Se-Methyl-Seleno-L-Cysteine or Selenomethionine in Preventing Prostate Cancer in Healthy Participants

Prostate Carcinoma Clinical Trial

Official title:

Phase I Multiple Dose Study of 12-Week Treatment by Se-Methyl-L-Cysteine(MSC) and L SeMet in Adult Males

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01497431
• Other study ID #: NCI-2012-00085
• Secondary ID: NCI-2012-00085CD
• Status: Completed
• Phase: Phase 1
• First received: December 20, 2011
• Last updated: November 25, 2014
• Start date: November 2011
• Est. completion date: July 2014

Study information

• Verified date: November 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized phase I trial studies the side effects and the best dose of Se-methyl-seleno-L-cysteine or selenomethionine in preventing prostate cancer in healthy participants. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of Se-methyl-seleno-L-cysteine or selenomethionine, two different types of selenium compounds, may prevent prostate cancer from forming.

Description:

PRIMARY OBJECTIVES:

I. To determine the individual toxicity profiles of Se-methyl-seleno-L-cysteine (methyl selenocysteine; MSC) and selenomethionine (SeMet) administered to cohorts of men daily for twelve weeks, with dose escalation with each successive cohort.

SECONDARY OBJECTIVES:

I. To measure the pharmacokinetics of selenium, according to form (MSC vs SeMet): MSC and SeMet impacts on plasma, albumin, and urinary concentrations of selenium over 48 hours on dosing days 1 and 84.

II. To evaluate the pharmacodynamics of selenium by form (MSC vs SeMet): plasma, albumin, and urinary Selenoprotein P (Sepp1) concentrations and glutathione peroxidase (GPx) activity over 48 hours on dosing days 1 and 84.

III. To store plasma and formed elements (red cells plus platelets) for future analysis of methyl selenol and other key selenium species, when those assays become available.

OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 3 treatment arms.

ARM I: Participants receive Se-methyl-seleno-L-cysteine orally (PO) on days 1-84.

ARM II: Participants receive selenomethionine PO on days 1-84.

ARM III: Participants receive placebo PO on days 1-84.

After completion of study treatment, patients are followed up on day 112.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: July 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Total body weight between 50 and 115 kg (110 and 250 lbs)

• Hemoglobin (Hgb) > 12 mg/dL

• Platelet count > 100,000/µL

• Absolute neutrophil count (ANC) > 1000/µL

• Creatinine =< institutional upper limit of normal (ULN)

• Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) < 2.0 x ULN

• Total bilirubin =< ULN (participants with a higher level of bilirubin presumed due to familial metabolism will be considered on an individual basis)

• Life expectancy greater than 3 years

• Participants must agree to use adequate contraception (barrier method of birth control; abstinence) from time of screening until study completion (i.e., for at least 2 weeks after last dose of study drug)

• Ability to understand and the willingness to sign a written informed consent document

• Agree to refrain from use of selenium (Se) supplements (other than the 100 mcg dose common in multivitamins) or Se-containing drugs while on study between 30 days before study drug initiation and Day 84

Exclusion Criteria:

• Not willing to remain at Roswell Park Cancer Institute (RPCI), and in follow up, as required

• Presence of medical conditions which, in the opinion of the investigator, would place either the participant or the integrity of the data at risk

• Serum creatinine > ULN, SGOT or SGPT >= 2.0 x ULN, or bilirubin > ULN

• Treatment with an investigational drug within 30 days prior to the dose of study drug

• Use of selenium [Se] supplements greater than the 100 mcg dose common in multivitamins between 30 days before study drug initiation and Day 84

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to investigational agent (e.g., reaction to other Se supplements)

• Participants who have donated 1 unit of blood within 30 days prior to the first dose of investigational agent

• Eastern Cooperative Oncology Group (ECOG) performance status > 1

• Diagnosed with cancer, other than non-melanoma skin cancer, in last 2 years

• Under treatment for any cancer

• Use of glucose-lowering agents or a condition that would make a fast from 10:00 pm the evening before until 11:00 am on days 1 and 84 hazardous

• American Urological Association (AUA) total symptom score > 10 or any individual symptom score of greater than or equal to 4

• Psychiatric illness which would prevent compliance with the intervention or would prevent the patient from providing informed consent

• Medical conditions which in the opinion of the treating physician would make this protocol unreasonably hazardous for the participant

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• No Evidence of Disease
• Prostate Carcinoma
• Prostatic Neoplasms

Intervention

Dietary Supplement:
• Selenium
Given PO

Other:
• Placebo
Given PO
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Drug:
• Methylselenocysteine
Given PO

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical toxicity of Se-methyl-seleno-L-cysteine according to the NCI CTCAE version 4.0	The safety and tolerability data will be summarized using descriptive statistics, by cohort and for all cohorts combined compared to placebo. Reported adverse events will be looked at for possible differences, where appropriate, using graphical methods.	Up to 112 days	Yes
Primary	Clinical toxicity of Se-methyl-L-cysteine compared to selenium after multiple doses, according to the NCI CTCAE version 4.0	The safety and tolerability data will be summarized using descriptive statistics, by cohort and for all cohorts combined compared to placebo. Reported adverse events will be looked at for possible differences, where appropriate, using graphical methods.	Up to 112 days	Yes
Secondary	Characterization of the pharmacokinetics of Se in the forms Se-methyl-seleno-L-cysteine and selenium at multiple doses	The pharmacokinetic variables will be tabulated, and descriptive statistics calculated for each cohort, using established pharmacokinetic analysis methods. Plasma and urine pharmacokinetic parameters will be summarized graphically and by arithmetic or geometric means and coefficients of variations for each cohort.	At baseline, and at and .5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hrs after dosing on days 1 and between days 70 and 84	No