Chemoradiation and Tetrathiomolybdate (TM) in Patients With Esophageal Carcinoma
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.
Description
The pre-study evaluations include a medical history, physical examination, blood laboratory evaluations, and scans to evaluate disease. A CT scan will be performed to measure the size of the subject's tumor(s). The treatment phase of the study includes: 1. Administration of Paclitaxel as an intravenous infusion over 1 hour on Days #1, 8, 15, and 22. 2. Cisplatin will be given as an intravenous infusion after Paclitaxel over 1 hour on Days #1 and 22. 3. Radiation treatments twice per day with each dose separated by more than 6 hours, on Days 1-5, 8-12 and 15-19.
The subject's esophagus will be surgically removed (esophagectomy) on approximately Day #50.
Approximately four to six weeks after surgery, the subject will start taking Tetrathiomolybdate, one pill a day by mouth, for two years or until treatment is no longer working to control your cancer. The dose may need to be increased by 1 pill every 2 weeks, depending on the results of blood tests that are given on a routine basis to help guide the dosing.
Dietary Restrictions: Subjects may not eat shell fish or liver (organ meat) while on study due to high copper content.
Blood draws (approximately 1-2 tablespoons) will be taken weekly while the subject is undergoing chemotherapy and radiation prior to surgery. Prior to your surgery a CT scan will also be administered. Four to six weeks after surgery (when the subject is starting to take Tetrathiomolybdate), a blood test (approximately 1 teaspoon) will be performed every other week for 2 times, and monthly thereafter. This blood test will check for the amount of copper in the subject's blood. When the level of copper has been lowered sufficiently (which will be determined by your physician) an additional blood test and a baseline chest x-ray will be obtained.
Additional blood will be drawn (approximately 1-2 tablespoons) and tested every 6 months for the first 2 years.
There are circumstances under which treatment may be discontinued whether the subject agrees or not. These circumstances include: the subject's tumor gets worse despite the treatment; side effects of the treatment are too dangerous for the subject; new information about the drug becomes available and this information suggests the drug will be ineffective or unsafe for the subject.
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Esophageal Carcinoma
Intervention
Tetrathiomolybdate (TM), Radiation, Surgery
Location
University of Michigan Cancer Center
Ann Arbor
Michigan
United States
48109
Status
Active, not recruiting
Source
University of Michigan Cancer Center
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00176800
- Information obtained from ClinicalTrials.gov on August 21, 2012
Medical and Biotech [MESH] Definitions
Radiosurgery
A radiological stereotactic technique developed for cutting or destroying tissue by high doses of radiation in place of surgical incisions. It was originally developed for neurosurgery on structures in the brain and its use gradually spread to radiation surgery on extracranial structures as well. The usual rigid needles or probes of stereotactic surgery are replaced with beams of ionizing radiation directed toward a target so as to achieve local tissue destruction.
Second-look Surgery
A followup operation to examine the outcome of the previous surgery and other treatments, such as chemotherapy or radiation therapy.
Diverticulosis, Esophageal
A pathological condition characterized by the presence of a number of ESOPHAGEAL DIVERTICULA in the ESOPHAGUS.
Carcinoma, Verrucous
A variant of well-differentiated epidermoid carcinoma that is most common in the oral cavity, but also occurs in the larynx, nasal cavity, esophagus, penis, anorectal region, vulva, vagina, uterine cervix, and skin, especially on the sole of the foot. Most intraoral cases occur in elderly male abusers of smokeless tobacco. The treatment is surgical resection. Radiotherapy is not indicated, as up to 30% treated with radiation become highly aggressive within six months. (Segen, Dictionary of Modern Medicine, 1992)
Carcinoma 256, Walker
A transplantable carcinoma of the rat that originally appeared spontaneously in the mammary gland of a pregnant albino rat, and which now resembles a carcinoma in young transplants and a sarcoma in older transplants. (Stedman, 25th ed)
Clinical Trials
Pre-operative Chemotherapy and Radiation Therapy for Esophageal Carcinoma
Surgery (esophagectomy or removal of the esophagus)has been the standard treatment for cancer of the esophagus. However, evidence suggests that preoperative chemotherapy and radiation the...
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy with radiation therapy before surger...
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Com...
Patients with surgically resectable T1N1M0 or T2-4N any M0 esophageal carcinoma will receive six weeks of induction chemotherapy with weekly irinotecan and cisplatin given weeks 1, 2, 4 an...
Erbitux Combined With Chemo-Radiotherapy in Esophageal Squamous Cell Carcinoma
The purpose of this study is to determine whether the treatment of loco-regional esophageal squamous cell carcinoma with cetuximab in combination with paclitaxel, cisplatin and radiation...
PubMed Articles
Brain metastasis from esophageal carcinoma has been considered rare and survival following esophageal carcinoma with distant metastasis is poor. The purpose of this report was to clarify cumulative in...
Extended Lymphadenectomy in Esophageal Cancer is Debatable.
Surgery is an essential part of the treatment of patients with esophageal carcinoma. However, there is no consensus on whether the surgical technique can be improved to promote better survival outcome...
Esophageal carcinoma is the most rapidly increasing tumor in the United States and has a dismal 15% 5-year survival. Immunotherapy has been proposed to improve patient outcomes; however, no immunocomp...
Salvage radiotherapy in patients with recurrent esophageal carcinoma.
PURPOSE: The feasibility and effectiveness of radiotherapy in the management of recurrent esophageal carcinoma (REC) is reported. PATIENTS...
Purpose: This study was conducted to evaluate the effectiveness and safety of intensity-modulated radiotherapy (IMRT) and concurrent paclitaxel plus cisplatin (TP regimen) for upper esophageal carcino...
