A Multi-Center, Open-Label, Multiple Administration, Rising Dose Study of the Safety, Tolerability, and Efficacy of IL-12 Gene Medicine in Patients With Unresectable or Recurrent/Refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 4
- 主要终点
- Maximum Tolerated Dose (MTD) [Phase I]
研究概览
简要总结
Participant with squamous cell cancer of head and neck are invited to participate in this study. In this study the investigators will be Inserting the gene for interleukin-12 into a person's cancer cells with the anticipation to make the body build an immune response to kill more tumor cells.
详细描述
This is a Phase I/II trial to study the effectiveness of gene therapy in treating patients who have unresectable, recurrent, or refractory head and neck cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Females must be non-pregnant and non-lactating and either surgically sterile (via hysterectomy or bilateral tubal ligation), at least one year post-menopausal, or using acceptable methods of contraception for the duration of the study.
- •Male subjects must be surgically sterile or using an acceptable method of contraception for the duration of the study.
- •Disease: biopsy-proven unresectable or recurrent/refractory squamoussell_eareinoma_of_the:head-and-neck-(usualLy -Stage-Di-or-IV) -
- •Tumor accessible to direct injection
- •Karnofsky performance of at least 70%
- •Life expectancy of at least three months
- •Able to give written informed consent
排除标准
- •Infection (concurrent or within previous 2 weeks)
- •Active or clinically-relevant viral illnesses.
- •Use of corticosteroids, high-dose non-steroidal antiinflammatory, or immunosuppressive drugs
- •Chemotherapy, radiotherapy or immunotherapy within 28 days of study entry or during the course of study
- •Respiratory disease sufficient to influence oxygenation of arterial blood
- •Active liver disease with transaminases >3 times the upper limit of normal
- •Previous history of liver disease
- •NYHA Class EU or greater heart failure
- •Serum creatinine of greater than 1.5 times the upper limit of normal
- •Polymorphonuclear neutrophilic leukocyte count <3,000/mm3
- •Platelet count <50,000/mm 3
- •Tumor involving major blood vessels or obstructing the airway
- •Previous treatment with viral-based gene therapy, recombinant DNA products, or bacterial plasmids
- •Use of an investigational drug within 30 days of screening
- •Other malignancies requiring treatment during the study
- •Scheduled surgical resection
- •History of autoimmune disease, including rheumatic disease, Crohn's disease, etc. ,
- •Known allergy to polyvinylpyrrofidone (PVP) or related products
- •History of psychiatric disabilities or seizures.
研究组 & 干预措施
IL-12 Injection 3mg/ml [Phase I]
The dosing schedule will consist of eight injections 3 mg/ml of formulated plasmid over a seven week period.
干预措施: IL-12 (Biological)
IL-12 Injection MTD [Phase II]
The dosing schedule will consist of eight injections over a seven week period of formulated plasmid at the MTD established in the phase I portion.
干预措施: IL-12 (Biological)
IL-12 Injection 6mg/ml [Phase I]
The dosing schedule will consist of eight injections 6mg/ml of formulated plasmid over a seven week period.
干预措施: IL-12 (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD) [Phase I]
时间窗: Assessed during therapy up to 7 weeks.
The MTD of IL-12 gene medicine is determined by the number of participants who experience a dose limiting toxicity (DLT). The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed in the two dose levels planned then evaluation of a third escalation will be considered. If the MTD is not reached, the dose selected for use in the phase II portion will be defined as the maximum volume that can be reasonably and safely injected into the tumor.
Dose Limiting Toxicity (DLT) [Phase I]
时间窗: Assessed during therapy up to 7 weeks.
A DLT was defined as grade 4 hematologic toxicity greater than 5 days duration or grade 3 or higher non-hematologic toxicity based on NCI common toxicity criteria (CTCAEv2).
Grade 3-4 Toxicity Rate [Phase II]
时间窗: Assessed until last scheduled on-study visit up to visit 12/day 112.
All Grade 3-4 events based on CTCAEv2 as reported on case report forms.
次要结局
- Response [Phase II](Measurement by CT occurs up to visit 12/day 112.)
- Overall Survival (OS) [Phase II](Measurement by CT occurs up to the earliest of progression, death or 4 months after enrollment of last patient.)
- Time to Progressive Disease (TTP) [Phase III](Measurement by CT occurs up to the earliest of progression, death or 4 months after enrollment of last patient.)
研究者
Robert I. Haddad, MD
Haddad, Robert MD
Dana-Farber Cancer Institute