Vitamin E δ-Tocotrienol Administered to Subjects With Resectable Pancreatic Exocrine Neoplasia

A Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Vitamin E δ-Tocotrienol Administered to Subjects With Resectable Pancreatic Exocrine Neoplasia

The purpose of this study is to determine the safest dose of the study drug Vitamin E Delta-tocotrienol, how often it should be taken, and how well people with pancreatic tumors tolerate Vitamin E Delta-tocotrienol.

Study Overview

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

Detailed Description

Delta-tocotrienol is a natural Vitamin E compound that has been consumed by humans as a dietary supplement. The Food and Drug Administration (FDA) has not approved it for sale as a drug. Vitamin E Delta-tocotrienol is being investigated for the prevention and treatment of pancreatic tumors. The usefulness of the Vitamin E Delta-tocotrienol in treating human tumors is unknown.

This study consists of the following: (1) a Pre-Treatment Period in which participants are consented and qualified for the study; (2) a Study Treatment Period in which participant will receive Vitamin E δ-Tocotrienol administered orally twice daily for 14 (±2) consecutive days and once on the day of surgery, with associated pharmacokinetic and pharmacodynamic sampling; (3) a Post Treatment Period in which laboratory and physical examinations are performed. Adverse events will be recorded throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 26
• 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 patient has a resectable tumor or cyst arising from the pancreatic exocrine gland (pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm of the pancreas, or mucinous cystic neoplasm of the pancreas) and is undergoing surgical resection of the neoplasm.
• The patient is not a candidate for neoadjuvant chemoradiation therapy (i.e., patients with borderline resectable pancreatic ductal adenocarcinoma who are known to benefit from neoadjuvant treatment regimens).
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• The patient has adequate organ function as follows: Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance >60 mL/min; Bilirubin ≤ the institutional upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement; absolute neutrophil count (ANC) ≥ 1000mm³; Platelet count ≥100,000/mm³.
• The patient has the capability of understanding the informed consent document and has signed the informed consent document.
• Sexually active patients (male and female) must use medically acceptable methods of contraception during the course of the study.
• Female patients 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 patient is receiving concomitant radiotherapy, chemotherapy, other antineoplastic therapy, or investigational therapy (other than the investigational therapy under study).
• The patient has received radiation therapy, chemotherapy, other anti-neoplastic therapy, or investigational therapy within 30 days prior to first dose of study drug.
• The patient has had prior major surgery within 30 days prior to first dose of study drug.
• The patient has active infection or fever >38.5 C within 3 days prior to first dose of study drug.
• The patient 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 patient is unable or unwilling to stop taking vitamins, herbal remedies, or nonprescription medications.
• The patient is pregnant or breastfeeding.
• The patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
• The patient is a candidate for neo-adjuvant radiation therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Phase I Dose Escalation; Vitamin E δ-Tocotrienol will be administered orally as a single agent twice daily for 14 consecutive days and one dose on Day 15.	Drug: Vitamin E δ-Tocotrienol; Vitamin E δ-Tocotrienol is supplied as 100-mg, 200-mg, and 400-mg capsules. The investigator (or designee) will have records of the number of participants treated within a specific cohort and will determine which treatment cohort to assign newly enrolled participants.; Other Names: Delta-tocotrienol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	To determine the recommended Phase II dose of Vitamin E δ-Tocotrienol which will be defined as the biologic effective dose (BED) which induces significant apoptosis in the pancreatic neoplastic cells of resected tumor specimens following oral administration of Vitamin E δ-Tocotrienol twice daily for 14 (± 2)days prior to surgery, and one dose the day of surgery.	12 weeks per participant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	To characterize the safety and tolerability of Vitamin E δ-Tocotrienol when orally administered at up to 5.6 times the predicted biological effective dose (1600mg twice daily) for 14 (± 2) consecutive days and one dose the day of surgery in patients with pancreatic neoplasia.	12 weeks per participant

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Springett GM, Husain K, Neuger A, Centeno B, Chen DT, Hutchinson TZ, Lush RM, Sebti S, Malafa MP. A Phase I Safety, Pharmacokinetic, and Pharmacodynamic Presurgical Trial of Vitamin E delta-tocotrienol in Patients with Pancreatic Ductal Neoplasia. EBioMedicine. 2015 Nov 14;2(12):1987-95. doi: 10.1016/j.ebiom.2015.11.025. eCollection 2015 Dec.

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: September 25, 2009
• First Submitted That Met QC Criteria: September 25, 2009
• First Posted (Estimate): September 28, 2009

Study Record Updates

• Last Update Posted (Estimate): March 1, 2016
• Last Update Submitted That Met QC Criteria: February 29, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: pancreas; resectable; mucinous cystic neoplasm; pancreatic ductal adenocarcinoma; pancreatic tumor; intraductal papillary mucinous neoplasm of the pancreas; pancreatic exocrine neoplasia
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; Tocotrienols
• Other Study ID Numbers: MCC-15630; 1R01CA129227-01A1 (U.S. NIH Grant/Contract)