Clinical Stage 0 Cutaneous Melanoma AJCC v8, Clinical Stage I Cutaneous Melanoma AJCC v8, Clinical Stage II Cutaneous Melanoma AJCC v8, Clinical Stage III Cutaneous Melanoma AJCC v8, Cutaneous Dysplastic Nevus
Conditions
Brief summary
This phase II trial tests how well sulforaphane works in preventing melanoma in patients with multiple atypical moles (nevi) and a prior history of melanoma. Patients with a history of melanoma and multiple atypical nevi are at a significantly increased risk of developing additional melanomas than those without atypical nevi. Prevention measures usually include sun protection, monthly skin self-examinations and regular skin examinations from a doctor. Sulforaphane is a naturally-occurring substance found in many cruciferous vegetables, including broccoli, that may prevent melanoma from forming.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the effects of oral sulforaphane versus (vs) placebo on change in the total area of atypical and common pigmented nevocellular nevi on the posterior trunk at 12 months after randomization as assessed by digital photographic imaging and analysis using Derma-AI image analysis software, specifically assessed in patients treated for the entire 12-month treatment period (per-protocol analysis). SECONDARY OBJECTIVES: I. To evaluate the effects of oral sulforaphane vs placebo on the number of atypical and common pigmented nevocellular nevi with moderate and significant changes in area on the posterior trunk at 12 months after randomization as assessed by digital photographic imaging and analysis using Derma-AI image analysis software, specifically assessed in patients treated for the entire 12-month treatment period (Intent-to-Treat \[ITT\] analysis). II. To determine the effects of 12 months of sulforaphane treatment versus vs placebo on the total area and features of atypical nevi at 12 months, assessed as above in all randomized patients. III. To assess the safety/tolerability of sulforaphane (three Avmacol® Extra Strength \[Nutramax\] tablets once daily over 12 months), assessed per Common Terminology Criteria for Adverse Events (CTCAE), as well as by dosing deviations among all treated patients. EXPLORATORY OBJECTIVES: I. Effects of sulforaphane on inflammation and immunity: Ia. To evaluate the effects of sulforaphane on circulating serum cytokine and chemokine levels, as assessed by multiplex technology (Luminex or similar); Ib. To evaluate the effects of sulforaphane on immune cell infiltration in atypical melanocytic nevocellular nevi, as assessed by traditional histopathology and immunohistochemistry. III. To evaluate dermoscopic features of targeted prespecified atypical melanocytic nevocellular nevi at each timepoint. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive sulforaphane orally (PO) twice daily (BID) for up to 12 months in the absence of unacceptable toxicity. Patients also undergo optional excisional biopsy at baseline, 3 and 12 months and post treatment and blood sample collection throughout study. ARM B: Patients receive placebo PO BID for up to 12 months in the absence of unacceptable toxicity. Patients also undergo optional excisional biopsy at baseline, 3 and 12 months and post treatment and blood sample collection throughout study. After completion of study treatment, patients are followed every 3 months for 24 months from randomization.
Interventions
PROCEDUREBiopsy Procedure
Undergo optional excisional biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
DRUGPlacebo Administration
Given PO
DRUGSulforaphane
Given PO
Sponsors
ECOG-ACRIN Cancer Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must have ≥ 3 clinically atypical nevi, assessed within 30 days prior to randomization, that are consistent with the International Agency for Research on Cancer (IARC) definition as follows. * Must have a diameter of ≥ 5mm in one dimension * Must include a macular component in at least one area * Must have at least two of the following features: ill-defined borders, color variegation, uneven contour, and erythema NOTE: Lesions suspicious for incipient melanoma will be removed and are not intended for the study * Patient must have a prior diagnosis of early-stage melanoma, defined as either melanoma in situ, localized resected stage I-II node negative melanoma, or resected node negative stage III melanoma who in the assessment of their physician have a low risk of relapse of their prior melanoma within one year of randomization * Patient must not be currently on targeted or checkpoint immunotherapy or treated within 365 days prior to randomization * Patient must be ≥ 18 years of age * Patient must not be pregnant. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) * Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 30 days after the last dose of protocol treatment * Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Patients with a prior or concurrent malignancy (other than the melanoma for which they are on this study), whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, are eligible for this trial * Patient must not have a known allergy to cruciferous vegetables * Patients must not use any other sulforaphane-containing dietary supplement during the study period * Patient must not be on any current systemic treatment for melanoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in total area of atypical and common pigmented nevocellular nevi on the posterior trunk | From baseline to 12 months after randomization | Changes in the total area of nevi compared between the arms will be assessed by Derma-AI digital photographic imaging and analysis using image analysis software. The difference in the change of total area of nevi between the two arms will be compared using the Wilcoxon rank sum test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of changed atypical nevi on the posterior trunk | At baseline and 12 months after randomization | The number of changed atypical nevi will be assessed via automated image analysis. The difference in baseline and post-treatment measures will be compared between the two arms using the Wilcoxon rank-sum test. Both intent-to-treat and per-protocol analyses will be conducted. |
| Incidence of adverse events (AEs) | Up to 12 months | Incidence of AEs assessed per Common Terminology Criteria for Adverse Events as well as by dosing deviations. Toxicity rate for individual AEs, categorized AEs and worst degree AEs will be compared between the two arms using the Fisher's exact test. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJohn M Kirkwood
ECOG-ACRIN Cancer Research Group
Outcome results
None listed