Chemoradiation and Tetrathiomolybdate (TM) in Patients With Esophageal Carcinoma
Condition: Esophageal Carcinoma
MeSH terms: Carcinoma; Esophageal Neoplasms
Intervention: Tetrathiomolybdate (TM); Radiation; Surgery
Intervention description: Tetrathiomolybdate: 20mg p.o. per day with largest meal. This will be started 4-6 weeks post-op, and continued x 2 years or until progression of disease is documented.; Radiation treatments will be administered twice per day with each dose separated by more than 6 hours, on Days 1-5, 8-12 and 15-19.; The persons's esophagus will be surgically removed (esophagectomy) on approximately Day #50.
Intervention MeSH terms: Tetrathiomolybdate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Surgery has been the standard of care for esophageal cancer for many years, with limited
      success. At present, several studies are underway nationwide which utilize chemotherapy
      combined with radiation therapy prior to the usual surgical regimen. Although this treatment
      offers some possibility for improvement of patients with esophageal cancer, there remains a
      significant need for development of new drugs that can substantially impact survival

      Investigators at the University of Michigan have been evaluating inhibitors of tumor blood
      vessel growth (angiogenesis). Specifically, they are evaluating the role of copper in
      angiogenesis. Copper has been shown to be both a requirement and a potent stimulus for
      angiogenesis.

      Previous studies have shown Tetrathiomolybdate (TM) to rapidly lower copper levels in the
      blood. The physicians at the University of Michigan are studying whether the addition of TM
      to the chemoradiation and surgery may increase survival for patients with esophageal cancer.
    

Eligibility criteria:

        Eligibility Requirements

          1. Histologically confirmed adenocarcinoma or squamous cell carcinoma of the esophagus or
             gastroesophageal junction

          2. No prior treatment for the esophageal cancer allowed.

          3. No prior thoracic or upper abdominal radiation.

          4. Disease should be limited to the esophagus and regional lymph nodes. Regional lymph
             nodes are described in Section 4.0. However, celiac node enlargement will be
             acceptable for tumors of the distal esophagus, because they will be included in the
             radiation field.

          5. Disease must be able to be encompassed in a single radiation field.

          6. No medical contraindication to surgery

          7. All treatment is to be administered at the University of Michigan Medical Center.

          8. Karnofsky Performance Status (scoring system used to quantify general well-being and
             activities of daily life; scores range from 0 to 100% where 100% represents perfect
             health and 0 represents death) > 70 %.

          9. Age range: 18 - 75 years old.

         10. Adequate baseline hematopoetic function:

             Platelet count equal to or greater than 100,000/mm3 Absolute granulocyte count equal
             to or greater than 1500/mm3 Hematocrit equal to or greater than 29% (patients may be
             transfused to this level)

         11. Adequate baseline organ function :

             Creatinine clearance >/= 60 mls/min Bilirubin equal to or less than 1.5 x upper limits
             of normal AST (aspartate aminotransferase)/ALT (alanine aminotransferase) equal to or
             less than 2.5 x upper limits of normal

         12. Patients with any complaint of hearing loss should be evaluated with an audiogram. The
             average pure tone average hearing loss from 500-2000Hz should not exceed 30 dB. If it
             does, the patient should be warned that further hearing loss may be very noticeable
             and permanent.

         13. Prior malignancy is acceptable if the patient is considered to be cured. In most cases
             this will mean a 5-year disease-free period. Contact the Principal Investigator for
             any specific question regarding this requirement.

         14. Patients with active infection, serious inter-current medical conditions are
             ineligible, according to the judgment of the investigators.

         15. Pregnant or lactating females are not eligible. Women of childbearing Potential must
             be using contraception throughout the entire period of treatment.

         16. Ability to give informed consent.