de Base de São José do Rio Preto; 🇧🇷 São José do Rio Prêto, Brazil

Sunnybrook Research Institute; 🇨🇦 Toronto, Canada

Banner University Medical Center; 🇺🇸 Tucson, Arizona, United States

Instituto Brasileiro de Controle do Câncer; 🇧🇷 São Paulo, Brazil

Instituto do Cancer do Estado de São Paulo - ICESP; 🇧🇷 São Paulo, Brazil

USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

University of Oklahoma; 🇺🇸 Oklahoma City, Oklahoma, United States

Providence Cancer Center; 🇺🇸 Portland, Oregon, United States

Hospital of The University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Emory University - Winship Cancer Center; 🇺🇸 Atlanta, Georgia, United States