Clinical trial NCT01497431: Se-Methyl-Seleno-L-Cysteine or Selenomethionine in Preventing Prostate Cancer in Healthy Participants
Official title: Phase I Multiple Dose Study of 12-Week Treatment by Se-Methyl-L-Cysteine(MSC) and L SeMet in Adult Males
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: No Evidence of Disease
Prostate Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2011-12-22
Enrollment: 66
Sex: MALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical toxicity of Se-methyl-seleno-L-cysteine according to the NCI CTCAE version 4.0
timeFrame: Up to 112 days
measure: Clinical toxicity of Se-methyl-L-cysteine compared to selenium after multiple doses, according to the NCI CTCAE version 4.0
timeFrame: Up to 112 days
Secondary outcomes:
measure: Characterization of the pharmacokinetics of Se in the forms Se-methyl-seleno-L-cysteine and selenium at multiple doses
timeFrame: 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
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Northwestern University
name: Raymond Bergan
role: PRINCIPAL_INVESTIGATOR
References: