Trimodality Management of T1b Esophageal Cancers
Trimodality Management of T1b Esophageal Cancers
The goal of this clinical research study is to learn if giving chemotherapy and radiation
 therapy before surgery for early-stage esophageal cancer can help to control the disease and
 if so, for how long. The safety of this treatment will also be studied.
The Study Treatment:

 5-fluorouracil and docetaxel are designed to stop the growth of cancer cells, which may cause
 the cells to die. Docetaxel may also damage blood vessels in tumor tissue.

 The radiation therapy in this study will be either intensity modulated radiation therapy
 (IMRT), which is a form of photon-based radiation therapy, or proton beam therapy (PBT). This
 will be up to your doctor. Both IMRT and PBT are designed to give radiation to the tumor area
 and limiting radiation exposure to nearby organs such as the lungs, heart, and spinal cord.

 The surgery in this study removes part of the esophagus and nearby lymph nodes. The type of
 surgery will be the doctor's decision based on the location of the tumor in the esophagus. It
 will either be laparoscopic surgery (a minimally invasive procedure through small holes made
 in the abdomen) or open surgery (through the chest wall).

 Study Treatment Administration:

 If you are found to be eligible to take part in this study, you will receive radiation
 therapy and chemotherapy on the following schedule for up to 5 1/2 weeks. If there are
 holidays on the scheduled treatment days, the schedule may be slightly different and the
 study staff will discuss this with you.

 -  Radiation therapy will be given Monday through Friday. This will take about 30 minutes,
 including about 10-15 minutes for the radiation treatment.

 -  5-fluorouracil will be given by vein, continuously for about 96 hours a week (Monday
 through Friday).

 -  Docetaxel will be given by vein over about 1 hour, 1 time a week (on Mondays).

 5-fluorouracil will be given using a portable pump about the size of a personal CD
 player. You will need to carry this portable pump with you for about 96 hours each week.

 Docetaxel will be given through a central venous catheter. A central venous catheter is a
 sterile flexible tube that will be placed into a large vein while you are under local
 anesthesia. Your doctor will explain this procedure to you in more detail, and you will be
 required to sign a separate consent form for this procedure. The catheter will be removed at
 the end of Week 5.

 Before every dose of docetaxel, you will receive dexamethasone to lower the risk of side
 effects. Dexamethasone will be given by vein over a few seconds.

 Your doctor will let you know if and when you are eligible to have surgery. In this study,
 the surgery must be performed within 8-10 weeks after you finish chemotherapy and radiation
 therapy. You will be asked to sign a separate consent form that describes the surgery and
 anesthesia (numbing medicine) and their risks in more detail. The screening tests that will
 help your doctor decide if you are eligible to have surgery include the scans and endoscopy
 described below (4-6 weeks after radiation and chemotherapy).

 You will no longer be able to receive radiation and chemotherapy if the disease gets worse or
 intolerable side effects occur. You will not be able to have surgery if the doctor decides
 surgery is not in your best interest (for example, if the disease or your general health gets
 worse).

 Study Visits:

 During Study Therapy:

 Blood (about 3 tablespoons) will be drawn for routine tests during Week 3 of radiation and
 chemotherapy.

 Follow-Up:

 At 4-6 weeks after your last dose of radiation and chemotherapy, the following tests and
 procedures will be performed:

 -  You will have a CT scan of the chest and a whole-body PET/CT scan to check the status of
 the disease.

 -  You may have an endoscopy of your esophagus with 1 or more biopsies of the tumor to
 check the status of the disease. The number of biopsies you have will be the doctor's
 decision at the time of the procedure, based on the status and location of the disease.

 -  Blood (about 3 tablespoons) will be drawn for routine tests.

 -  You will fill out 3 quality-of-life questionnaires. This should take about 10-15
 minutes.

 About 4 weeks after surgery, you will fill out 3 quality-of-life questionnaires. You will
 then fill out 2 quality-of-life questionnaires at 6 of your routine follow-up visits after
 surgery.

