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

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ClinicalTrials.gov Identifier: NCT02609386
Recruitment Status : Recruiting
First Posted : November 20, 2015
Last Update Posted : November 14, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Oral Cavity Biological: IRX-2 Drug: Cyclophosphamide Drug: Indomethacin Dietary Supplement: Zinc-containing multivitamin Drug: Omeprazole Phase 2

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : December 2015
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : December 2019
Arms and Interventions

Arm Intervention/treatment
Experimental: Regimen 1
IRX Regimen with IRX-2, cyclophosphamide, indomethacin, zinc-containing multivitamin, and omeprazole as neoadjuvant and adjuvant therapy.
Biological: IRX-2
Method of Administration: Administered for 10 days as subcutaneous bilateral injections in the upper neck.
Other Name: Immunotherapy
Drug: Cyclophosphamide
Method of Administration: Cyclophosphamide is administered once by IV
Other Names:
  • Cytophosphane
  • Cytoxan
Drug: Indomethacin
Method of Administration: Indomethacin is administered orally for 21 days.
Other Names:
  • Indocin
Dietary Supplement: Zinc-containing multivitamin
Method of Administration: Zinc-containing multivitamin is administered orally for 21 days.
Other Names:
  • Zinc
  • Multi-vitamin
Drug: Omeprazole
Method of Administration: Omeprazole is administered orally for 21 days
Other Names:
  • Proton pump inhibitor
  • Prilosec
Active Comparator: Regimen 2
Regimen 1 but without IRX-2
Drug: Cyclophosphamide
Method of Administration: Cyclophosphamide is administered once by IV
Other Names:
  • Cytophosphane
  • Cytoxan
Drug: Indomethacin
Method of Administration: Indomethacin is administered orally for 21 days.
Other Names:
  • Indocin
Dietary Supplement: Zinc-containing multivitamin
Method of Administration: Zinc-containing multivitamin is administered orally for 21 days.
Other Names:
  • Zinc
  • Multi-vitamin
Drug: Omeprazole
Method of Administration: Omeprazole is administered orally for 21 days
Other Names:
  • Proton pump inhibitor
  • Prilosec

Outcome Measures

Primary Outcome Measures :
  1. Change in Event-Free Survival from baseline [ Time Frame: At each study visit after surgery: at 3,6,9,12,15,18, 21,24,30,36,42,48 months ]
    To determine if the event-free survival (EFS) of subjects treated with Regimen 1 is longer than for subjects treated with Regimen 2

Secondary Outcome Measures :
  1. Change in Overall Survival from baseline [ Time Frame: At each study visit after surgery: at 3,6,9,12,15,18,21,24,30,36,42,48 months ]
    To determine if OS of subjects treated with Regimen 1 is longer than for subjects treated with Regimen 2

  2. Change in safety from baseline in each Regimen using a pre-approved questionnaire (case report form) [ Time Frame: At each study visit after surgery: at 3,6,9,12,15,18,21,24,30,36,42,48 months ]
    Medical professional will assess according to pre-specified list for patient response, lab results, adverse events, etc. at pre-specified intervals. Pain to be assessed using NCI Criteria grade from the following: None, Mild, Moderate or Severe

  3. Compare the feasibility of each Booster Regimen [ Time Frame: Several procedures will be completed prior to the initiation of each Booster Regimen (3,6,9, and 12 months after surgery) to evaluate any ongoing adverse events and the overall clinical status of the subject. ]
    IRX-2 Booster Regimens have not been previously studied. Since subjects receiving the Booster Regimens will be post-operative and many will have also received adjuvant radiation or chemotherapy, their ability to receive and tolerate an even shorter IRX-2 regimen will be evaluated in this study.

