Pilot Study Evaluating Sulforaphane in Atypical Nevi-Precursor Lesions

A Pilot Study Evaluation of Sulforaphane in Atypical Nevi--Precursor Lesions: Assessment of STAT1 and STAT3 Risk Markers of Melanoma

This is a pilot study to see if oral administration of freeze dried, powdered broccoli sprouts have any effect on whether moles end up becoming melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma; Atypical Nevi
• Intervention / Treatment: Drug: broccoli sprout extract - sulforaphane (BSE-SFN); Drug: broccoli sprout extract - sulforaphane (BSE-SFN); Drug: broccoli sprout extract - sulforaphane (BSE-SFN)

Detailed Description

This study is designed as a pilot evaluation of sulforaphane as a candidate natural nutritional chemopreventive agent able to modulate key steps in melanoma progression and the expression of STAT proteins in melanocytic and stromal elements of atypical nevi, which are precursor lesions and risk markers of melanoma. Eighteen individuals in total will receive oral broccoli sprout extract rich in sulforaphane (BSE-SFN) standardized for 3 different concentrations of actual sulforaphane content which will be utilized in our study. Three groups of six patients will be randomly assigned to receive oral BSE-SFN at SFN dosages of 50 µmol, 100 µmol, or 200 µmol daily. Due to the established safety of SFN at all of the proposed dosage levels, there is no plan to complete a lower dosage level prior to escalating to the next higher dosage level; i.e., subjects will be randomized across all of the proposed SFN dosage levels. However, the safety of BSE-SFN administration will continue to be evaluated through laboratory studies (CBC, chemistry) performed before and following 28 days of administration.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center

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:

• Subjects must have at least two atypical nevi of ≥ 4 mm diameter and prior diagnosis of melanoma.
• Subjects must be ≥ age 18.
• Subjects must not have received any form of systemic antineoplastic treatment for melanoma within the last year from day 1.
• Subjects should not have known allergies to cruciferous vegetables.
• Subjects must agree to abstain from dietary sources of glucosinolates and isothiocyanates beginning three days prior to study and throughout duration of the active study (28 days). Participants will be asked to keep a food diary. A list of food and supplements to abstain from is provided in Appendix A. Patients will be asked to record instances of accidental ingestion of these foods, with patients being removed from the study if this occurs 7 or more times.
• Female subjects must not be pregnant or breast feeding within 6 months prior to and during course of study.
• CBC including diff & platelets - without clinically significant abnormalities
• CMP (Na, K, Cl, CO2, glucose, BUN, creatinine, calcium, total protein, albumin, AST, ALT, ALK phos, total bilirubin) - within 2x ULN

Exclusion Criteria:

N/A

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose BSE-SFN; BSE-SFN will be orally administered at 50 µmol SFN for 28 days.	Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 50 µmol capsules, taken orally, once a day for 28 days; Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 100 µmol capsules, taken orally, once a day for 28 days; Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 200 µmol capsules, taken orally, once a day for 28 days
Experimental: Mid dose BSE-SFN; BSE-SFN will be orally administered at 100 µmol SFN for 28 days.	Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 50 µmol capsules, taken orally, once a day for 28 days; Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 100 µmol capsules, taken orally, once a day for 28 days; Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 200 µmol capsules, taken orally, once a day for 28 days
Experimental: High dose BSE-SFN; BSE-SFN will be orally administered at 200 µmol SFN for 28 days.	Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 50 µmol capsules, taken orally, once a day for 28 days; Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 100 µmol capsules, taken orally, once a day for 28 days; Drug: broccoli sprout extract - sulforaphane (BSE-SFN); 200 µmol capsules, taken orally, once a day for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events associated with oral sulforaphane	2 years
Visual changes of atypical nevi: size, border, color.	2 years
Cellular changes of the atypical nevi.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Sulforaphane levels in the blood as a result of the 3 doses.	2 years
Effects of sulforaphane on STAT1 and STAT3 expression.	2 years

Collaborators and Investigators

• Sponsor: John Kirkwood
• Investigators: Principal Investigator: John M Kirkwood, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: March 29, 2012
• First Submitted That Met QC Criteria: March 29, 2012
• First Posted (Estimate): April 2, 2012

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: January 7, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: melanoma; sulforaphane; lesions; broccoli; atypical nevi; STAT1; STAT3
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Syndromes, Hereditary; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Nevus; Dysplastic Nevus Syndrome; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; Sulforaphane
• Other Study ID Numbers: 10-114 (University of Pittsburgh Cancer Institute (UPCI))