A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma

National Cancer Institute (NCI)634 个研究点分布在 1 个国家目标入组 203 人开始时间: 2011年2月14日最近更新: 2026年6月2日

适应症

干预措施

试验速览

阶段: 3 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 203
试验地点: 634
主要终点: Disease-free Survival (DFS)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer.

详细描述

PRIMARY OBJECTIVES:

l. To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing esophageal adenocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate if the addition of trastuzumab to trimodality treatment increases the pathologic complete response rate and overall survival for patients with HER2-overexpressing esophageal adenocarcinoma.

II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma.

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

•Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction; the cancer may involve the stomach up to 5 cm
•Endoscopy with biopsy
•PRIOR TO STEP 1 REGISTRATION BUT WITHIN 56 DAYS PRIOR TO STEP 2 REGISTRATION
•Intent to submit tissue for central HER2 testing
•Stage T1N1-2, T2-3N0-2, according to the American Joint Committee on Cancer (AJCC) 7th edition staging, based on the following minimum diagnostic work-up:
•Chest/abdominal/pelvic computed tomography (CT) or whole-body positron emission tomography (PET)/CT (NOTE: if CT is performed at this time point, whole-body PET/CT will be required prior to step 2 registration; PET/CT of skull base to mid-thigh is acceptable) (NOTE: if adenopathy is noted on CT or whole-body PET/CT scan, an endoscopic ultrasound is not required prior to STEP 2 registration as long as adequate tissue has been obtained for central HER2 testing)
•Patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be =< 2 cm
•Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula
•Zubrod performance status 0-2
•Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
•Platelets >= 100,000 cells/mm^3
•Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)
•Creatinine =< 2 times upper limit of normal
•Bilirubin =< 1.5 times upper limit of normal
•Aspartate aminotransferase (AST) =< 3.0 times upper limit of normal
•For women of childbearing potential, a negative serum or urine pregnancy test
•Patients must sign a study-specific informed consent prior to study entry
•CONDITIONS FOR PATIENT ELIGIBILITY PRIOR TO STEP 2 REGISTRATION (HER2-POSITIVE PATIENTS ONLY)
•HER2 expressing adenocarcinoma of the esophagus centrally
•Surgical consultation to confirm that patient will be able to undergo curative resection after completion of chemoradiation within 56 days prior to step 2 registration
•Radiation oncology consultation to confirm that disease can be encompassed in a radiotherapy field within 56 days prior to step 2 registration
•Consultation with a medical oncologist within 56 days prior to step 2 registration
•Stage T1N1-2, T2-3N0-2, according to the AJCC 7th edition staging, based upon the following minimum diagnostic work-up:
•History/physical examination, with documentation of the patient's weight, within 14 days prior to step 2 registration
•Whole-body PET/CT scan within 56 days prior to step 2 registration (if only CT performed prior to step 1 registration)
•Endoscopic ultrasound within 56 days prior to step 2 registration, unless the patient is found to have adenopathy per CT or whole-body PET/CT scan
•Electrocardiogram (EKG) within 56 days prior to step 2 registration
•Serum creatinine =< 2 x the upper limit or normal within 14 days prior to step 2 registration
•Zubrod performance status 0-2 within 14 days prior to step 2 registration
•For women of childbearing potential, a negative serum pregnancy test within 14 days prior to step 2 registration
•Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by cardiac echocardiogram (echo) or multi gated acquisition (MUGA) scan within 56 days prior to step 2 registration
•Women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab

排除标准

•Patients with cervical esophageal carcinoma
•Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm)
•Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable
•Prior radiation therapy for esophageal cancer or prior chest radiotherapy
•Prior anthracycline or taxane
•Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi
•Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible)
•Medical contraindications to esophagectomy
•Prior therapy with any agent targeting the HER2 pathway or human epidermal growth factor receptor 1 (HER1) (epidermal growth factor receptor [EGFR]) pathway
•Prior therapy with trastuzumab
•Prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody
•Previous history of congestive heart failure
•Severe, active comorbidity, defined as follows:
•Unstable angina in the last 6 months
•Transmural myocardial infarction within the last 6 months
•Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
•Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients
•Pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

研究组 & 干预措施

Arm I (radiotherapy, chemotherapy, trastuzumab)

Experimental

Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and 57 and paclitaxel intravenously IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over 30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease progression or unacceptable toxicity.

干预措施: Paclitaxel (Drug)

Arm I (radiotherapy, chemotherapy, trastuzumab)

Experimental

干预措施: Therapeutic Conventional Surgery (Procedure)