 Every 3-6 months in the first 3 years after your last dose of radiation and chemotherapy,
 then every 6 months in the next 2 years, and every year after that from then on, the
 following tests and procedures will be performed:

 -  You will have a CT scan of the chest or a whole-body PET/CT scan to check the status of
 the disease.

 -  You will have an endoscopy of your esophagus to check the status of the disease during
 every follow-up visit in Year 1. After that, you will have an endoscopy of your
 esophagus at follow-up visits anytime the doctor decides it is needed. You will have 1
 or more tumor biopsies at these follow-up visits if the doctor decides they are needed,
 based on the status and location of the disease. This will be decided at the time of the
 endoscopy.

 Biomarker Testing:

 If leftover tumor tissue is available from before you joined the study, the leftover tissue
 will be used for genetic biomarker testing. If you do not have leftover tumor tissue
 available from before you joined the study, leftover tissue from study procedures will be
 used for genetic biomarker testing.

 This is an investigational study. Docetaxel and 5-fluorouracil are FDA approved and
 commercially available to treat esophageal cancer. However, it is investigational to give
 these drugs to patients with early-stage esophageal cancer.

 It is investigational to give the combination of chemotherapy, radiation therapy, and surgery
 to patients with early-stage esophageal cancer.

 Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:

 1. Histologically documented adenocarcinoma or squamous cell carcinoma of the thoracic
 esophagus or gastroesophageal junction that are staged as T1b using endoscopic
 ultrasound (EUS) or from a large biopsy (either criteria # 1 or #2 can be met for
 eligibility).

 2. Patients who undergo a diagnostic Endoscopic Mucosal Resection (EMR) and have a
 diagnosis of T1b stage established.

 3. Performance score Karnofsky Performance Scale (KPS) 80-100.

 4. Patients should be surgical candidates for esophagectomy and should have no
 contraindications for chemotherapy or radiation.

 5. Negative pregnancy test for women of child bearing potential. They must agree to
 adequate contraception.

 6. Complete blood count (CBC) and complete metabolic panel (chemo-14: Glucose, Calcium,
 Albumin, Total Protein, Sodium, Potassium, CO2, Chloride, Blood Urea Nitrogen (BUN),
 Creatinine, Alkaline Phosphatase, ALT (SGPT), AST (SGOT), and Bilirubin) to assess
 adequate hematologic, renal and hepatic functioning will be obtained. The values are
 as follows: Adequate hematologic (White Blood Count (WBC) >2,500/uL, platelets >
 75,000/uL), renal (creatinine clearance > 50 mL/min), and liver function (bilirubin
 <=1.5 fold the upper limit of normal and liver enzymes < 3 fold the upper limit of
 normal).

 7. Based on the risk factors and propensity of lymph node metastasis (LNM) and poorer
 survivals seen in retrospective studies as discussed in the introduction, only
 patients with any one (1) of high risk features such as LVI, tumors >1.2 cm, and high
 grade will be enrolled (Grade is the pathologic term defining the degree of
 differentiation. Grade 1 is well differentiated, Grade 2 is moderately differentiated,
 and Grade 3 is poorly differentiated).

 Exclusion Criteria:

 1. Prior radiation to the chest

 2. Previous or concomitant cancers other than 1) curatively treated carcinoma in situ of
 cervix, basal cell of the skin, curative treatment for transitional cell carcinoma of
 the bladder, and early stage cancers at another non-overlapping site that was treated
 more than 3 years ago for cure.

 3. Pregnant or breast-feeding females

 4. Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic,
 gastrointestinal or hematologic disease but not limited to: a) active uncontrolled
 infection b) Symptomatic congestive heart failure, unstable angina, or cardiac
 dysrrhythmia not controlled by pacer device c) no myocardial infarction within 3
 months of registration

 5. Known hypersensitivity to docetaxel, 5-fluorouracil, polysorbate-80, or any component
 of the formulation