Clinical trial NCT00809458: Biomarker Study of Neoadjuvant Vitamin E in Patients With Locally Treatable Prostate Cancer
Official title: A Phase III Biomarker Study of Neoadjuvant Vitamin E in Patients With Locally Treatable Prostate Cancer Prior to Prostatectomy or Brachytherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Vitamin E
Prostate Cancer
Alpha-tocopherol (α-tocopherol)
Lead sponsor: New Mexico Cancer Research Alliance
Sponsor class: OTHER
First posted: 2008-12-17
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to find out if vitamin E can help treat prostate cancer. Vitamin E acts primarily as an anti-oxidant. By decreasing the oxidation in the cancer cell, the tumor cells may die. Vitamin E is a commonly used vitamin that has not been approved by the Food and Drug Administration for use in this type of cancer or for any known cancer. This study will test the hypothesis that vitamin E, in the setting of an oxidative stress such as smoking, can reduce prostate cancer related biomarkers in patients with localized prostate cancer in the neoadjuvant setting.

Detailed description: - Prostate Cancer

Prostate cancer is the most common malignancy in American men. It was estimated that nearly 235,000 men in the United States would be diagnosed with prostate cancer and nearly 27,000 men would die. The treatment of localized prostate cancer includes surgery, radiation therapy, or watchful waiting. The relative benefits of these approaches is unclear and treatment choices are individualized and often patient driven. There is currently no proven benefit to receiving preoperative hormonal therapy for patients undergoing radical prostatectomy. As opposed to patients undergoing external beam radiation therapy, for patients undergoing brachytherapy pre treatment hormonal therapy is used in approximately 40% of patients. Thus, these patients offer a unique opportunity to test novel agents in the neoadjuvant setting.

- Vitamin E

The term vitamin E was introduced by Evans and Bishop to describe a dietary factor important for reproduction in rats. Natural vitamin E includes two groups of closely related fat-soluble compounds, the tocopherols and tocotrienols. Eight analogous compounds are widely distributed in nature. Rich, natural sources of vitamin E are edible plant oils. Distinct biological effects of different forms of vitamin E can be distinguished at a molecular level. Vitamin E is the major hydrophobic chain-breaking antioxidant that prevents the propagation of free radical reactions in the lipid components of membranes, vacuoles and plasma lipoproteins.

As an antioxidant, vitamin E acts in cell membranes where it prevents the propagation of free radical reactions. Non-radical oxidation products are formed by the reaction between alpha-tocopheryl radical and other free radicals, which are conjugated to glucuronic acid and excreted through the bile or urine. Vitamin E is transported in plasma lipoproteins.

Most studies of the safety of vitamin E supplementation have lasted for several months or less, so there is little evidence for the long-term safety of vitamin E supplementation. The Food and Nutrition Board of the Institute of Medicine has set an upper tolerable intake level (UL) for vitamin E at 1,000 mg (1,500 IU) for any form of supplementary alpha-tocopherol per day. Based for the most part on the result of animal studies, the Food and Nutrition Board decided that because vitamin E can act as an anticoagulant and may increase the risk of bleeding problems this is the highest dose unlikely to result in bleeding problems (http://dietary-supplements.info.nih.gov/factsheets/vitamin.asp).

The dose of vitamin E used in the Selenium and vitamin E prostate cancer prevention trial (the SELECT trial) was 400 IU per day and thus this is the dose chosen for this study.

Eligibility criteria: Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed prostate cancer.
2. Patients must have localized prostate cancer and have decided to undergo a prostatectomy or brachytherapy.
3. Patient must not be taking supplemental vitamin E.
4. Age \>18 years.
5. Life expectancy of greater than 6 months.
6. ECOG performance status =\< 2.
7. Patients must have normal organ and marrow function as defined below:

   * leukocytes \>= 3,000/mcL
   * absolute neutrophil count \>=1,500/mcL
   * platelets \>=100,000/mcL
   * total bilirubin within normal institutional limits
   * AST/ALT =\< 2.5 X institutional upper limit of normal
   * creatinine =\< 1.5 X normal institutional upper limit of normal
   * INR =\<1.4
   * PTT =\<1.4 X institutional upper limit of normal
8. Patients must have the ability to understand, and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients who have metastatic prostate cancer.
2. Patients may not be receiving any other investigational agents.
3. Patients with a known bleeding diathesis or patients on therapeutic anticoagulation. (This does not include the use of aspirin but refers to warfarin, heparin, or low molecular weight heparins).
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to vitamin E.
5. The patient may not receive a gonadotrophin release agonist (such as goserelin, or leuprolide), or an antiandrogen (such as bicalutamide, flutamide, or nilutamide) during the study.
6. Uncontrolled intercurrent illness that would limit compliance with study requirements.

   * Inclusion of Women and Minorities

     * Only men are eligible for this trial. Members of all races and ethnic groups are eligible for this trial.

Primary outcomes:
measure: Reduce Biomarkers of Prostate Cancer (PSA Blood Level)
timeFrame: 30 days
Secondary outcomes:
measure: Determine the Tolerability/Toxicity of a Short Course of Vitamin E in the Neoadjuvant Setting.
timeFrame: 3 years
measure: Determine Concordance of the Biomarkers in This Setting
timeFrame: 3 years
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico - Cancer Center
state: New Mexico
Study officials:
affiliation: University of New Mexico Cancer Center
name: Ian Rabinowitz, M.D.
role: STUDY_DIRECTOR
affiliation: University of New Mexico
name: Richard Lauer, MD
role: PRINCIPAL_INVESTIGATOR
References: