Vitamin E δ-Tocotrienol (VEDT) Single Dose in Healthy Subjects

A Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of Vitamin E δ-Tocotrienol Following Single Dose Administration in Healthy Subjects

This is a Phase 1, open-label, non-randomized, dose-finding, study of Vitamin E δ-Tocotrienol in subjects with resectable pancreatic tumors.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Vitamin E δ-Tocotrienol

Detailed Description

Vitamin E tocotrienols have been shown to exhibit cancer-preventive activities in preclinical studies. Vitamin E tocotrienols are composed of α-, β-, δ-, and γ-tocotrienols. The investigators preclinical studies indicate that δ-tocotrienol possesses the most potent antitumor activity against pancreatic cancer. It is believed that this micronutrient may have a role in the prevention of pancreatic cancer in healthy participants who are at increased risk of developing the disease.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The participant is ≥ 18 years old
• The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

• The participant has adequate organ function as follows:

  • Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min.
  • Bilirubin ≤ the institutional upper limits of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to be within institutional normal range.
  • Absolute neutrophil count (ANC) ≥ 1000mm³
  • Platelet count ≥ 100,000/mm³
• The participant has the capability of understanding the informed consent document and has signed the informed consent document.
• Sexually active participants (male and female) must use medically acceptable methods of contraception during the course of the study.
• Female participants of childbearing potential must have a negative pregnancy test at screening.
• Able to understand and comply with the requirements of the protocol.

Exclusion Criteria:

• The participant is receiving investigational therapy (other than the investigational therapy under study).
• The participant has received investigational therapy within 30 days prior to first dose of study drug.
• Patients who are unable to swallow capsules.
• Patients with prior malignancies, other than squamous or basal cell carcinomas, unless disease free for ≥ 5 years.
• The participant has had prior major surgery within 30 days prior to first dose of study drug.
• The participant has active infection or fever >38.5C within 3 days prior to first dose of study drug.
• The participant has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• The participant is unable or unwilling to stop taking vitamins, herbal remedies, or nonprescription medications.
• The participant is pregnant or breastfeeding.
• The participant is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Vitamin E δ-Tocotrienol will be administered orally as a single agent once. Vitamin E δ-Tocotrienol is supplied as 100-mg, 200-mg, and 400-mg capsules.	Drug: Vitamin E δ-Tocotrienol; The first cohort will be dosed with δ-tocotrienol at 200 mg. A minimum of 3 participants is planned for each dosing cohort with Vitamin E δ-Tocotrienol dose escalation dependent on safety from prior cohorts.; Other Names: Delta-tocotrienol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	The primary objective of this study is to evaluate the safety and tolerability of Vitamin E δ-Tocotrienol and to determine the minimally effective dose (MED) or maximum tolerated dose (MTD) of Vitamin E δ-Tocotrienol administered once. Safety will be assessed by standard clinical findings and laboratory tests. Toxicity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE)v.4.0. Ninety-five percent confidence intervals may be calculated for selected safety and exploratory variables.	3 weeks per participant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Pharmacokinetic (PK) Markers of Vitamin E δ-Tocotrienol	Pharmacokinetic (PK) markers of Vitamin E δ-Tocotrienol in the plasma, urine, and neoplastic tissue of participants with pancreatic neoplasia. To determine the effects of dose on the plasma pharmacokinetic (PK) of Vitamin E δ-Tocotrienol when orally administered as a single dose in healthy subjects. Ninety-five percent confidence intervals may be calculated for selected safety and exploratory variables. Dose escalation will be based on safety and available PK data.	3 weeks per participant
Number of Participants With Pharmacodynamic (PD) Markers of Vitamin E δ-Tocotrienol	Pharmacodynamic (PD) Markers of Vitamin E δ-Tocotrienol in the plasma, urine, and neoplastic tissue of participants with pancreatic neoplasia. To evaluate pharmacodynamic (PD) markers of Vitamin E δ-Tocotrienol activity in peripheral blood. Ninety-five percent confidence intervals may be calculated for selected safety and exploratory variables. Correlative analysis of PD data will be done.	3 weeks per participant

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Cancer Institute (NCI); BioGene Life Science

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: September 28, 2011
• First Submitted That Met QC Criteria: October 4, 2011
• First Posted (Estimate): October 5, 2011

Study Record Updates

• Last Update Posted (Estimate): April 11, 2016
• Last Update Submitted That Met QC Criteria: April 8, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: pancreas; prevention
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; Tocotrienols
• Other Study ID Numbers: MCC-16152