Multiinstitutional Open Label Randomized Phase II Study Comparing Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy as Firstline Treatment for Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-NHSCC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 70
- 试验地点
- 7
- 主要终点
- Compliance
研究概览
简要总结
BACKGROUND:
Concomitant radiotherapy and cisplatin (CDDP) based chemotherapy is the standard treatment for LA-NHSCC. This combined modality treatment is linked with considerable acute local and systemic toxicity.EGFR is overexpressed in 90-100% of the HNSCC cases and is considered an unfavourable prognostic marker. EGFR costitutive activation is linked with HNSCC pathogenesis.
Cetuximab is a monoclonal anti-EGFR antibody blocking the activation of the receptor and signal transduction. Cetuximab combined with radiotherapy is superior to radiotherapy only in the treatment of LA-HNSCC and is characterized by an acceptable toxicity profile.
RATIONALE:
A direct comparison between concomitant chemoradiotherapy with Cisplatin and the concomitant treatment with radiotherapy associated to cetuximab does not exist.
STUDY DESIGN:
Arm A: Radical radiotherapy (doses and volumes) concomitant with chemotherapy with Cisplatin (40 mg/mq/week) Arm B: Radical radiotherapy (doses and volumes) concomitant with therapy with the monoclonal antibody Cetuximab (400 mg/m2 ["loading dose"] and subsequently 250 mg /m2/week)
详细描述
PRIMARY OBJECTIVES:
Evaluation and comparison of the compliance of the two treatments;
SECONDARY OBJECTIVES:
Evaluation and comparison of the grade and incidence of acute toxicity; Evaluation and comparison of local control; Evaluation and comparison of event free survival (both local control and distant metastases); Evaluation and comparison of cause specific and overall survival.
INCLUSION/EXCLUSION CRITERIA
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 confirmed squamous cell carcinoma (with biopsy on the primary and / or lymph node metastases) of the oral cavity, oropharynx, hypopharynx, larynx supraglottix;
- •Locally advanced disease, defined by one of the following criteria: any T, N +, M0 (excluding T1, N1), T3-4, N0, M0;
- •Not cancer nasopharynx or paranasal sinuses or salivary glands;
- •General conditions and associated diseases which does not allow to perform chemotherapy or radiotherapy in a radical view;
- •No other surgical treatments, chemotherapy or radiotherapy for cancer of head and neck or elsewhere, except non-melanoma skin cancer or in situ cervical cancer and other solid tumors for which radical treatment has been completed > three years prior to enrollment in the study and for which the patient has remained continuously free of disease;
- •Accessibility to follow-up;
- •Signing of informed consent;
- •Interval between examinations of local staging and randomization, maximum 3 weeks
- •Interval between randomization and initiation of treatment, maximum 2 weeks
排除标准
- •Age <18 years
- •ECOG performance status > 0-1
- •Hemoglobin <9 g / dL
- •Counts of granulocytes, total <1.5 x 10 ^ 9 / L
- •Platelet count <100 x 10 ^ 9 / L
- •Bilirubin> 1.5 times upper limit of normal (ULN)
- •AST or ALT> 3 times ULN
- •Creatinine clearance > 50 mL/min
- •Mg > 0.5 mmol/L
- •Pregnancy or lactation
- •Presence of allergy to study drug or to the excipients used in their formulation
- •Peripheral neuropathy ≥ grade 2 (CTCAE v3.0)
- •Hearing loss / tinnitus ≥ grade 3 (CTCAE v3.0)
- •One of the following conditions:
- •Myocardial infarction within 12 months prior to randomization
- •Severe congestive heart failure
- •Unstable angina
- •Cardiomyopathy in act
- •Ventricular arrhythmia
- •uncontrolled hypertension
- •Severe psychotic disorders in act
- •Severe infection in act
- •Any other serious illness that could interfere with the administration of the therapy provided by the protocol
研究组 & 干预措施
cetuximab plus radiotherapy
Cetuximab given one week before radiotherapy (loading dose, 400 mg/m2) plus weekly (250 mg/m2), concomitant with radiotherapy (7O Gy on clinically involved sites).
干预措施: cetuximab (Drug)
cisplatin plus radiotherapy
CDDP 40 mg/mq in a single weekly 1-hour infusion concomitant to radiotherapy: (70 Gy to clinically involved sites)
干预措施: cisplatin (associated to radiotherapy) (Drug)
结局指标
主要结局
Compliance
时间窗: weekly during treatment
Evaluation and comparison of the compliance of the two treatments arms
次要结局
- event free survival(bimonthly for two years, every 6 months thereafter)
- acute toxicity(Weekly during treatment.)
- Local control(bimonthly for two years after treatment, every six months thereafter)
- cause specific survival(bimonthly after treatment for two years, then every 6 months)
- overall survival(bimonthly after treatment for two years, then every 6 months)
研究者
STEFANO M. MAGRINI, PROF
PROF
Azienda USL 4 Prato