Phase I Study of Bortezomib and Cetuximab Without or With Cisplatin in Combination With Radiation Therapy for Advanced Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Evaluate feasibility/toxicities of combining proteasome inhibitor bortezomib with cetuximab without/with cisplatin concurrent with radiation for therapy of Pts with advanced SCCHN, and identify MTD for bortezomib for further clinical phase 2 dev...
研究概览
简要总结
Background:
Bortezomib acts on molecules in head and neck cancer cells that are important for the cells growth and survival. The drug may help make the cancer more sensitive to radiation and other chemotherapy drugs.
Cetuximab is a monoclonal antibody that has increased the effectiveness of radiation treatment in patients with head and neck cancer in clinical trials.
Cisplatin has shrunk head and neck cancers and improved treatment response and survival when combined with radiation treatment.
Objectives:
To determine the highest safe dose of bortezomib when combined with cetuximab without or with cisplatin and with radiation in patients with advanced head and neck cancer.
To examine the benefits and side effects of these drug combinations with radiation in patients with advanced head and neck cancer.
Eligibility:
Patients 18 years of age and older with advanced Stage IV head and neck cancer who have not previously had neck radiation.
Design:
Patients will be assigned sequentially to one of two treatment groups: Group A receives bortezomib and cetuximab beginning the week before, and for the duration of, radiation therapy; Group B receives bortezomib, cetuximab and cisplatin beginning the week before, and for the duration of, radiation therapy.
- Cetuximab is given as a 2-hour infusion through a vein (intravenously, IV) for the first dose and then over 1 hour for subsequent weekly doses.
- Bortezomib is given as an injection into a vein over about 5 seconds, twice a week for 2 weeks, followed by a 1-week rest for a total of three 3-week treatment cycles during radiation.
- Cisplatin is given in once a week as a 1-hour IV infusion
- Radiation therapy is given 5 days a week for 7 to 8 weeks.
Post-treatment follow-up:
- Until 2 weeks after treatment ends, patients are followed once a week including a physical examination, review of treatment side effects, and blood tests.
- For 2 months after treatment ends, patients may need to return to the hospital for medical evaluation and supportive care, depending on their condition.
- 8-weeks after treatment ends, patients return for evaluation with a history and physical examination; blood tests; ear, nose and throat evaluation and endoscopy; CT or MRI scan, or both, of the neck and chest; and, if indicated, a PET scan....
详细描述
Background:
- Advanced squamous cell carcinoma involving the head and neck (SCCHN) has a mortality exceeding 50 percent and significant impact on function and quality of life.
- Treatment of locally advanced SCCHN with anti-Epidermal Growth Factor Receptor (EGFR) antibody cetuximab (Erbitux or C225) or DNA damaging agent cisplatin concurrent with radiation therapy (RT) have shown improvements in response, survival, and organ preservation, of approximately10-20 percent over RT alone. The combination of cetuximab, cisplatin and RT is currently under investigation as the next standard for concurrent chemo-RT for patients with SCCHN.
- Cetuximab inhibits EGFR, which is overexpressed by approximately 90 percent of SCCHN and is associated with decreased patient survival. EGFR contributes to activation of the Mitogen Activated Protein Kinase (MAPK) and Signal Transduction and Activating Transcription Factor (STAT3) pathways, which promote induction of genes involved in cell proliferation and survival.
- Recently, the Nuclear Factor-kappaB (NF-kB) pathway has been shown to be an independent pathway important for altered expression of prosurvival genes, the malignant phenotype, and prognosis.
- Proteasome inhibitor bortezomib (Velcade, PS-341) can inhibit NF-kB and target genes, as well as increase expression of tumor suppressor genes such as p53 in SCCHN. Bortezomib in combination with RT, cetuximab or cisplatin induces greater cytotoxic effects in cancer cells than these treatments individually in preclinical studies.
- In this phase I trial we will determine the feasibility of administering bortezomib concurrently with cetuximab and RT, and cetuximab, cisplatin and RT. We hypothesize that bortezomib can be given with these combinations with an acceptable toxicity profile and a maximum tolerated dose (MTD) that demonstrates clinical activity and effects on NF-kB, MAPK and STAT3 pathway signaling and apoptosis in SCCHN.
Specific Objectives:
Primary Objectives
-To evaluate the feasibility and toxicities of combining the proteasome inhibitor bortezomib with cetuximab, or cetuximab and cisplatin concurrent with radiation for therapy of patients with advanced squamous cell carcinoma of the head and neck (SCCHN), and to identify the MTD for bortezomib for further clinical phase 2 development.
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 90 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
结局指标
主要结局
Evaluate feasibility/toxicities of combining proteasome inhibitor bortezomib with cetuximab without/with cisplatin concurrent with radiation for therapy of Pts with advanced SCCHN, and identify MTD for bortezomib for further clinical phase 2 dev...
次要结局
- 1) Evaluate objective response rate, progression-free survival/overall survival with the above regimen. 2) Determine effects of bortezomib with cetuximab or with cetuximab/ cisplatin to inhibit activation of NF-kB, EGFR, MAPK, and STAT3 signal p...