Efficacy and Safety Study of Leukocyte Interleukin,Injection (LI) to Treat Cancer of the Oral Cavity
Condition: Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Soft Palate
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Intervention: LI; Cyclophosphamide; Indomethacin; Zinc; Surgery; Cisplatin; Radiotherapy
Intervention description: LI 400 IU (2.0mL total daily) 1.0 mL peritumoral, 1.0 mL perilymphatic 5x weekly x3 consecutive weeks administered as neoadjuvant therapy prior to SOC, (surgery followed by radiation or concurrent radiochemotherapy with cisplatin 100 mg/m^2 intravenously x3) to determine if LI plus CIZ affects the 3-5 year overall survival.; Cyclophosphamide was administered IV bolus (one time only) at a dose of 300mg/m^2 three days prior to beginning treatment with LI. Standard of care (SOC) for previously untreated squamous cell carcinoma of the head and neck is currently surgery followed by radiotherapy (60-70Gy in 30 to 35 fractions over 6 to 7 weeks) for higher risk subjects (subjects determined at surgery to have adverse features per the National Comprehensive Cancer Network (NCCN) guidelines, such as, positive surgical margins, 2 or more clinically positive nodes or extracapsular nodal spread, etc. that would pre-dispose them for higher risk of recurrence) radiotherapy is combined with concurrent chemotherapy (cisplatin 100mg/m^2 intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy.; One 25mg capsule of indomethacin was self administered orally (BID) beginning on day one of LI treatment daily until the day before surgery.; One capsule daily self administered beginning on day one of treatment with LI until one day before surgery; Excise tumor and nodes; Cisplatin was administered 100mg/m^2 IV concurrent with radiotherapy. The chemotherapy agent (cisplatin 100mg/m^2) was administered intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy.; Total 60 to 70 Gy (2Gy per day) in 30 to 35 fractions over 6 to 7 weeks to subjects determined at surgery to be at lower risk for recurrence (per NCCN guidelines). For subjects determined at surgery to be at higher risk for recurrence due to having positive surgical margins, 2 or more clinically positive nodes or extracapsular nodal spread etc. (per NCCN guidelines), radiotherapy (as above) is combined with concurrent chemotherapy (cisplatin 100 mg/m^2) intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy.
Intervention MeSH terms: Indomethacin; Cyclophosphamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 928.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study was to determine whether LI administered in combination with
      cyclophosphamide, indomethacin and zinc in a multivitamin (CIZ) combination prior to standard
      of care therapy (surgery followed by radiotherapy or concurrent radiochemotherapy) is safe
      and will increase the overall survival of subjects with previously untreated locally advanced
      primary squamous cell carcinoma of the oral cavity or soft palate at a median of 3 to 5 years
    

Eligibility criteria:

        Inclusion Criteria (main):

          -  Untreated SCCHN of oral cavity (anterior tongue, floor of mouth, cheek)/soft palate,
             categories T1N1-2M0,T2N1-2M0,T3N0-2M0,T4N0-2M0 (T4 allowed only if invasion of
             mandible is negligible i. e. 5mm or less) scheduled for SOC

          -  Primary tumor and any positive node(s) measurable in 2 dimensions

          -  Normal immune function

          -  No immunosuppressives with 1 year of entry

          -  KPS>70/100

          -  Age>18

          -  Male or Female (non-pregnant)

          -  Life expectancy >6 months

          -  Able to take oral medication

          -  Able to provide informed consent

        Exclusion Criteria (main):

          -  Subjects to be treated with other than SOC

          -  Tumor invasion of bone (also see inclusion criteria)

          -  Tumor classifications T1N0, T2N0, T4N3, any TN classification with M1

          -  Tumors in locations other than those specified in inclusion criteria

          -  Active peptic ulcer (or on full-dose therapeutic anti-coagulants)

          -  Prior resection of jugular nodes ipsilateral to tumor

          -  Acute or chronic viral, bacterial immune or other disease associated with abnormal
             immune function

          -  Subjects on hemodialysis or peritoneal dialysis; or having a history of

          -  History of asthma, allergy to fluoroquinolone antibiotics, congestive heart failure,
             or on hemodialysis or peritoneal dialysis

          -  Any condition that in the opinion of the investigator would cause the subject to be
             unable to participate or tolerate the protocol regimen

          -  Failure to meet inclusion criteria