Phase 1 Trial of I3C and Sil in Smokers

Status: Active

Description

This phase I trial studies the safety and pharmacokinetic profile of the combination of indole-3-carbinol (I3C) and silibinin. I3C is a chemical found in vegetables, such as broccoli and Brussels sprouts. Silibinin is a chemical in milk thistle. Both I3C and silibinin have been shown to prevent tobacco carcinogen-induced lung tumors in mice. This is the first trial in which the combination will be studied in humans, and the first step in determining whether the combination could have a preventive effect against tobacco carcinogen-induced lung cancer.

Eligibility Criteria

Inclusion Criteria

  • Current smoker of >= 8 cigarettes per day for at least the last 6 months by self-report
  • Hemoglobin >= 9 g/dL for women, >= 10 g/dL for men
  • Platelet count >= 100 x 10^9/L
  • Total bilirubin =< institutional upper limit of normal (=< 1.3 mg/dL for University of Minnesota Medical Center [UMMC])
  • Alanine aminotransferase (ALT) =< 1.5 times institutional upper limit of normal
  • Creatinine =< 1.4 g/dL and estimated glomerular filtration rate (GFR) >= 80 mL/min/1.7m^2
  • Able to understand the experimental nature of the study and provide informed written consent

Exclusion Criteria

  • Daily proton pump inhibitor, H2-blocker (i.e., ranitidine, famotidine), and/or calcium carbonate use
  • History of gastric bypass surgery, gastric banding, bowel resection, malabsorption syndromes such as celiac sprue or pancreatic insufficiency, or other conditions that may affect gastric or intestinal absorption of nutrients
  • Use of tobacco products other than cigarettes (i.e. snuff, snuz, smokeless tobacco, cigars, pipes), within 7 days of study registration
  • Major or chronic medical disease, including heart disease, poorly controlled diabetes, etc., to be adjudicated by the principal investigator
  • Known active malignancy
  • History of aerodigestive malignancies
  • Women who are pregnant, intend to become pregnant within 3 months of study registration, or who are lactating. Women of childbearing potential must have a negative urine pregnancy test within 14 days of starting the assigned intervention
  • Antibiotic use within 2 months of study registration by self-report
  • History of respiratory tract cancer
  • Known allergy to I3C, Sil, or its components
  • Psychiatric and/or social situations that would potentially limit compliance with study requirements

Locations & Contacts

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Naomi Fujioka
Phone: 612-626-6689
Email: fujio002@umn.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Determine the safety of the combination of indole-3-carbinol (I3C) + silibinin (Sil).

II. Determine the pharmacokinetic profile of I3C + Sil.

SECONDARY OBJECTIVES:

I. Determine the effect of I3C, Sil, or I3C + Sil on circulating inflammatory markers such as IL-1beta, TNF-alpha, IL-6, IL-8, Cox-2, prostaglandin E, and C-reactive protein.

II. Determine the effect of I3C, Sil, or I3C + Sil on circulating immunophenotype.

III. Determine the effect of I3C, Sil, or I3C + Sil on protein expression of phosphorylated-Akt (pAkt), pERK, pSTAT3 and NF-kappaB from peripheral blood mononuclear cells (PBMC).

IV. Determine the effect of I3C, Sil, or I3C + Sil on ribonucleic acid (RNA) sequencing from PBMC.

V. Determine the effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in buccal cells, oral cavity cells, and nasal mucosa.

VI. Determine effect of I3C, Sil, or I3C + Sil on fasting glucose, insulin, lipid profile, leptin, body weight and waist circumference.

OUTLINE: Patients are assigned to 1 of 4 dose cohorts.

COHORT I: Patients receive silibinin 720 mg orally (PO) twice daily (BID) for 8 weeks in the absence of unacceptable toxicity.

COHORT II: Patients receive indole-3-carbinol 400 mg PO BID for 8 weeks in the absence of unacceptable toxicity.

COHORT III: Patients receive indole-3-carbinol 400 mg PO BID and silibinin 360 mg PO BID for 8 weeks in the absence of unacceptable toxicity.

COHORT IV: Patients receive indole-3-carbinol 400 mg PO BID and silibinin 720 mg PO BID for 8 weeks in the absence of unacceptable toxicity.

Subjects are followed until resolution of any adverse events, if any.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Prevention

Lead Organization

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Naomi Fujioka

Trial IDs

Primary ID 2017LS075
Secondary IDs NCI-2018-03389
Clinicaltrials.gov ID NCT03687073