Vitamin E δ-Tocotrienol Multiple Dose in Healthy Subjects - Full Text View

Purpose

The Principal Investigator believes that Vitamin E δ-Tocotrienol will slow the progression of pancreatic cancer cells. Therefore, the investigators must determine the safety and tolerability of Vitamin E δ-Tocotrienol in healthy participants before administering to cancer patients. The investigators will do this by giving participants a dose of up to1600 mg twice a day, not to exceed 3200 mg total for 14 consecutive days.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: Vitamin E δ-Tocotrienol	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	A Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of Vitamin E δ-Tocotrienol Following Multiple Dose Administration in Healthy Subjects

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer Vitamin E

Drug Information available for: alpha-Tocopherol Tocopherol alpha-Tocopherol succinate Tocopherol acetate dl-alpha-Tocopherol

Genetic and Rare Diseases Information Center resources: Pancreatic Cancer

U.S. FDA Resources

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:

Number of Participants With Treatment Related Adverse Events [ Time Frame: 3 Weeks Per Participant ] [ Designated as safety issue: Yes ]
The primary objective of this study is to evaluate the safety and tolerability of Vitamin E δ-Tocotrienol and to determine the maximum administered dose (MAD) or maximum tolerated dose (MTD) of Vitamin E δ-Tocotrienol administered twice daily for 14 days. Safety analyses and summary tables will include data collected for all subjects who receive at least one dose of study drug.

Secondary Outcome Measures:

Maximum Plasma Concentration (Cmax) of Vitamin E δ-Tocotrienol [ Time Frame: 3 Weeks Per Participant ] [ Designated as safety issue: No ]
To determine the effects of dose on the plasma pharmacokinetic (PK) of Vitamin E δ-Tocotrienol following multiple dose administration in healthy subjects.
Pharmacodynamic (PD) Markers of Vitamin E δ-Tocotrienol Activity in Peripheral Blood [ Time Frame: Day 1, Day 8 Day 14 ] [ Designated as safety issue: No ]
Peripheral blood mononuclear cells will be collected at each time point for examination of biomolecular markers not limited to Erk, p-Erk, AKT, p-AKT, p27, Ki-67, and exportin.


Enrollment:	18
Study Start Date:	October 2011
Estimated Study Completion Date:	May 2015
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Phase I Dose Escalation Each investigator will be provided with adequate supplies of Vitamin E δ -Tocotrienol, which will be supplied as 100-mg, 200-mg, and 400-mg capsules. Vitamin E δ-Tocotrienol will be administered orally once. The dose administered to each subject will be fixed and based on cohort assignment. Doses will be administered at the clinical site during each protocol-defined visit.	Drug: Vitamin E δ-Tocotrienol Vitamin E δ-Tocotrienol will be administered orally as a single agent twice daily for 14 consecutive days. Vitamin E δ-Tocotrienol is supplied as 100-mg, 200-mg, and 400-mg capsules. The first cohort will be dosed with δ-tocotrienol at 100 mg twice daily for 14 consecutive days. A minimum of 3 subjects is planned for each dosing cohort with Vitamin E δ-Tocotrienol dose escalation dependent on safety and available PK data from prior cohorts. At the MTD or MAD, 18 subjects will be enrolled. Other Name: Delta-tocotrienol

Arms

Assigned Interventions

Experimental: Phase I Dose Escalation

Each investigator will be provided with adequate supplies of Vitamin E δ -Tocotrienol, which will be supplied as 100-mg, 200-mg, and 400-mg capsules. Vitamin E δ-Tocotrienol will be administered orally once. The dose administered to each subject will be fixed and based on cohort assignment. Doses will be administered at the clinical site during each protocol-defined visit.

Drug: Vitamin E δ-Tocotrienol

Vitamin E δ-Tocotrienol will be administered orally as a single agent twice daily for 14 consecutive days. Vitamin E δ-Tocotrienol is supplied as 100-mg, 200-mg, and 400-mg capsules. The first cohort will be dosed with δ-tocotrienol at 100 mg twice daily for 14 consecutive days. A minimum of 3 subjects is planned for each dosing cohort with Vitamin E δ-Tocotrienol dose escalation dependent on safety and available PK data from prior cohorts. At the MTD or MAD, 18 subjects will be enrolled.

Other Name: Delta-tocotrienol

Detailed Description:

Participants will be accrued in cohorts of three. The decision to dose escalate will be made by the Cohort Review Committee (CRC) based on safety after the last subject in the current cohort has completed the Study Treatment Period. The study will consist of the following procedures:

Pre-Treatment Period: The screening period must occur within 7 days of dosing.
Study Treatment Period (14 days): Vitamin E δ-Tocotrienol will be administered orally twice daily for 14 consecutive days
Post-Treatment Period: Subject will return to the study site 7 days after the dose of Vitamin E δ-Tocotrienol for an end-of-treatment assessment. On day 8 (± 2 days) after the last dose of study drug, the investigator will obtain follow-up information. Any serious adverse events (SAEs) present at 7 days after the last dose and possibly related to study drug will be followed until resolution, stabilization, or initiation of treatment that confounds the ability to assess the event.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Equal to or greater than 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
Adequate organ function:
- Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥60 mL/min.
- Bilirubin ≤ the intuitional upper limits of normal
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to be within institutional normal range
- Absolute neutrophil count (ANC) ≥1000mm³
- Platelet count ≥100,000mm³
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.
Women of childbearing potential must have a negative pregnancy test at screening.
Able to understand and comply with the requirements of the protocol

Exclusion Criteria:

receiving investigational therapy (other than the investigational therapy under study)
Have 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
Have had prior major surgery within 30 days prior to first dose of study drug
The patient has active infection or fever >38.5C within 3 days prior to first dose of study drug.
Have 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
Unable or unwilling to stop taking vitamins, herbal remedies, or nonprescription medications
Pregnant or breastfeeding
Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01450046

Locations


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

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

National Cancer Institute (NCI)

BioGene Life Science

Investigators


Principal Investigator:	Amit Mahipal, M.D.	H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials website This link exits the ClinicalTrials.gov site

No publications provided


Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT01450046 History of Changes
Other Study ID Numbers:	MCC-16153
Study First Received:	October 7, 2011
Last Updated:	November 17, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:


pancreas gastrointestinal GI prevention vitamin E

Additional relevant MeSH terms:


Pancreatic Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Neoplasms Neoplasms by Site Pancreatic Diseases Alpha-Tocopherol Tocopherols	Tocotrienols Vitamin E Vitamins Antioxidants Growth Substances Micronutrients Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Protective Agents

ClinicalTrials.gov processed this record on February 26, 2015