Know Cancer

forgot password

A Phase III Biomarker Study of Neoadjuvant Vitamin E in Patients With Locally Treatable Prostate Cancer Prior to Prostatectomy or Brachytherapy

Phase 3
18 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

A Phase III Biomarker Study of Neoadjuvant Vitamin E in Patients With Locally Treatable Prostate Cancer Prior to Prostatectomy or Brachytherapy

- Prostate Cancer

Prostate cancer is the most common malignancy in American men. It is estimated that nearly
235,000 men in the United States will be diagnosed with prostate cancer and nearly 27,000
men will die of prostate cancer in 2006 (Ries, 2006). 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. Approximately 150 prostatectomies are performed at UNM and the Albuquerque NM VA
HEALTH CARE SYSTEM annually. A further 50 brachytherapies are performed at UNM. 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
~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 (Evans, 1922). Natural vitamin E includes two groups of closely
related fat-soluble compounds, the tocopherols and tocotrienols, each with the four , ß,
, and analogs. The eight analogous compounds are widely distributed in nature; rich,
natural sources of vitamin E are edible plant oils. Sunflower seeds contain almost
exclusively -tocopherol, oil from soybeans contains the -, -, and -tocopherol, and palm
oil contains high concentrations of tocotrienols and -tocopherol (Bauernfeind,1980).
Although the antioxidant property of these molecules is similar, distinct biological effects
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 (

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.

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

- Inclusion of Women and Minorities

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Reduce biomarkers of prostate cancer

Outcome Description:

PSA levels will be measured as a sensitive marker of anti-androgenic activity that is a critical endpoint to be measured in this study. PSA blood levels will be determined at the initiation and completion of VE supplementation from blood obtained at these time points. A clinical reference laboratory will perform blood PSA analysis and will be compared with plasma cholesterol levels as a relative control.

Outcome Time Frame:

30 days

Safety Issue:


Principal Investigator

Ian Rabinowitz, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

University of New Mexico Cancer Center


United States: Food and Drug Administration

Study ID:

INST 0808



Start Date:

September 2008

Completion Date:

February 2013

Related Keywords:

  • Prostate Cancer
  • Vitamin E
  • Prostate Cancer
  • Alpha-tocopherol (α-tocopherol)
  • Prostatic Neoplasms



University of New Mexico - Cancer Center Albuquerque, New Mexico  87106