Phase 1 Trial of I3C and Sil in Smokers
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.
- 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
- 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
Contact: Naomi Fujioka
Trial Objectives and Outline
I. Determine the safety of the combination of indole-3-carbinol (I3C) + silibinin (Sil).
II. Determine the pharmacokinetic profile of I3C + Sil.
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
University of Minnesota / Masonic Cancer Center
Secondary IDs NCI-2018-03389
Clinicaltrials.gov ID NCT03687073