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02609386

Contact: IRX INSPIRE INSPIRE@IRXTherapeutics.com

  Hide Study Locations
United States, Arizona
Banner University Medical Center Recruiting
Tucson, Arizona, United States, 85742
Contact: Kiley Raica       kileyraica@email.arizona.edu   
Principal Investigator: Audrey Erman, MD         
United States, Arkansas
University of Arkansas For Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Kathryn Allen       KGAllen@uams.edu   
Principal Investigator: Emre Vural, MD         
United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Gina Tse       tse_g@med.usc.edu   
Principal Investigator: Jorge Nieva, MD         
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Nikita Bedi       nbedi@stanford.edu   
Principal Investigator: Michael Kaplan, MD         
United States, District of Columbia
Washington DC VA Medical Center Withdrawn
Washington, District of Columbia, United States, 20422
United States, Florida
H Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Brian Trank       brian.trank@moffitt.org   
Principal Investigator: Christine Chung, MD         
United States, Georgia
Emory University - Winship Cancer Center Recruiting
Atlanta, Georgia, United States, 30322
Contact: Nikki Hirsh       nikkihirsh@emory.edu   
Principal Investigator: Mihir Patel, MD         
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40506
Contact: Joy Kimbrough       jidiaz0@uky.edu   
Principal Investigator: Joseph Valentino, MD         
United States, Massachusetts
Lahey Hospital & Medical Center Withdrawn
Burlington, Massachusetts, United States, 01805
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Terri Jobkar       tjobkar@med.umich.edu   
Principal Investigator: Jeffrey Moyer, MD         
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68114
Contact: Kathryn Bartz       kathryn.bartz@nmhs.org   
Principal Investigator: Aru Panwar, MD         
University of Nebraska Medical Center Withdrawn
Omaha, Nebraska, United States, 68198
United States, New York
Monter Cancer Center - North Shore LIJ Recruiting
New Hyde Park, New York, United States, 11040
Contact: Vimla Singh       vsingh11@northwell.edu   
Principal Investigator: Dennis Kraus, MD         
Lenox Hill Hospital Recruiting
New York, New York, United States, 10075
Contact: Christina Persaud       Cpersaud9@northwell.edu   
Principal Investigator: Dennis Kraus, MD         
United States, Oklahoma
University of Oklahoma Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Nancy Cleaver       Nancy-cleaver@ouhsc.edu   
Principal Investigator: Greg Krempl, MD         
United States, Oregon
Providence Cancer Center Recruiting
Portland, Oregon, United States, 97209
Contact: George Morris       George.morris@providence.org   
Principal Investigator: Bryan Bell, MD DDS FACS         
United States, Pennsylvania
Hospital of The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19106
Contact: Samantha Jaffe       samantha.jaffe@uphs.upenn.edu   
Principal Investigator: Jason Newman, MD         
Fundacão Pio XII Hospital do Câncer de Barretos Recruiting
Barretos, Brazil
Contact: Lucimara Rocha       lucimara.pesquisaclinica@hcancerbarretos.com.br   
Principal Investigator: Pedro Marchi         
Hospital Erasto Gaertner Recruiting
Curitiba, Brazil
Contact: Mariana Bordinhao       mbordinhao@erastogaertner.com.br   
Principal Investigator: Fabricio Oliveira         
Instituto Goiano de Oncologia e Hematologia (INGOH) Recruiting
Goiânia, Brazil
Contact: Mara Rocha       startresearch@hotmail.com   
Principal Investigator: Wanessa A Martins         
Instituto do Câncer de Londrina Recruiting
Londrina, Brazil
Contact: Mariana Geroldi       pesquisaclinicahcl@gmail.com   
Principal Investigator: Clodoaldo Campos         
Hospital São Lucas (PUC) Porto Alegre Recruiting
Pôrto Alegre, Brazil
Contact: Amanda Rocha       Amanda.darocha@cpors.com   
Principal Investigator: Ana Gelatti         
Instituto Nacional do Cancer (INCA) Recruiting
Rio de Janeiro, Brazil
Contact: Giovana Kovaleski       giovana.kovaleski@inca.gov.br   
Principal Investigator: Ana Victorino         
Hospital de Base de São José do Rio Preto Recruiting
São José do Rio Prêto, Brazil
Contact: Virginia Cappi       virginiacappi@gmail.com   
Principal Investigator: Gustavo Girotto         
Instituto Brasileiro de Controle do Câncer Recruiting
São Paulo, Brazil
Contact: Juliana Mauri       julianamauri@ibcc.org.br   
Principal Investigator: Felipe Cruz         
Instituto do Cancer do Estado de São Paulo - ICESP Recruiting
São Paulo, Brazil
Contact: Rita Tavares       rita.tavares@hc.fm.usp.br   
Principal Investigator: Claudio Cernea         
Sunnybrook Research Institute Recruiting
Toronto, Canada
Contact: Sharon Braganza       sharon.braganza@sunnybrook.ca   
Principal Investigator: Kevin Higgins, MD         
Azienda Ospedaliera Santi Paolo e Carlo Recruiting
Milano, Italy
Contact: Gabriela Cassinelli       gabriela.cassinelli4@gmail.com   
Principal Investigator: Daris Ferrari         
Istituto Nazionale dei Tumori Recruiting
Milano, Italy
Contact: Alessandro Lorizzo       Alessandro.Lorizzo@istitutotumori.mi.it   
Principal Investigator: Lisa Licitra         
Hospital de La Santa Creu i Sant Pau Recruiting
Barcelona, Spain
Contact: Merce Garcia Belinchón       MGarcia@santpau.cat   
Principal Investigator: Antonio Lopez         
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Sandra Tijeras       stijeras@vhio.net   
Principal Investigator: Irene Braña         
Hospital Ramón y Cajal Recruiting
Madrid, Spain
Contact: Xaqueline Cid Sáinz       xaqueline_cid_sainz@msn.com   
Principal Investigator: Ainara Soria         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: Sara Gómez Abecia       abecia@h12o.es   
Principal Investigator: Lara Iglesias Docampo         
Hospital General de Valencia Recruiting
Valencia, Spain
Contact: Belen Vázquez Blanco       vazquez_bel@gva.es   
Principal Investigator: Alfonso Berrocal         
Universitätsspital Basel Recruiting
Basel, Switzerland
Contact: Sara Hasler       sara.hasler@usb.ch   
Principal Investigator: Laurent Muller         
Inselspital Bern Recruiting
Bern, Switzerland
Contact: Antje Kramer       antje.kramer@insel.ch   
Principal Investigator: Roland Giger         
Sponsors and Collaborators
IRX Therapeutics
Principal Investigator: Gregory T Wolf, MD, FACS University of Michigan Hospitals
More Information

Additional Information:
Responsible Party: IRX Therapeutics
ClinicalTrials.gov Identifier: NCT02609386     History of Changes
Other Study ID Numbers: IRX-2 2015-A
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: November 14, 2017
Last Verified: November 2017

Keywords provided by IRX Therapeutics:
Head and Neck Neoplasms
Oral Cavity

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Proton Pump Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Trace Elements
Growth Substances
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents