Phase I/II Trial of Erlotinib, Radiation Therapy, and Cisplatin in Patients With Complete Resected Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 53
- 试验地点
- 5
- 主要终点
- Determinate the maximum tolerated dose (PHASE I)
研究概览
简要总结
The purpose of the study is to determinate the free-progression interval in patients with surgically resected locally advanced squamous cell carcinoma of head and neck treated with the maximum tolerated dose of the combination of erlotinib, radiation therapy and cisplatin, previously established in a safety trial.
详细描述
Phase I:
3 cohorts of 3-6 patients, patients will received:
- Erlotinib 100-150 mg/day po for 7 weeks.
- Cisplatin 30-40 mg/m2 iv weekly for 7 weeks.
- Radiation therapy 63 Gy, five days a week, for 7 weeks. Cohort 1: 3 patients will be included in cohort 1.
If no DLT has been recorded in the first three patients during the 7-weeks treatment, the dose level of erlotinib will be escalated to 150 mg and enrollment of cohort 2 will be initiated.
If DLT has been recorded in one out of the first three patients during the during the 7-weeks treatment, then the first cohort will be expanded to 6 patients.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histological proof of epidermoid carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx, treated with surgical resection with curative intent.
- •Surgical resection must have taken place within 8 weeks prior to the patient's inclusion in the study.
- •In those patients having clinical regional lymph node involvement radical neck dissection is mandatory. However, radical neck dissection is not an inclusion criterion in patients staged as N
- •Age 18-70 years.
- •Anticipated life expectancy of ≥ 12 weeks.
- •Patients should have at least one of the following criteria:
- •Pathological T3-4 tumor stage, apart from T3N0 of the larynx with negative margins
- •Pathological N2-3 nodal stage.
- •Unfavorable pathological findings such as extranodal spread, positive resection margins, perineural and/or vascular involvement.
- •Written informed consent given by the patient.
- •Therapeutic compliance of the patient and geographical proximity to the hospital to facilitate appropriate follow-up.
- •No distant metastatic disease.
- •Adequate organ function according to the following criteria:
- •Adequate bone marrow reserve: ANC > 1,5 x 10(9) cells/L; Platelet count > 100 x 10(9) cells/L; Hemoglobin > 9 g/dL
- •Liver function: Bilirubin < 1.5 x ULN; Alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0 x ULN
- •Renal function: calculated creatinine clearance (CrCl) > 60ml/min or Creatinine (Cr) < 1.5 ULN of the reference laboratory.
- •Serum calcium and alkaline phosphatase must be normal.
- •Women of child bearing potential must have a negative pregnancy test within the 48h prior to the start of the treatment.
- •Patients of both genders at a fertile age must follow effective contraceptive measures.
- •Absence of symptomatic coronary artery disease or acute myocardial infarction within 6 months prior to study.
- •Patients capable of oral deglutition or requiring gastrostomy.
- •No problems of intestinal transit such as malabsorption syndrome, chronic inflammatory bowel disease and other diseases, which might impair drug absorption
排除标准
- •Histology other than squamous cell carcinoma.
- •Presence of macroscopic residual disease.
- •Previous treatment with chemotherapy or radiotherapy or EGFR-targeted agents.
- •Incomplete resection of the primary tumor or incomplete neck dissection.
- •Patients being diagnosed with any other malignant disease, excluding resected nonmelanoma skin cancer or resected uterine cervix carcinoma.
- •Pregnant or nursing women.
- •Active infection.
- •Concomitant severe illness (according to the opinion of the investigator) or whose estimated survival for this concomitant pathology is lower than that estimated for the neoplasm disease.
- •Uncontrolled psychiatric illness.
- •Inability to take oral medication, requiring intravenous feeding or prior surgical procedures affecting absorption or having active peptic ulcer.
- •Impossibility to appropriate follow-up.
- •Evidence of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding suggesting a condition that contraindicates the use of the study medication (erlotinib, cisplatin, radiotherapy), which might interfere with the analysis of the results or increase the risk of treatment complications.
- •Any known significant ophthalmologic abnormalities, including severe xerophthalmia, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratopathy or other abnormalities, which may increase the risk of corneal epithelial damage (the use of contact lenses during the study may increase the risk of corneal damage and its use is strongly discouraged. Those patients still using contact lenses will need a closer ophthalmologic follow-up.
- •Frequent vomiting or medical disorder impairing swallowing of drugs
研究组 & 干预措施
Erlotinib, radiotherapy.
There are three cohorts of patients in whom the dose of Erlotinib chlorhydrate(100 and 150 mg) and Cisplatin (30 and 40 mg / m2) will be increase, and the doses of Radiation therapy being fixed (63 Gy during 5 days a week during 7 weeks)
干预措施: Erlotinib chlorhydrate (Drug)
Erlotinib, radiotherapy.
There are three cohorts of patients in whom the dose of Erlotinib chlorhydrate(100 and 150 mg) and Cisplatin (30 and 40 mg / m2) will be increase, and the doses of Radiation therapy being fixed (63 Gy during 5 days a week during 7 weeks)
干预措施: Cisplatin (Drug)
Erlotinib, radiotherapy.
There are three cohorts of patients in whom the dose of Erlotinib chlorhydrate(100 and 150 mg) and Cisplatin (30 and 40 mg / m2) will be increase, and the doses of Radiation therapy being fixed (63 Gy during 5 days a week during 7 weeks)
干预措施: Radiation therapy (Procedure)
结局指标
主要结局
Determinate the maximum tolerated dose (PHASE I)
时间窗: 17/MAR/08
Progression free survival (PHASE II)
时间窗: 5 years
次要结局
- Overall survival and locoregional progression free survival (PHASE II)(5 years)
- DLT (PHASE I)(17/MAR/08)
研究者
Lola
Oncologist
Grupo de Investigación Clínica en Oncología Radioterapia