Prevention of Recurrence and Metastasis in Genetically High-Risk Melanomas

NCT04285749 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: CASE4619
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine whether a medication, fluvastatin, can change melanoma to a state that is less likely to metastasize or recur. Fluvastatin is experimental in this setting because it is not approved by the Food and Drug Administration (FDA) for treatment or prevention of melanoma. However, fluvastatin has been approved by the FDA for treating high cholesterol.

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (1)

• Genetic profile shift in melanoma transcriptome

  The study team will report which of the 28 genes had significant expression changes. A 2-fold change in the appropriate direction with a p-value of at least 0.05 will be considered significant for potential therapeutic value. P-values will be corrected for the false discovery rate using the Benjamini-Hochberg procedure. Fluvastatin successful in shifting the genetic profile in a therapeutic manner if at least half of the 28 genes have significant expression changes

  Two weeks

Secondary Outcomes (1)

• Number of patients who convert from Class 2 to Class 1

  Two weeks

Study Arms (1)

Fluvastatin

EXPERIMENTAL

Participants will receive Fluvastatin for 2 weeks. RNA-sequencing and gene expression profiling will be completed on the original diagnostic biopsy and the final melanoma excision.

Drug: Fluvastatin; Other: RNA-sequencing; Other: Gene expression profiling

Interventions

Fluvastatin DRUG

Fluvastatin PO 80mg QD for 2 weeks

Fluvastatin

RNA-sequencing OTHER

RNA-sequencing will be completed on the original diagnostic biopsy and the final melanoma excision

Fluvastatin

Gene expression profiling OTHER

Gene expression profiling will be completed on the original diagnostic biopsy and the final melanoma excision

Fluvastatin

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed melanoma clinically staged as AJCC Stage 1-3.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Participant having received a statin drug within 1 month of study enrollment.
• Participant receiving any other investigational agents.
• History of adverse reactions (eg. myalgias, transaminitis, or rhabdomyolysis) attributed to compounds of similar chemical or biologic composition to fluvastatin or other agents used in this study.
• Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, liver disease, or psychiatric illness/social situations that would limit compliance with study requirements.
• Participant currently pregnant (as assessed by positive pregnancy test prior to enrollment) or breastfeeding
• Pregnant or breastfeeding women are excluded from this study because Fluvastatin has the potential for teratogenic or abortifacient effects. Women of childbearing potential will be asked to take a pregnancy test prior to enrollment (unless a pregnancy test administered within the last month is present in the medical record and is negative). A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. Men do not need to use contraception while taking this medication.
• Participants currently receiving BRAF inhibitors, MEK inhibitors, immunotherapy, or any other non-surgical treatment for melanoma.
• Participants currently receiving nucleoside reverse transcriptase inhibitors. These participants are excluded because use of NRTIs may confound the transcriptome measurements used in this study since as described above they are predicted to modify melanoma gene expression.
• Any condition or situation that, in the investigator's opinion, may put the patient at significant risk, or may significantly interfere with the patient's participation in the study.
• Participants concurrently taking macrolide antibiotics (eg erythromycin, clarithromycin), azole antifungals (eg itraconazole, ketoconazole), protease inhibitors (eg ritonavir, telaprevir), gemfibrozil, cyclosporine, danazol, amiodarone, amlodipine, verapamil, diltiazem, azithromycin, carbamazepine, phenytoin, or rifampin are excluded.
• Participants with baseline ALT greater than 3 times the upper limit of normal.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

MeSH Terms

Conditions

Melanoma

Interventions

Fluvastatin; Base Sequence; Gene Expression Profiling

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Genetic Techniques; Investigative Techniques

Study Officials

• Wesley Yu, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: February 26, 2020
• Study Start: November 6, 2020
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: July 27, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share