Sorafenib and Cetuximab in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN):a Phase I B/II Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Phase 1 - Maximum Tolerated Dose (MTD) of Sorafenib Administered With Cetuximab (400 mg/m2 Loading Dose Followed by 250 mg/m2 Weekly)
研究概览
简要总结
In this Phase I B/II trial, we seek to determine the safety and efficacy of sorafenib with standard dose cetuximab in the treatment of patients with Recurrent and /or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN).
详细描述
This is a non-randomized phase I B/II trial enrolling 43 patients with recurrent and/or metastatic SCCHN who are not candidates for surgical salvage or definitive radiation. Subjects will receive Cetuximab and sorafenib until disease progression. Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib will be given 200 mg twice daily oral, continuous dosing to the 6 patients in cohort 1. If less than 3 patients experience dose limiting toxicities (DLT) at the 200mg BID dose, then 6 patients will be accrued at the 400mg BID dose level and toxicities will again be examined. Sorafenib will be given 400 mg twice daily oral, continuous dosing to the patients in cohort 2. One cycle equals 28 days. Tumor assessment will be performed every 8 weeks. Treatment continues until disease progression or unacceptable side effects.
Participating subjects will be asked to take part in an optional correlative study to provide previously archived diagnostic or therapeutic tumor samples obtained during the course of their routine medical care for their cancer of the head/neck. The optional tissue repository project is Duke University Health System (DUHS) Institutional Review Board (IRB) approved (eIRB # 11138 / "Tissue Acquisition Protocol for Analysis of Effects of Novel Chemotherapeutic Compounds). Subjects will be asked to sign a separate consent form to participate in the tissue collection study.
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
- •Histologically confirmed squamous cell carcinoma of the head and neck
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- •Age > 18 years old
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- •Adequate bone marrow, liver and renal function as assessed by the following:
- •Hemoglobin > 9.0 g/dl
- •Absolute neutrophil count (ANC) > 1,500/mm3
- •Platelet count > 100,000/mm3
- •Total bilirubin < 1.5 times upper limit of normal (ULN)
- •Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 2.5 times the ULN ( < 5 x ULN for patients with liver involvement)
- •Creatinine < 1.5 times ULN
- •Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- •Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
- •International normalized ratio (INR) < 1.5 or a Prothrombin Time / Partial thromboplastin time (PT/PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. - For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
排除标准
- •Patients must not be candidates for potentially curative complete surgical resection or definitive radiation. (Patients may have received prior chemotherapy as part of definitive chemoradiotherapy and/or for recurrent/metastatic disease)
- •Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- •Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
- •Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- •Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- •Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- •Active clinically serious infection > Common Terminology Criteria for Adverse events (CTCAE) Grade
- •Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- •Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 (symptomatic and requiring medical intervention) within 4 weeks of first dose of study drug.
- •Any other hemorrhage/bleeding event > CTCAE Grade 3 (bleeding requiring blood transfusion or intervention with endoscopy or surgery) within 4 weeks of first dose of study drug.
- •Serious non-healing wound, ulcer, or bone fracture.
- •Evidence or history of bleeding diathesis or coagulopathy Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
- •Use of St. John's Wort or rifampin (rifampicin).
- •Known or suspected allergy to sorafenib or any agent given in the this trial.
- •Any malabsorption problem.
- •Previous therapy with cetuximab for the treatment of recurrent and/or metastatic SCCHN. Previous therapy with cetuximab during definitive radiation therapy for locally advanced SCCHN is permitted so long as relapse of SCCHN occurred at least > 6 months (180 days) from the end of cetuximab therapy.
- •Previous therapy with sorafenib, sunitinib or another small molecule known to inhibit the vascular endothelial growth factor receptors.
研究组 & 干预措施
Cetuximab + sorafenib
Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib will be given at 200mg/m2 twice daily.
干预措施: Sorafenib (Drug)
Cetuximab + sorafenib
Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib will be given at 200mg/m2 twice daily.
干预措施: Cetuximab (Drug)
结局指标
主要结局
Phase 1 - Maximum Tolerated Dose (MTD) of Sorafenib Administered With Cetuximab (400 mg/m2 Loading Dose Followed by 250 mg/m2 Weekly)
时间窗: Cycle 1 (28 Days)
The MTD is based upon dose-limiting (DLTs) experienced during Cycle 1 of treatment. The MTD is the maximum dose level at which 0/6 or 1/6 patients experience DLT. Using Common Toxicity Criteria for Adverse EVents (CTCAE) version 3.0, DLTs are defined as any Grade 4 hematologic toxicity, or Grade 3 or 4 non-hematologic toxicity. A DLT will not be considered to have occurred in the case of a grade 3 or 4 allergic reaction due to cetuximab.
Tumor Control Rate
时间窗: 1 year
The proportion of patients for whom the best overall response is complete response (CR), partial response (PR) or stable disease (SD). A CR occurs when all lesions disappear; whereas, a PR is indicated when there is at least a 30% decrease in the sum of the longest diameters (LD) of the target lesion. A PD (progressive disease) occurs when there is at least a 20% increase in the sum of the LD relative to the smallest sum LD recorded since treatment is initiated. Disease is considered stable if there is no response and no PD. If follow-up assessments are not available, the best overall response is unevaluable.
次要结局
- Median Survival(5 years)
- Median Progression-Free Survival (PFS)(5 years)
- Phase 2 - Mean Change From Baseline in Quality of Life - Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N)(5 years)