An Exploratory Study to Assess the Modulation of Biomarkers in Patients With Squamous Cell Carcinomas of the Head and Neck Randomized to Receive Preoperative Treatment With Cetuximab and/or IMC-A12, an Anti-insulin-like Growth Factor-1 Receptor Monoclonal Antibody
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- AKT Modulation
研究概览
简要总结
The goal of this clinical research study is to give cetuximab and/or IMC-A12 before surgery for squamous cell carcinoma of the head and neck, in order to learn if these study drugs may cause changes in biomarkers. Biomarkers are chemical "markers" in the blood and/or tissue that may be related to a reaction to study treatment.
The safety of the study treatments will also be studied.
详细描述
The Study Drugs Cetuximab and IMC-A12 are both designed to block proteins that are thought to cause cancer cells to grow. This may help to slow the growth of tumors.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 3 groups. There is an equal chance of being assigned to any group.
- Group 1 will receive cetuximab alone.
- Group 2 will receive IMC-A12 alone.
- Group 3 will receive cetuximab and IMC-A12 in combination.
If you are assigned to group 2 or 3 you will have a hearing test within 90 days before starting treatment with the study drug.
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
- •Histologically or cytologically-confirmed diagnosis of squamous cell carcinoma of the head and neck (excluding carcinomas of the nasopharynx types II and III according to the World Health Organization criteria), for whom surgical resection of the tumor is planned as part of the treatment. Patients with skin squamous cell carcinomas of the head and neck region will also be included in this study.
- •There is availability of a baseline, paraffin-embedded, tumor specimen for biomarker evaluation. No anti-neoplastic treatment is allowed between the time from obtaining the baseline tumor specimen and randomization. If a baseline tumor specimen is not available, a biopsy of the tumor will be performed prior to randomization.
- •Prior treatment with biological agents targeted to the epidermal growth factor receptor is allowed, provided the time from last exposure to this treatment was >/= 6 months.
- •The patient has a fasting serum glucose < 130 mg/dL and HbA1C < 7.0%. Patients with a history of diabetes mellitus are allowed to participate, provided that they are on a stable dietary or therapeutic regimen for this condition.
- •The patient has adequate renal function, defined by serum creatinine </= 1.5 x the institutional upper limit of normal (ULN), or creatinine clearance >/=60 mL/min for patients with creatinine levels above the ULN.
- •Because the teratogenicity of cetuximab and IMC-A12 is not known, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
- •The patient is age >/= 18 years.
- •The patient or the patient's legally authorized representative has the ability to understand and the willingness to sign a written informed consent document.
- •ECOG performance status of 0-2.
排除标准
- •Patients receiving any other agent (investigational or not) with potential anti-neoplastic activity within 3 weeks prior to obtaining the baseline tumor specimen for biomarker evaluation.
- •Patients receiving concomitant radiation.
- •Prior treatment with an agent targeted at the insulin-like growth factor-1 receptor.
- •History of allergic reactions attributed to compounds of chemical and biological composition similar to those of cetuximab or IMC-A
- •Pregnant patients, or patients who are breast feeding (patients who have a positive pregnancy test within the first 30 days before the first dose of treatment are excluded).
- •Patients with uncontrolled illnesses which, in the opinion of the investigator, could be aggravated by the administration of the study drug(s).
研究组 & 干预措施
Group 1: Cetuximab
Cetuximab: 400 mg/m2 i.v. over 120 minutes on week 1, and 250 mg/m2 on week 2 and 3 i.v. over 60 minutes
干预措施: Cetuximab (Drug)
Group 1: Cetuximab
Cetuximab: 400 mg/m2 i.v. over 120 minutes on week 1, and 250 mg/m2 on week 2 and 3 i.v. over 60 minutes
干预措施: Surgical tumor resection (Procedure)
Group 2: IMC-A12
IMC-A12: 6 mg/kg/week i.v. over 1 hour on weeks 1 and 2 and 3.
干预措施: IMC-A12 (Drug)
Group 2: IMC-A12
IMC-A12: 6 mg/kg/week i.v. over 1 hour on weeks 1 and 2 and 3.
干预措施: Surgical tumor resection (Procedure)
Group 3: Cetuximab + IMC-A12
Cetuximab: 400 mg/m2 i.v. over 120 minutes on week 1, and 250 mg/m2 on week 2 and 3 i.v. over 60 minutes.
IMC-A12: 6 mg/kg/week i.v. over 1 hour on weeks 1 and 2 and 3.
干预措施: Cetuximab (Drug)
Group 3: Cetuximab + IMC-A12
Cetuximab: 400 mg/m2 i.v. over 120 minutes on week 1, and 250 mg/m2 on week 2 and 3 i.v. over 60 minutes.
IMC-A12: 6 mg/kg/week i.v. over 1 hour on weeks 1 and 2 and 3.
干预措施: IMC-A12 (Drug)
Group 3: Cetuximab + IMC-A12
Cetuximab: 400 mg/m2 i.v. over 120 minutes on week 1, and 250 mg/m2 on week 2 and 3 i.v. over 60 minutes.
IMC-A12: 6 mg/kg/week i.v. over 1 hour on weeks 1 and 2 and 3.
干预措施: Surgical tumor resection (Procedure)
结局指标
主要结局
AKT Modulation
时间窗: Biopsy at baseline and surgery (surgery should be within 10 days of last treatment)
An IHC scoring system used to quantify phospho-Akt levels based on staining intensity x extension. Staining intensity graded as undetectable (0), weak (1), medium (2), or strong (3). Staining extension graded as percentage of positive cells per high power field at x20 magnification. Final score will therefore range from 0 to 300. Modulation of phospho-Akt (difference in IHC score between the surgical specimen and the baseline biopsy) and other biomarkers compared between any two of the three treatment arms with the use of the Wilcoxon rank sum test. Type I error of alpha=0.05 (two-sided test) used. Correlation between biomarkers and molecular response or toxicity performed in an exploratory fashion.
次要结局
- Number of Participants With Objective Response(up to 4 months post treatment start)