A Pilot Trial Targeting mTOR as a Novel Mechanism-Based Neoadjuvant Therapy for Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Percent (%) Change in Levels of pS6, pAKt473, and Ki-67
研究概览
简要总结
Background:
- Advanced-stage head and neck cancer (head and neck squamous cell carcinoma [HNSCC]) has moderately successful treatment outcomes, usually involving surgery as part of the standard treatment. Researchers are investigating the use of the drug rapamycin to prevent tumor growth in HNSCC, and are interested in using it to treat individuals with HNSCC that has not been treated previously with other drugs, radiation, or surgery.
Objectives:
- To evaluate the usefulness of rapamycin in decreasing tumor size prior to surgery for head and neck squamous cell carcinoma.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with advanced head and neck squamous cell carcinoma that has not yet been treated.
Design:
- Participants will be screened with a physical examination, medical history, blood tests, and imaging studies.
- Approximately 1 month before scheduled surgery, participants will begin to receive rapamycin. Participants will take rapamycin once daily for 21 days, followed by a 7-day period without the drug.
- During the 21-day rapamycin treatment, participants will have weekly study visits to provide blood and urine samples and have possible tumor biopsies and imaging studies such as x-rays or tumor photographs. Participants will have additional study visits for tests 1 day and 1 week after the end of rapamycin treatment, followed by HNSCC surgery.
- Participants will have a final visit to provide blood samples 30 days after surgery.
- Participants medical records will be reviewed 1 year after surgery; however, participants will not need to have further study visits at this time.
详细描述
BACKGROUND:
- The five-year survival rate for head and neck squamous cell carcinoma (HNSCC) has remained at approximately 50% for more than three decades.
- In HNSCC, the AKT-mTOR-pS6 pathway is aberrantly activated and promotes tumorigenesis and metastasis.
- Rapamycin is the most extensively studied mTOR inhibitor for which therapeutic daily oral dose and schedule, pharmacologic levels in blood, and safety have been established.
- Inhibition of mTOR by rapamycin causes the rapid apoptotic death of HNSCC tumor xenografts and decreases the tumor burden and prolongs the survival of mice harboring early and advanced oral and skin SCC lesions in a variety of experimental cancer models.
- Preliminary evidence suggests that mTOR inhibitors cause tumor shrinkage and improved tumor margins in HNSCC patients.
OBJECTIVES:
-
The primary objectives are to evaluate the following for patients with HNSCC given rapamycin as neoadjuvant treatment prior to surgery or chemoradiation:
-
Whether therapeutic activities of rapamycin lead to inhibition of mTOR complexes, mTORC1 and mTORC2, as assessed by the change in levels of pS6 and pAkt473 measured by immunohistochemistry (IHC) in tumor samples and by Western blotting in peripheral blood mononuclear cells (PBMCs) and reduce tumor cell proliferation, as judged by IHC for Ki-67 in tumor samples.
-
Antitumor activity in terms of objective response.
-
Secondary objectives include safety evaluation of rapamycin therapy, exploratory studies of possible effects of rapamycin on tumor size, dynamic CT perfusion, and FDG-PET; and evaluation of tumor proliferation, apoptosis, microvessel density, and molecular changes associated with these effects. Survival status, recurrence of disease, metastases, and adverse events/serious adverse events, including complications of wound healing, which are related to rapamycin therapy will also be assessed for 360 days after surgery or chemoradiation through medical record review.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 80 Years（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
Sirolimus
Subjects will be treated with sirolimus 21 days
干预措施: Sirolimus (Drug)
结局指标
主要结局
Percent (%) Change in Levels of pS6, pAKt473, and Ki-67
时间窗: 21 days post treatment with rapamycin
Percent (%) Change in Clinical and Laboratory Evaluations for Safety
时间窗: Percent (%) change from Pre to Post treatement (~21 days)
Percent (%) Changes in Tumor Size, Blood Flow, and Standardized Uptake Value
时间窗: 21 days post treatment with rapamycin
次要结局
未报告次要终点