Phase I Multiple Dose Study of 12-Week Treatment by Se-Methyl-L-Cysteine (MSC) and L SeMet in Adult Males
40 Years
80 Years
Male
Prostate Cancer
Trial Information
Phase I Multiple Dose Study of 12-Week Treatment by Se-Methyl-L-Cysteine (MSC) and L SeMet in Adult Males
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, selenomethionine, or placebo at the
first dose level orally (PO) on days 1-84.
ARM II: Participants receive Se-methyl-seleno-L-cysteine, selenomethionine, or placebo at
the second dose level PO on days 1-84.
ARM III: Participants receive Se-methyl-seleno-L-cysteine, selenomethionine, or placebo at
the third dose level PO on days 1-84.
Participants undergo plasma and urine sample collection periodically for pharmacokinetic and
pharmacodynamic studies. Samples are also stored for future proteomic and gene expression
studies.
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 oxalo-acetic
transaminase (SGOT) < 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
- Participants who have donated 1 unit of blood within 30 days prior to the first dose
of investigational agent
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)
- 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Outcome Measure:
Clinical toxicity in healthy adult male volunteers according to the NCI CTCAE version 4.0
Outcome Time Frame:
Up to 112 days
Safety Issue:
Yes
Principal Investigator
James Marshall
Investigator Role:
Principal Investigator
Investigator Affiliation:
Northwestern University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-00085
NCT ID:
NCT01497431
Start Date:
November 2011
Completion Date:
Related Keywords:
- Prostate Cancer
- Prostatic Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Vanderbilt University Medical Center | Nashville, Tennessee 37232-2516 |
| Northwestern University | Chicago, Illinois 60611 |
