Se-Methyl-Seleno-L- Cysteine (MSC) in Treating Healthy Patients

Phase I Study of Single Oral Dose of Se-Methyl-Seleno-L-Cysteine (MSC) in Adult Men

This randomized phase I trial is studying the side effects and best dose of Se-methyl-seleno-L-cysteine in healthy adult men. Studying samples of blood, urine, and toenail clippings in the laboratory from healthy men receiving Se-methyl-seleno-L-cysteine may help doctors learn more about how Se-methyl-seleno-L-cysteine works in the body.

Study Overview

• Status: Completed
• Conditions: Healthy, no Evidence of Disease
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Other: placebo; Drug: Se-methyl-seleno-L-cysteine

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the toxicity of MSC, given to healthy adult males as a single oral dose.

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetics of single oral doses of MSC in healthy adult male volunteers.

II. To evaluate the baseline selenium content of toenail clippings in healthy adult males.

OUTLINE: This is a multicenter, randomized, placebo controlled, double blind, dose escalation study. Participants are randomized to 1 of 2 arms.

Arm I: Participants receive oral placebo on day 1.

Arm II: Participants receive oral Se-methyl-seleno-l-cysteine (MSC) on day 1. Cohorts of 5 participants receive escalating doses of MSC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 2 of 10 patients experience dose-limiting toxicity.

Participants undergo blood, urine, and toenail clipping collection for pharmacokinetic and correlative studies. Samples are analyzed for plasma protein levels of selenium for proteomic and gene expression, molecular fingerprinting by mass spectrometry, and RNA by gene array analysis.

After completion of study treatment, participants are followed at 7-14 days and at 30 days.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Total body weight between 50 and 115 kg
• Hgb > 12 gm/dl
• Platelets > 100,000/μL
• ANC > 1000/μL
• Creatinine < 1.5 mg/dl
• SGPT and SGOT < 3 X the institutional upper limit of normal (ULN)
• Total bilirubin < 1.5 X the institutional ULN (subjects with a higher level of bilirubin due to a familial metabolism will be considered on an individual basis)
• Life expectancy greater than 2 years
• Male subjects must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and until study completion (i.e., at least two weeks after dose of study drug)
• Ability to understand and the willingness to sign a written informed consent document
• Agree to refrain from use of selenium supplements while on study

Exclusion Criteria:

• Not willing to remain at RPCI, and in follow up, as required
• Presence of medical conditions, which in the opinion of the investigators, would compromise either the subject, or the integrity of the data
• Individuals with a history of active liver or kidney disease within the past 6 months
• Treatment with an investigational drug within 30 days prior to the dose of study drug
• Use of prescription or nonprescription drugs, vitamins, or herbal supplements known to change gastric acidity (e.g., H2-antagonists, proton pump inhibitors, antacids) within 3 days of study drug administration
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MSC (e.g. reaction to other selenium supplements)
• Subjects who have donated 1 unit of blood within 30 days prior to the first dose of MSC
• Subjects with a known history of heavy metal exposure, such as lead, mercury, of arsenic
• ECOG performance status > 1
• AUA total symptom score > 10 (or any individual symptom score of greater than or equal to 4 will exclude the participant)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm I (placebo); Participants receive oral placebo on day 1.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Other: placebo; Given orally; Other Names: PLCB
Experimental: Arm II (Se-methyl-seleno-L-cysteine); Participants receive oral Se-methyl-seleno-l-cysteine (MSC) on day 1. Cohorts of 5 participants receive escalating doses of MSC until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 2 of 10 patients experience dose-limiting toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: Se-methyl-seleno-L-cysteine; Given orally; Other Names: MSC; methylselenocysteine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical toxicity in healthy adult male volunteers, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0	Summarized using descriptive statistics.	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the pharmacokinetics of MSC	Descriptive statistics calculated for each cohort, using established pharmacokinetic analysis methods.	Up to 24 hours post-dose
Selenium levels in toenail samples	Summarized graphically.	Up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: June 20, 2007
• First Submitted That Met QC Criteria: June 20, 2007
• First Posted (Estimate): June 21, 2007

Study Record Updates

• Last Update Posted (Estimate): November 14, 2014
• Last Update Submitted That Met QC Criteria: November 13, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; Selenomethylselenocysteine
• Other Study ID Numbers: NCI-2013-00505 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA060553 (U.S. NIH Grant/Contract); N01CN35157 (U.S. NIH Grant/Contract); I 87406; NCI04-4-02; NWU04-4-02 (Other Identifier: DCP)