A Phase II Study of Albumin Bound-Paclitaxel (AbraxaneTM) for Treatment of Recurrent or Metastatic Head and Neck Cancer With the Addition of Cetuximab (Erbitux) (IMC-225) on Disease Progression
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Overall Response Rate (Complete and Partial Response)
研究概览
简要总结
Primary Objective: To assess the overall response rate (complete and partial response) to Abraxane in patients with recurrent or metastatic head and neck cancer with the addition of Cetuximab on disease progression.
Approximately 40,000 new cases of head and neck cancer are diagnosed annually in the United States (Jemal et al, 2003), and over 30% of these patients are expected to die of their malignancy. Squamous cell carcinoma accounts for more than 90% of head and neck cancer cases. Although metastatic disease at the time of diagnosis is rather uncommon, and despite aggressive use of up-front concurrent radiation and cisplatin-based chemotherapy, approximately 20% of the patients will develop metastases. Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) have a poor prognosis
A subsequent randomized study conducted by ECOG (E1393) compared high-dose paclitaxel (200 mg/m2) as a 24-hour infusion plus cisplatin 75 mg/m2 with G-CSF support, to low dose paclitaxel (135 mg/m2) as a 24-hour infusion, plus cisplatin 75 mg/m2 (Forastiere et al, 2001). Patients with newly diagnosed metastatic or recurrent squamous cell carcinoma of the head and neck, excluding nasopharyngeal primaries were eligible. No prior treatment for recurrent/metastatic disease was allowed, but patients could have received chemotherapy as a part of the initial curative therapy that should have been completed 6 months prior to study.
No statistically significant difference could be demonstrated either in response rates or survival between the two arms (Murphy et al, 2001). This study, however, indicated that paclitaxel, a member of the taxane class of anti-tumor agent, is active in head and neck cancer.
New agents to treat head and neck cancer need to be investigated. Abraxane, an albumin-bound formulation of paclitaxel has shown significant single-agent activity in breast cancer and in head and neck cancer. Recently, Abraxane has approved for use in metastatic breast cancer. Given previous randomized phase III trials indicated single agent chemotherapy fared as well as combination chemotherapy regimen in terms of overall survival, this novel formulation should be actively investigated in head and neck cancer.
详细描述
OBJECTIVES
Primary Objective: To assess the overall response rate (complete and partial response) to Abraxane in patients with recurrent or metastatic head and neck cancer with the addition of Cetuximab on disease progression.
Secondary Objectives: 1. To assess the frequency and severity of toxicities associated with this treatment. 2. To evaluate overall survival and progression-free survival in patients with recurrent or metastatic head and neck cancer treated with single agent Abraxane. 3.To assess whether the addition of Cetuximab will re-sensitize head and neck cancer to Abraxane after progression on single agent Abraxane.
