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Squamous Cell Carcinoma of the Oral CavityPhase 2INSPIRENCT02609386

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

A Phase 2 study testing IRX-2, Cyclophosphamide and Indomethacin in people with Squamous Cell Carcinoma of the Oral Cavity, run by Brooklyn ImmunoTherapeutics, LLC at 22 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
IRX-2, Cyclophosphamide and Indomethacin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
105 participants
Where
22 sitesin 4 countries
Study dates
11 Jan 2016to 28 Feb 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
Show all 32Show fewer
  • 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)
  • Any investigational agent within the previous 30 days.
  • Daily administration of systemic immunosuppressive therapy or corticosteroids (except in physiological doses for hormone deficiency) during the previous 30 days.
  • 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.
  • 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
  • Myocardial infarction within the last 3 months
  • Distant metastases (M1 disease).
  • Known infection with hepatitis B, hepatitis C, or HIV.
  • 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).
  • Clinically significant gastritis or peptic ulcer disease that would contraindicate the use of indomethacin.
  • Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months.
  • Allergy to ciprofloxacin (or other quinolones), acetylsalicylic acid, or indomethacin.
  • 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).
  • Prior axillary dissection.
  • Breastfeeding women.

Trial locations and contacts

22 sites in 4 countries.

22 sites in 4 countries

United States13 sites
  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University - Winship Cancer Center

    Atlanta, Georgia, 30322

  • University of Kentucky

    Lexington, Kentucky, 40506

  • University of Arkansas For Medical Sciences

    Little Rock, Arkansas, 72205

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Monter Cancer Center - North Shore LIJ

    New Hyde Park, New York, 11040

  • Lenox Hill Hospital

    New York, New York, 10075

  • University of Oklahoma

    Oklahoma City, Oklahoma, 73104

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Hospital of The University of Pennsylvania

    Philadelphia, Pennsylvania, 19106

  • Providence Cancer Center

    Portland, Oregon, 97209

  • Stanford University Medical Center

    Stanford, California, 94305

  • Banner University Medical Center

    Tucson, Arizona, 85742

Other trials in United States

Brazil7 sites
  • Hospital Erasto Gaertner

    Curitiba

  • Instituto Goiano de Oncologia e Hematologia (INGOH)

    Goiânia

  • Instituto do Câncer de Londrina

    Londrina

  • Instituto Nacional do Cancer (INCA)

    Rio de Janeiro

  • Hospital de Base de São José do Rio Preto

    São José do Vale do Rio Preto

  • Instituto Brasileiro de Controle do Câncer

    São Paulo

  • Instituto do Cancer do Estado de São Paulo - ICESP

    São Paulo

Other trials in Brazil

Canada1 site
  • Sunnybrook Research Institute

    Toronto

Other trials in Canada

United Kingdom1 site
  • Queen Elizabeth University Hospital Glasgow

    Glasgow

Other trials in United Kingdom

About this study

Official title: A Randomized Phase 2 Trial of Neoadjuvant and Adjuvant Therapy With the IRX 2 Regimen in Patients With Newly Diagnosed Stage II, III, or IVA Squamous Cell Carcinoma of the Oral Cavity

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.

Read the 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.

Being tested
IRX-2, Cyclophosphamide, Indomethacin, Zinc-containing multivitamin, Omeprazole
Keywords
Head and Neck Neoplasms, Immunotherapy, Cancer, Oral Cavity
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IRX-2Biological

    Also called Immunotherapy

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

  • CyclophosphamideDrug

    Also called Cytophosphane, Cytoxan

    Method of Administration: Cyclophosphamide is administered once by IV

  • IndomethacinDrug

    Also called NSAID, Indocin

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

  • Zinc-containing multivitaminDietary supplement

    Also called Zinc, Multi-vitamin

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

  • OmeprazoleDrug

    Also called Proton pump inhibitor, Prilosec

    Method of Administration: Omeprazole is administered orally for 21 days

Study groups in NCT02609386
Study groupRoleWhat they receive
Regimen 1ExperimentalIRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy.
Receives: Biological: IRX-2; Drug: Cyclophosphamide; Drug: Indomethacin; Dietary Supplement: Zinc-containing multivitamin; Drug: Omeprazole
Regimen 2Active comparatorRegimen 1 but without IRX-2
Receives: Drug: Cyclophosphamide; Drug: Indomethacin; Dietary Supplement: Zinc-containing multivitamin; Drug: Omeprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (2)
  1. Overall Survival (OS)- Number of Participants With an Event

    OS was defined as the time from randomization to death due to any cause.

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

  2. OS- Time to Event

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2015 (estimated)
  2. Study start11 Jan 2016
  3. Primary completion28 Feb 2022
  4. Study completion28 Feb 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02609386
Sponsor's protocol ID
IRX-2 2015-A
Acronym
INSPIRE
Status last verified
Jan 2024
First submitted
10 Sep 2015
Last updated
30 Jan 2024
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21284052
  • 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.

    PubMed 22057678
  • 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.

    PubMed 32738599

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IRX-2, Cyclophosphamide and Indomethacin in people with Squamous Cell Carcinoma of the Oral Cavity, run by Brooklyn ImmunoTherapeutics, LLC at 22 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, Brazil, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival (EFS)- Number of Participants With an Event (time frame: From randomization up until the data cut-off date of June 2, 2022 (approximately 76 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02609386, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.

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