Metabolomic and BH3 Profiling of Esophageal Cancers: Identification of Novel Assessment Methods of Treatment Response for Precision Therapy
Condition: Esophageal Cancer; Esophageal Adenocarcinoma; Esophageal Squamous Cell Cancer; Esophageal Neoplasms; Squamous Cell Carcinoma
MeSH terms: Carcinoma, Squamous Cell; Esophageal Neoplasms; Neoplasms, Squamous Cell; Esophageal Squamous Cell Carcinoma
Intervention: Chemoradiotherapy; Esophagectomy
Intervention description: Chemotherapy: Carboplatin (AUC=2)x5 and Paclitaxel (50 mg/m(2))x5 for two cycles. Radiation: a total dose of 40.4 Gray (Gy) will be given in 23 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy.; Minimally-invasive esophagectomy (RAMIE) or traditional open approach if necessary.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Neoadjuvant Chemoradiotherapy (nCRT); Esophagectomy; Tissue or serologic biomarkers

Summary:

      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:

        1. A robotically-assisted, minimally-invasive esophagectomy

        2. 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.
    

Eligibility criteria:

        -  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-C0165.

          -  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 2.

          -  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

        EXCLUSION CRITERIA:

          -  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