Oxaliplatin-Based Chemotherapy and Chemoradiotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Carcinoma
Condition: Esophageal Cancer; Gastroesophageal Cancer
MeSH terms: Esophageal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The goal of this clinical research study is to learn if a combination of the investigational
      drug oxaliplatin with 5-Fluorouracil (5-FU) (given at the same time as radiation therapy) is
      as effective as a combination of these two drugs given before and during radiation therapy in
      the treatment of esophageal or gastroesophageal cancers. The safety of these combinations of
      therapy will also be compared.

      Objectives:

      Primary objective:

      Compare the Pathologic Complete Response rate and % of patients with <50% residual cancer in
      the resected surgical specimen between Arms A and B.

      Secondary objectives:

        1. Compare 1-year and 3-year survival rates, median survival time, R0 resection rates,
           safety, and local plus systemic relapse rates between Arms A and B

        2. Perform exploratory correlative studies on blood, adjacent normal and cancer tissue to
           assess predictive markers of response and outcome.

        3. Evaluate the joint effects, including possible interactive effects, of
           proton-versus-photon therapy and treatment arm on overall survival, R0 resection rates,
           safety, and local plus systemic relapse rates.
    

Detailed description: 
      Oxaliplatin and 5-FU are chemotherapy drugs that are commonly used to treat certain kinds of
      cancers. 5-FU is designed to prevent cells from making DNA that is necessary for cell growth.
      This disrupts the growth of the cancer cells, which causes the cancer cells to start to die.
      Oxaliplatin is designed to damage DNA that is already formed.

      If you are found to be eligible to take part in this study, you will be randomly assigned (as
      in the toss of a coin) to one of two groups. Participants in the first group (Arm A) will
      receive chemotherapy with radiation treatment. Participants in the second group (Arm B) will
      receive chemotherapy first then chemotherapy with radiation treatment. The chemotherapy that
      will be used in this study includes 5-FU and oxaliplatin. Arm B is 8 weeks longer than Arm A.
      Your doctor will discuss with you whether you will receive proton or photon radiation. If you
      receive proton radiation, it will be given in a building that is about a 5 minute drive from
      the main MD Anderson radiation clinic.

      All participants will have had a routine upper gastrointestinal tract endoscopy and biopsy
      with endoscopic ultrasound examination before receiving treatment on this study. However,
      once you start on this study, the upper gastrointestinal tract endoscopy will be repeated
      before the 2nd cycle of induction chemotherapy Arm B (if needed), before chemoradiation, and
      before surgery. This procedure involves examination of the esophagus, stomach, and duodenum
      by a flexible tube. Biopsies will be taken as necessary.

      Arm A:

      If you are assigned to Arm A, you will receive treatment with 5-FU over 24 hours for 5 days
      each week for 5 weeks. It will be given as an infusion into a vein using a portable pump.
      This will start on Day 1 (Monday) and will continue until Day 5 (Friday) of each radiotherapy
      week for 5 weeks. You will need to carry this pump with you for about 96 hours. The pump is
      about the size of a personal compact disc player. You will also receive oxaliplatin as an
      infusion into a vein over 2 hours on Day 1. This will be repeated on Days 8, 15, 22, and 29.
      During this time you will receive radiation therapy every weekday for 5 weeks.

      If the cancer gets worse or you experience intolerable side effects, you will be taken off
      the study and your doctor will discuss other treatment options with you.

      Each week while you are receiving chemoradiotherapy, around 1 tablespoon of blood will be
      drawn for routine tests. Between 5-6 weeks after the completion of chemoradiotherapy, the
      stage of the cancer will be evaluated. This includes drawing blood (about 1 tablespoon) for
      routine tests, an Electrocardiography (ECG), a Physical Fitness Testing (PFT), a computed
      tomography (CT) of the abdomen and chest (when necessary), a Positron emission tomography
      (PET) or PET/CT scan, and an upper GI endoscopy with biopsies and checking the status of your
      abdominal disease (if necessary).

      When the evaluation of the status of your disease is complete, surgical removal of the
      primary tumor and lymph nodes will be attempted. All participants with no spreading disease,
      who are physically able to have surgery and have disease that is judged to be removable will
      be eligible for surgery. The tube (J-tube) will be left in your body for at least 8 weeks
      after the surgery to supplement your nutrition.

      Arm B:

      If you are assigned to Arm B, you will receive a starting (induction) course of chemotherapy
      before radiation therapy ever starts. You will receive 5-FU over 48 hours as an infusion into
      a vein using a portable pump. This will start on Day 1 and will continue over 48 hours. This
      will be repeated on Day 15 for another 48 hours. You will need to carry this pump with you at
      all times from Days 1-2 and Days 15-16. The pump is about the size of a personal compact disc
      player. You will also receive oxaliplatin as an infusion into a vein over 2 hours on Days 1
      and 15.

