Metabolomic and BH3 Profiling of Esophageal Cancers: Identification of Novel Assessment Methods of Treatment Response for Precision Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- BH3 Profiling of Pre-neoadjuvant Tumor Biopsy and Outcome of Pathological Complete Response After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Adenocarcinoma or Squamous Cell Carcinoma
研究概览
简要总结
Background:
The number of patients with esophageal cancer keeps rising. For many patients, a combination of surgery, chemotherapy, and radiation is necessary to completely treat the disease. Usually, patients receive chemotherapy and radiation at the same time followed by surgery to remove the part of the esophagus with the tumor (Neoadjuvant chemoradiotherapy (nCRT)). Researchers want to learn how to make this treatment more effective.
Objective:
To see if biopsies before treatment can show which patients will do the best with a combination of chemotherapy, radiation, and surgery.
Eligibility:
Adults at least 18 years old with esophageal adenocarcinoma or squamous cell carcinoma who should be treated with chemotherapy, radiation, and surgery.
Design:
Patients will undergo standard testing that is routine for all patients with this disease. These tests include:
Medical history
Physical exam with activity and nutritional assessment
Standard lab tests
Imaging studies including a computerized axial tomography (CAT) scan and positron-emission tomography (PET) scan
Breathing test into a machine to measure size and function of lungs.
Biopsy for a small sample of tumor is removed by esophagogastroduodenoscopy (EGD): A tube inserted into the mouth under anesthesia
Endoscopic ultrasound is performed in some but not all patients.
Patients will have nCRT at the clinic or with their local doctor.
In 6 -12 weeks after nCRT, patients will undergo surgery with:
- A robotically-assisted, minimally-invasive esophagectomy
- Or, a traditional, open approach.
After surgery, patients are usually in the hospital for 2 weeks and have a feeding tube for at least 2 weeks and potentially longer until they are eating enough to not lose weight.
Patients will return for follow-up visits with labs and CAT scans every 6 months for the first two years then every year afterwards.
详细描述
Background:
- The incidence of esophageal cancer continues to increase with an estimated 16,900 new cases and 15,700 deaths in 2016. Esophageal adenocarcinoma (EAC) is the dominant histology in the United States and accounts for the rising incidence; the incidence of esophageal squamous cell cancer (ESCC) remains stable.
- Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is now a standard approach for locally advanced, operable esophageal cancer.
- A survival advantage compared to surgery alone was demonstrated in the phase III Chemo
Radiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial.
- Patients who experience a pathological complete response (pCR) following neoadjuvant therapy are most likely to have long-term survival.
- Presently, accurate assessment of pathologic response requires esophagectomy. Positron-emissions tomography (fludeoxyglucose (FDG-PET)) and endoscopic evaluation with biopsies fail to detect cancer in a significant percentage of patients with residual disease following neoadjuvant therapy.
- Currently there are no validated tissue or serologic biomarkers which can be used to guide surgical management of esophageal cancer patients based on response to nCRT.
Primary Objective:
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Patients must have histologically confirmed esophageal adenocarcinoma (EAC) or esophageal squamous cell carcinoma (ESCC).
- •Disease should be deemed resectable by pre-operative computed tomography (CT) and/or positron-emission tomography (PET) scans and the patient should be operable based on surgeon assessment.
- •Patients willing to complete neoadjuvant chemoradiotherapy (nCRT) per standard of care followed by esophagectomy. Patients will be treated under protocol 04-C
- •18 years of age or older.
- •Able to understand and sign the Informed Consent Document.
- •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
- •Patients must have organ and marrow function that is not prohibitive of surgical resection as defined below:
- •leukocytes greater than or equal to 3,000/mcL
- •absolute neutrophil count greater than or equal to 1,500/mcL
- •platelets greater than or equal to 50,000/mcL
- •nCRT used in this study is potentially dangerous for developing human fetus. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration and 6 months post chemoradiotherapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- •Women must have a negative urine pregnancy test OR be post-menopausal for at least 2 years OR patient has had a hysterectomy
排除标准
- •Patients in which nCRT followed by surgery is not the appropriate management:
- •Early stage disease that requires local therapy without chemoradiotherapy (CRT).
