Pilot Study of Meat-Borne Carcinogens and Pancreatic Cancer

Study Design:

This is a single institution pilot study to recruit 4 patients with operable pancreatic cancer scheduled for a pancreatectomy and 4 age/sex matched normal controls. Both groups will receive a single oral dose of radiolabeled MelQx followed by serial blood draws over an 8 hour period and urine collections over a 24 hour period. In addition, normal pancreatic tissue and normal small bowel tissue will be collected by Tissue Procurement from resected (waste) tissue at the time of pancreatectomy on the 4 pancreatic cancer patients.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Radiation: MeIQx; Procedure: Pancreatectomy

Detailed Description

This is not a therapeutic trial. It is an etiologic investigation of meat-borne carcinogens and possible role in pancreatic cancer.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Cancer cases are eligible for participation if all of the following criteria are met:

• 1. Diagnosis or suspected diagnosis of pancreatic or periampullary cancer that is deemed to be operable and for which a pancreatectomy is planned.
• At least 18 years of age.

• Adequate hepatic function within 4 weeks of study enrollment defined as:

  • Bilirubin ≤ 2 mg/dl
  • aspartate aminotransferase (ALT), alanine aminotransferase (AST), alkaline phosphatase ≤ 2 the upper limit of normal (ULN)
• Females of childbearing potential or males whose partners are of child bearing potential are required to use an effective method of contraception (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 2 weeks after MelQx administration.
• Voluntary written consent before performance of any study-related procedure not part of normal medical care

Healthy controls are eligible for participation if all of the following criteria are met:

• Consider themselves generally healthy.
• At least 18 years of age
• Controls will be gender and age matched within 10 years of cases.

• Adequate hepatic function within 4 weeks of study enrollment defined as:

  • Bilirubin ≤ 2 mg/dl
  • ALT, AST, alkaline phosphatase ≤ 2 the upper limit of normal (ULN)
• Females of childbearing potential or males whose partners are of child bearing potential are required to use an effective method of contraception (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 2 weeks after MelQx administration.
• Voluntary written consent before performance of any study-related procedure not part of normal medical care

Exclusion Criteria:

Cancer cases are not eligible for participation if any of the following criteria are met:

For the purposes of this study to reduce the risk of recruiting a potentially unresectable patient:

• Tumor ≥ 3 cm by scan
• CA-19-9 > 400
• Ascites
• Pregnant or lactating
• Uncontrolled chronic conditions such as: cardiovascular disease, hypertension, angina, congestive obstructive pulmonary disease (COPD) or other conditions which may alter metabolism, other than diabetes.

Healthy controls are not eligible for participation if any of the following criteria are met:

• Pregnant or lactating.
• Uncontrolled chronic conditions such as cardiovascular disease, hypertension, angina, COPD or conditions which may alter metabolism including diabetes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Control Participants; age/sex matched normal controls - the subject will swallow a capsule with a dietary relevant dose of MeIQx	Radiation: MeIQx; On the day of administration, the subject will swallow a capsule with a dietary relevant dose of MeIQx, 21 µg, labeled with a very low level of 14-carbon. The radioactive dose for MeIQx, 0.002 mSv (4.3 µCi), or less than an average dental x-ray.; Other Names: [14C]-MeIQx (2 Amino-3,8-dimethylimidazo[4,5 f]quinoxaline-2-[14C])
Active Comparator: Pancreatic Cancer Patients; Patients with operable pancreatic cancer scheduled for a pancreatectomy at the University of Minnesota Medical Center.	Radiation: MeIQx; On the day of administration, the subject will swallow a capsule with a dietary relevant dose of MeIQx, 21 µg, labeled with a very low level of 14-carbon. The radioactive dose for MeIQx, 0.002 mSv (4.3 µCi), or less than an average dental x-ray.; Other Names: [14C]-MeIQx (2 Amino-3,8-dimethylimidazo[4,5 f]quinoxaline-2-[14C]); Procedure: Pancreatectomy; Patients with operable pancreatic cancer scheduled for a pancreatectomy at the University of Minnesota Medical Center.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Metabolite Profile of Radiolabeled MeIQx in Blood	Metabolite levels will be expressed as the percent of total recovered radioactivity in plasma. Metabolite profiles will be qualitatively compared between cases and controls, which will include the mean, median, standard deviation, range and 90% confidence interval for the major detoxification metabolites.	Pre MeIQx Administration, 1/2, 1, 2, 4, 6, 8 Hours Post MeIQx Administration
Pharmacokinetic Metabolite Profile of Radiolabeled MeIQx in Urine	Metabolite levels will be expressed as the percent of total recovered radioactivity in urine. Metabolite profiles will be qualitatively compared between cases and controls, which will include the mean, median, standard deviation, range and 90% confidence interval for the major detoxification metabolites.	0-4, 4-8 and 8-24 Hours Post MeIQx Administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantify [14C]MeIQx-DNA adducts in human pancreas	In the pancreatic cancer patients, uninvolved/normal resected (waste) tissue from the surgery will be sent to Lawrence Livermore National Laboratory (LLNL) for DNA extraction following previously published methods. New [14C]MeIQx-DNA adducts formed at physiological concentrations will be detected and quantified in resected tissue with highly sensitive accelerator mass spectrometry (AMS).	4-8 Hours Post MeIQx Administration
Quantify ambient adducts in the human pancreas	DNA adducts already present in resected tissue will be quantified and characterized with a newly improved technique, electrospray capillary high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS).	4-8 Hours Post Administration

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Kristin E. Anderson, Ph.D., Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: December 13, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (Estimate): December 15, 2011

Study Record Updates

• Last Update Posted (Estimate): August 22, 2014
• Last Update Submitted That Met QC Criteria: August 21, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Heterocyclic amine carcinogens; meat-borne carcinogens
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 2011NTLS016