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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 928
- 试验地点
- 102
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
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
详细描述
Head and neck carcinomas constitute about 5% of all cancers annually worldwide. In the US there are about 65,000 new cases annually. Ninety percent are squamous cell carcinoma of the head and neck (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 concurrent radiochemotherapy - is estimated to be between 52 and 55%; the 5 year OS is approximately 43%. There are clearly many 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 I and Phase II clinical trials. LI is 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 was 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 arm]. OS is the primary efficacy endpoint.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
LI + CIZ + SOC
LI plus CIZ (cyclophosphamide, indomethacin and zinc-multivitamins) was given as neoadjuvant therapy prior to standard of care (SOC).
干预措施: LI (Biological)
LI + CIZ + SOC
LI plus CIZ (cyclophosphamide, indomethacin and zinc-multivitamins) was given as neoadjuvant therapy prior to standard of care (SOC).
干预措施: Cyclophosphamide (Drug)
LI + CIZ + SOC
LI plus CIZ (cyclophosphamide, indomethacin and zinc-multivitamins) was given as neoadjuvant therapy prior to standard of care (SOC).
干预措施: Indomethacin (Drug)
LI + CIZ + SOC
LI plus CIZ (cyclophosphamide, indomethacin and zinc-multivitamins) was given as neoadjuvant therapy prior to standard of care (SOC).
干预措施: Zinc (Dietary Supplement)
LI + CIZ + SOC
LI plus CIZ (cyclophosphamide, indomethacin and zinc-multivitamins) was given as neoadjuvant therapy prior to standard of care (SOC).
干预措施: Surgery (Procedure)
LI + CIZ + SOC
LI plus CIZ (cyclophosphamide, indomethacin and zinc-multivitamins) was given as neoadjuvant therapy prior to standard of care (SOC).
干预措施: Cisplatin (Drug)
LI + CIZ + SOC
LI plus CIZ (cyclophosphamide, indomethacin and zinc-multivitamins) was given as neoadjuvant therapy prior to standard of care (SOC).
干预措施: Radiotherapy (Radiation)
Standard of Care (SOC) only
SOC for previously untreated SCCHN patients is currently surgery (with curative intent) followed by either radiotherapy or combined radiochemotherapy depending on the patient's risk status for recurrence as determined at surgery.
干预措施: Surgery (Procedure)
Standard of Care (SOC) only
SOC for previously untreated SCCHN patients is currently surgery (with curative intent) followed by either radiotherapy or combined radiochemotherapy depending on the patient's risk status for recurrence as determined at surgery.
干预措施: Cisplatin (Drug)
Standard of Care (SOC) only
SOC for previously untreated SCCHN patients is currently surgery (with curative intent) followed by either radiotherapy or combined radiochemotherapy depending on the patient's risk status for recurrence as determined at surgery.
干预措施: Radiotherapy (Radiation)
LI + SOC
LI was administered without CIZ to determine the contribution of CIZ to the effects of LI.
干预措施: LI (Biological)
LI + SOC
LI was administered without CIZ to determine the contribution of CIZ to the effects of LI.
干预措施: Surgery (Procedure)
LI + SOC
LI was administered without CIZ to determine the contribution of CIZ to the effects of LI.
干预措施: Cisplatin (Drug)
LI + SOC
LI was administered without CIZ to determine the contribution of CIZ to the effects of LI.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Overall Survival (OS)
时间窗: From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months.
OS was assessed using Kaplan-Meier life-table using a log rank test and confirmed further with tumor stage, tumor location, and geographic stratified log rank test. Both Stratified and unstratified log rank test are presented with the unstratified log rank test constituting the primary analysis. A two-sided p-value of 0.05 or less was considered statistically significant for comparing the two groups (i.e., Study comparator arms: LI+CIZ+SOC vs. SOC alone). Interim analyses were performed (by the iDMC) periodically throughout the study to assess safety, sample size and futility.
OS in Low Risk Subjects
时间窗: From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months.
OS was assessed using Kaplan-Meier life-table using a log rank test and confirmed further with tumor stage, tumor location, and geographic stratified log rank test. Both Stratified and unstratified log rank test are presented with the unstratified log rank test constituting the primary analysis. A two-sided p-value of 0.05 or less was considered statistically significant for comparing the two groups (i.e., Study comparator arms: LI+CIZ+SOC vs. SOC alone). Low-risk assessment and data analysis was never performed during the study and was done only after database lock.
次要结局
- PFS in Low Risk Subjects(From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months.)
- Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 2(Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 2)
- Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 36(Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 36)
- EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 2(Baseline [pre-randomization], Long Term Follow-up Month 2)
- EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 36(Baseline [pre-randomization], Long Term Follow-up Month 36)
- Local Regional Control (LRC)(From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months.)
- LRC in Low Risk Subjects(From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months.)
- Progression Free Survival (PFS)(From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months.)
- Statistical Comparisons of Time-to-event Outcomes (OS, LRC, PFS) Were Repeated for Varying Levels of Histopathology (HP) Markers in Low Risk Subjects(From the date of treatment assignment to event (LRC,PFS,OS) or the last follow-up date. Maximum follow-up was approximately 113 months.)