BACKGROUND AND RATIONALE
Approximately 40,000 new cases of head and neck cancer are diagnosed annually in the United States (Jemal et al, 2003), and over 30% of these patients are expected to die of their malignancy. Squamous cell carcinoma accounts for more than 90% of head and neck cancer cases. Although metastatic disease at the time of diagnosis is rather uncommon, and despite aggressive use of up-front concurrent radiation and cisplatin-based chemotherapy, approximately 20% of the patients will develop metastases. Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) have a poor prognosis. Their median survival is about 6-8 months. Selected patients with locally recurrent disease can be treated with a curative intent with locoregional therapies, such as salvage surgery or radiation (De Crevoisier et al, 1998); however the majority of these patients die of their disease. Despite high response rates, combination chemotherapy has not been shown to produce a survival benefit compared to single agents in randomized trials in patients with recurrent/metastatic head and neck cancer (Forastiere et al, 1992; Jacobs et al, 1992; Clavel et al, 1994). A phase III randomized study conducted by Southwest Oncology Group (SWOG) compared cisplatin-based combination chemotherapy to single agent methotrexate (Forastiere et al, 1992). The objective response rates were 32%, 21%, and 10%, for cisplatin/5-Fluorouracil (5-FU), carboplatin/5-FU, and single methotrexate, respectively, but the median overall survival was not statistically different between the three arms (ranged between 5 to 6.6 months). Moreover, toxicity was increased with combination therapy, especially with the cisplatin-based regimen. Another randomized study conducted in the US demonstrated a significantly higher response rate of 32% for the combination of cisplatin and 5-FU versus 17% and 13% for single agent cisplatin and 5-FU, respectively (Jacobs et al, 1992). However, the median survival of all patients was 5.7 months, with no difference between the three arms. Hematologic toxicity was increased in the combination arm.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must have histologically or cytologically confirmed carcinoma of the head and neck region. Primary tumor sites include: lip and oral cavity, major salivary glands, pharynx (oropharynx, nasopharynx, hypopharynx), or larynx (supraglottis, glottis, subglottis), nasal cavity and paranasal sinuses, and thyroid
- •Patients must have metastatic or locally recurrent squamous cell carcinoma of the head and neck. Patients with locoregional disease must be considered incurable by means of locoregional therapy.
- •All sites of disease must be assessed and designated as measurable or non-measurable disease as documented by CT, MRI, X-ray physical exam or nuclear exam. All measurable and non-measurable disease must be assessed within 28 days prior to registration.
- •Patients may have prior chemotherapy for recurrent/metastatic disease. However, all chemotherapy must be completed at least 21 days prior to scheduled start of Abraxane.
- •Patients must have adequate bone marrow reserve as documented by absolute neutrophil count (ANC) > 1,500 μl and platelets > 100,000/ μl obtained within 14 days prior to registration.
- •Patients must have adequate hepatic as documented by serum bilirubin < 1.5 x the institutional upper limit of normal. These tests must be obtained within 14 days prior to registration.
- •All patients must be 18 years of age or older
- •Patients must have a Zubrod performance of 0-3
排除标准
- •Patients must not have prior therapy with Abraxane
- •Patients with any evidence of active or uncontrolled infection, recent myocardial infection, unstable angina, or life-threatening arrhythmia are not eligible.
- •Patients with baseline grade 3 peripheral neuropathy are not eligible.
- •Patients with known brain metastasis are not eligible. However, brain-imaging studies are not required for eligibility if the patient has no neurological signs or symptoms. If brain-imaging studies are performed, they must be negative for disease.
研究组 & 干预措施
Abraxane plus Cetuximab
Drug: Abraxane-260 mg/m2 IV over 30 minutes every 3 weeks. Drug: Cetuximab will be added to Abraxane if there is documented progression on single agent Abraxane. First dose: 400 mg/m2 IV over 120 minutes. Weekly: 250 mg/m2 IV over 60 minutes Days 8 and 15 of cycle 1 and days 1, 8, 15 of all subsequent cycles.
干预措施: Abraxane (Drug)
Abraxane plus Cetuximab
Drug: Abraxane-260 mg/m2 IV over 30 minutes every 3 weeks. Drug: Cetuximab will be added to Abraxane if there is documented progression on single agent Abraxane. First dose: 400 mg/m2 IV over 120 minutes. Weekly: 250 mg/m2 IV over 60 minutes Days 8 and 15 of cycle 1 and days 1, 8, 15 of all subsequent cycles.
干预措施: Cetuximab (Drug)
结局指标
主要结局
Overall Response Rate (Complete and Partial Response)
时间窗: 3 years
To assess the overall response rate (complete and partial response) to Abraxane in patients with recurrent or metastatic head and neck cancer.
次要结局
- Overall Survival and Progression-free Survival in Patients(3 years)
- Frequency and Severity of Toxicities(3 years)
研究者
Sai-Hong Ignatius Ou
HS Clinical Professor
University of California, Irvine