Phase III Study of LI [Multikine®] Plus SOC (Surgery + Radiotherapy or Surgery + Concurrent Radiochemotherapy) in Subjects With Advanced Primary Squamous Cell Carcinoma of the Oral Cavity/Soft Palate vs. SOC Only
Head and neck carcinomas constitute about 5% of all cancers annually worldwide. In the US
there are about 37,000 new cases annually. Ninety percent are advanced primary squamous cell
carcinoma (SCCHN). Approximately 2/3 of SCCHN patients present on their first visit with
locally advanced disease. The median 3 year overall survival(OS) for these patients with
existing standard of care (SOC) therapies - surgery followed by radiotherapy or combined
radiochemotherapy - is between 52 and 55%; the 5 year OS is 43%. There are clearly a large
number of SCCHN patients not well served by available modalities.
Regional intra or perilymphatic and/or intratumoral or peritumoral low dose cytokine therapy
may have important therapeutic effects in SCCHN patients and constitute an additional
anti-tumor mechanism of action different and distinct from current SOC. Leukocyte
Interleukin Injection (LI) [Multikine]contains a defined mixture of naturally derived
cytokines and chemokines with demonstrated safety and immunomodulatory activity in animals
and in man in Phase 1 and 2 clinical trials. LI was administered prior to SOC and in
combination with low non-chemotherapeutic doses of cyclophosphamide, indomethacin, and zinc
(CIZ) in studies with LI. The results of these studies indicate that the local/regional
injection of mixed interleukins (LI) with CIZ prior to SOC can overcome local
immunosuppression, break tumor tolerance to tumor antigens and allow for a sustainable and
effective anti-tumor immune response.
LI is being tested in this large, global, multinational Phase III clinical trial to develop
definitive proof of its efficacy and safety in treating SCCHN. The trial is an open-label
randomized multi-center controlled study of LI + CIZ + SOC in subjects with advanced primary
SCCHN of the oral cavity/soft palate vs. SOC [The Comparator Arms for, Overall Survival, the
Primary End Point of this Study].
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Survival (OS) in LI + CIZ + SOC vs. SOC
OS will be assessed using Kaplan-Meier life-table and compared using a logrank test and confirmed further with tumor stage location and geographic stratified log rank tests. The unstratified logrank test constitutes the primary analysis. A two-sided p-value of 0.05 or less will be considered statistically significant for comparing the two groups. Interim analyses will be performed throughout the study to assess safety, sample size and futility.
Eyal Talor, PhD
United States: Food and Drug Administration
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