- •Patients with metastatic disease.
- •Patients in which biopsy prior to starting nCRT is not obtainable.
- •Patients who previously received neoadjuvant chemotherapy
- •Concomitant medical problems in the opinion of physician that would place the patient at unacceptable risk for a major surgical procedure.
- •Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, heart failure, hepatic disease that prohibits administration of neoadjuvant therapy or surgery.
- •Women who are pregnant or breastfeeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
- •Patients with a diagnosis of another malignancy that is either active or in remission less than five years. Basal cell and squamous cell carcinoma of the skin are not contraindications to this protocol
研究组 & 干预措施
Neoadjuvant Chemoradiotherapy and esophagectomy
Standard of care neoadjuvant chemoradiotherapy (nCRT) and esophagectomy
干预措施: Chemoradiotherapy (Other)
Neoadjuvant Chemoradiotherapy and esophagectomy
Standard of care neoadjuvant chemoradiotherapy (nCRT) and esophagectomy
干预措施: Esophagectomy (Procedure)
结局指标
主要结局
BH3 Profiling of Pre-neoadjuvant Tumor Biopsy and Outcome of Pathological Complete Response After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Adenocarcinoma or Squamous Cell Carcinoma
时间窗: Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery
Two tumor samples and two normal esophagus samples will be obtained for BH3 profiling of pre-neoadjuvant tumor biopsy and outcome of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal adenocarcinoma or squamous cell carcinoma. Response will be defined by the Mandard Score. Major response with no viable tumor (Grade 1) and \<10% viable tumor (Grade 2) versus non major response of \>10% viable tumor (Grade 3-5) as assessed by final pathology. Grade 1-2 is better survival than Grade 3-5.
Metabolomic Signature in Tumor, Blood, or Urine and Outcome of Pathological Complete Response After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Adenocarcinoma or Squamous Cell Carcinoma
时间窗: After neoadjuvant therapy >4 weeks but prior to surgery
Specimens of normal esophagus, esophageal tumors, blood, or urine will be analyzed to determine specific signatures and outcome of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal adenocarcinoma or squamous cell carcinoma. Response will be defined by the Mandard Score. Major response with no viable tumor (Grade 1) and \<10% viable tumor (Grade 2) versus non major response of \>10% viable tumor (Grade 3-5) as assessed by final pathology. Grade 1-2 is better survival than Grade 3-5.
次要结局
- Overall Survival (OS) in Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Patients Undergoing Neoadjuvant Chemoradiotherapy (nCRT) and Esophagectomy(From treatment start date until date of death or date last known alive.)
- Metabolomic Profiles and B-cell Lymphoma (Bcl-2) Homology Domain-3 (BH-3) Profiling in Resectable Esophageal Adenocarcinomas (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Treated With Neoadjuvant Chemoradiotherapy (nCRT)(Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery)
- Tumor Protein 53 (p53) Mutational Status and the Metabolomic Profiles(Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery)
- Metabolomic Signatures or BH3 Profiling in Tumor, Blood, or Urine of Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) With Major Responses (Mandard Score of 1 and 2) Versus Minimal Response (Mandard Score 3-5)(Pre-neoadjuvant therapy within 4 weeks, and after neoadjuvant therapy >4 weeks but prior to surgery)
- Disease-free Survival in Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC) Patients Undergoing Neoadjuvant Chemoradiotherapy (nCRT) and Esophagectomy(From the time of esophagectomy until development of metastatic disease or death, whichever comes first)
研究者
Caryn Steakley, R.N.
Deputy Clinical Director
National Institutes of Health Clinical Center (CC)