      One cycle is equal to 28 days, which includes 2 doses of 5-FU and oxaliplatin given on Day 1
      and Day 15. Treatment is always followed by 12 days of recovery. You will receive a maximum
      of 2 cycles (4 doses of 5-FU and oxaliplatin).

      After the first and second cycles, you will be given a full physical exam, upper GI x-rays if
      necessary, about 1 tablespoon of blood will be drawn for routine blood tests, and if needed,
      a CT scan of the abdomen and chest will be performed. You will have a PET scan or PET CT scan
      and upper GI endoscopy with biopsy (if needed) before the start of Cycle 2 and after the end
      of Cycle 2. If the disease has not gotten worse after the 1st cycle of induction
      chemotherapy, you will receive the 2nd cycle. An upper gastrointestinal tract endoscopy and
      biopsy will be performed. If the disease gets worse at any stage, you will go straight to
      chemoradiotherapy. If the disease starts to spread, you will be taken off study and your
      doctor will discuss other treatment options with you.

      You will begin to receive chemoradiotherapy no more than 12 days after you complete the last
      dose of induction chemotherapy. You will receive treatment with 5-FU over 24 hours for 5 days
      each week for 5 weeks. It will be given as an infusion into a vein using a portable pump.
      This will start on Day 1 (Monday) and will continue until Day 5 (Friday) of each radiotherapy
      week for 5 weeks. You will need to carry this pump with you at all times for about 96 hours.
      You will also receive oxaliplatin as an infusion into a vein over 2 hours on Day 1. This will
      be repeated on Days 8, 15, 22, and 29. During this time you will receive radiation therapy
      every weekday for 5 weeks.

      If the cancer gets worse or you experience intolerable side effects, you will be taken off
      the study and your doctor will discuss other treatment options with you.

      Each week while you are receiving chemoradiotherapy, around 1 tablespoon of blood will be
      drawn for routine tests. Between 5-6 weeks after the completion of chemoradiotherapy, the
      stage of the cancer will be evaluated. This includes drawing blood (about 1 tablespoon) for
      routine tests, an ECG, a PFT, a CT of the abdomen and chest (when necessary), a PET Scan or
      PET CT Scan, and an upper GI endoscopy with biopsies and checking the status of your
      abdominal disease (if necessary).

      When the evaluation of the status of your disease is complete, surgical removal of the
      primary tumor and lymph nodes will be attempted. All participants with no spreading disease,
      who are physically able to have surgery and have disease that is judged to be removable will
      be eligible for surgery. The a tube (J-tube) will be left in your body for at least 8 weeks
      after the surgery to supplement your nutrition.

      Arms A and B:

      You will be asked to fill out side effect sheets throughout your participation in this
      research study. You will be asked questions regarding nausea, hair loss, fatigue, meals, and
      other questions regarding your daily activities. You will be asked to keep a daily calendar
      while receiving therapy of any type.

      You will be asked to come for follow-up visits at MD Anderson at 3, 6, 9, and 12 months after
      surgery and then every 6 months for 2 years, and then once a year for 2 years. At these
      visits, you will have a full physical exam, and about 1 tablespoon of blood drawn for routine
      tests and a CEA test (carcinoembryonic antigen - a protein made by cancer and normal cells)
      if your CEA level was high in the past. You will also have a PET scan, PET CT scan, or CT of
      the chest and abdomen. You will have an upper GI endoscopy with biopsies 3 months after
      surgery and at other follow-up visits if needed. You may have a CT of the chest and abdomen
      at the 3 month visit if needed.

      This is an investigational study. Oxaliplatin is an investigational drug and is not approved
      in the US for use in the treatment of esophageal and gastroesophageal cancer. The combination
      of these 2 drugs (oxaliplatin + 5-FU) is investigational. All procedures are standard of
      care. A total of up to 126 patients will take part in this study. All will be enrolled at MD
      Anderson.
    

Intervention name(s): 5-Fluorouracil; Oxaliplatin; Radiation Therapy; Surgery
Intervention type(s): Drug; Drug; Radiation; Procedure
Intervention description(s): Arm A = 250 mg/m^2 IV over 24 hours for 5 days weekly for 5 weeks.
Arm B = 2.2 mg/m^2 IV over 48 hours on days 1 and 15.; Arm A: 40 mg/m^2 IV daily over 2 hours for 5 weeks
Arm B: 100 mg/m^2 IV on Day 1 and 15; Radiation treatment every weekday for 5 weeks.; Surgical removal of the primary tumor and lymph nodes following completion of disease status evaluation post chemotherapy and radiation treatments.
Other intervention name(s): 5-FU; Adrucil; Efudex; Eloxatin; RT; XRT
Intervention MeSH terms: Fluorouracil; Oxaliplatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Esophageal Cancer; Gastroesophageal Cancer; Gastroesophageal Junction; Radiation Therapy; 5-Fluorouracil; 5-FU; Adrucil; Efudex; Oxaliplatin