IRX-2 Regimen in Patients With Newly Diagnosed Stage II, III, or IVA Squamous Cell Carcinoma of the Oral Cavity
Condition: Squamous Cell Carcinoma of the Oral Cavity
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Intervention: IRX-2; Cyclophosphamide; Indomethacin; Zinc-containing multivitamin; Omeprazole
Intervention description: Method of Administration: Administered for 10 days as subcutaneous bilateral injections in the upper neck.; Method of Administration: Cyclophosphamide is administered once by IV; Method of Administration: Indomethacin is administered orally for 21 days.; Method of Administration: Zinc-containing multivitamin is administered orally for 21 days.; Method of Administration: Omeprazole is administered orally for 21 days
Intervention MeSH terms: Zinc; Indomethacin; Cyclophosphamide; Omeprazole; Proton Pump Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 105.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Neoplasms; Immunotherapy; Cancer; Oral Cavity

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.
    

Eligibility criteria:

        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.