CHFR Methylation Status Esophageal Cancer Study
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Intervention: Paclitaxel; Cisplatin; Oxaliplatin; 5-Fluorouracil; Radiotherapy; Esophagectomy
Intervention description: Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29.; Paclitaxel and cisplatin:
Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29.
Cisplatin 30 mg/m² days 1, 8, 15, 22, 29.
Cisplatin and 5-fluorouracil:
5-Fluorouracil 1000 mg/m2 per day over 24 hours days 1- 4 and 29 - 32.
Cisplatin 75 mg/m² days 1, 29.; Oxaliplatin 85 mg/m2 days 1, 15, 29.; Oxaliplatin and 5-fluorouracil:
Oxaliplatin 85 mg/m2 days 1, 15, 29.
5-Fluorouracil 180 mg/m2 prolonged infusion starting day 1 of radiation and completing on the final day of radiation (up to 40 days)
Cisplatin and 5-fluorouracil:
5-Fluorouracil 1000 mg/m2 per day over 24 hours days 1-4 and 29-32.
Cisplatin 75 mg/m² days 1, 29.; Patients will be treated 5 days/week at 1.8 Gy/day to a total dose of 45Gy.; The type of resection (Ivor-Lewis, Transhiatal, etc.) will be left to the discretion of the operating surgeon. Resection will be completed between 5 and 8 weeks starting from the completion of chemotherapy and radiation (days 36 - 56).
Intervention MeSH terms: Paclitaxel; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Operable; Based on CHFR Methylation Status; Diagnostic Biopsies

Summary:

      This is a Phase 2 Study of Paclitaxel with Cisplatin versus Fluoropyrimidine with a Platinum
      Agent for Neoadjuvant Therapy in Operable Esophageal Cancer Based on CHFR Methylation Status
      in Diagnostic Biopsies.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed adenocarcinoma of the esophagus or GE junction

          2. Patient must be untreated with chemotherapy, radiation therapy, or surgery for this
             diagnosis of esophageal cancer. (Endoscopy with biopsy and dilation is permitted.)

          3. Tumor must be located between 20 cm from the teeth endoscopically and 2 cm into the
             gastric cardia. Cervical esophageal cancers and true gastric cancers are excluded.

          4. Stage T2-3/N0-3/M0 as determined by imaging studies and biopsy where appropriate. T4
             disease is permitted if defined as resectable by the thoracic surgeon (involvement of
             the pleura, pericardium or diaphragm).

          5. Patients must have had an endoscopic ultrasound

          6. Patients must have had a staging PET scan

          7. Age ≥ 18 and ≤ 75

          8. ECOG performance status 0-1.

          9. Surgically resectable tumor

         10. Patients with a history of a curatively treated malignancy must be disease-free and
             have a survival prognosis that exceeds three years.

         11. Patients must have adequate organ and marrow function as defined below:

               -  absolute neutrophil count ≥ 1,000/mcL

               -  platelets ≥ 100,000/mcL

               -  total bilirubin ≤ 2 mg/dL

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN

               -  creatinine < 1.5 X institutional ULN

         12. Female patients must not be pregnant or breast feeding. Radiotherapy is associated
             with significant birth defects and/or non-viable fetus. Paclitaxel, cisplatin,
             oxaliplatin, and 5-fluorouracil have teratogenic potential. A negative pregnancy test
             is required within 14 days of treatment for all women of childbearing potential. 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 and for the
             duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, the patient should
             inform the treating physician immediately.

         13. Patients must have the ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

          1. Patients may not be receiving any investigational agents.

          2. Incomplete healing from previous major surgery.

          3. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to agents they are assigned to.

          4. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital,
             or St John's Wort; these drugs induce CYP3A and may decrease levels paclitaxel. 5-FU
             is a strong CYP2C9 inducer, and concomitant use with carvedilol, celecoxib,
             fosphenytoin, fluoxetine, phenytoin, warfarin and other CYP2C9 substrates should be
             used with caution.

          5. Uncontrolled, inter-current illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          6. HIV-positive patients on combination antiretroviral therapy are ineligible because
             these patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated.

          7. Patients from whom biopsy tissue cannot be obtained for correlate study analysis.