Chemoradiation and Tetrathiomolybdate (TM) in Patients With Esophageal Carcinoma

NCT00176800 | Completed Phase 2 Results DMC

• 2 other identifiers: UMCC 2001-007HUM 49005 Legacy 2001-0623
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Esophageal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Median Recurrence Free Survival Time

  To measure the time recurrence in patients with esophageal cancer treated with preoperative chemoradiation, surgery, and post-operative tetrathiomolybdate.

  8 years

Secondary Outcomes (2)

• Median Overall Survival Time

  8 years

• Percentage of Patients That Require Dose Modification Due to Toxicity

  8 years

Study Arms (1)

1

EXPERIMENTAL

Paclitaxel is administered intravenously over 1 hour on Days 1, 8, 15, and 22. Cisplatin will then be administered intravenously over 1 hour on Days 1 and 22. Radiation treatments will be given twice/day, on Days 1-5, 8-12 and 15-19. The subject's esophagus will be surgically removed on approximately Day #50. Approximately 4-6 weeks after surgery, the subject will start taking Tetrathiomolybdate, for 2 years or until treatment is no longer working to control your cancer. The subject will have blood drawn weekly while he/she is receiving chemotherapy and radiation prior to their surgery. 4-6 weeks after their surgery (when the subject starts taking Tetrathiomolybdate), a blood test will be performed every other week for 2 times, and monthly thereafter. When the level of copper has been lowered sufficiently an additional blood test and a baseline chest x-ray will be obtained. Additional blood will be drawn and tested every 6 months for the first 2 years.

Drug: Tetrathiomolybdate (TM); Procedure: Radiation; Procedure: Surgery

Interventions

Tetrathiomolybdate (TM) DRUG

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.

1

Radiation PROCEDURE

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.

1

Surgery PROCEDURE

The persons's esophagus will be surgically removed (esophagectomy) on approximately Day #50.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

tetrathiomolybdate; Radiation; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Results Point of Contact

• Title: Dr. Susan Urba, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

surba@umich.edu

734-615-4762

Study Officials

• Susan Urba, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Study Start: November 1, 2001
• Primary Completion: February 1, 2006
• Study Completion: May 1, 2013
• Last Updated: August 22, 2016
• Results First Posted: August 22, 2016

Record last verified: 2016-07

Locations

US (1)