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Prevention of Recurrence and Metastasis in Genetically High-Risk Melanomas

Primary Purpose

Malignant Melanoma

Status
Withdrawn
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Fluvastatin
RNA-sequencing
Gene expression profiling
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Melanoma

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Fluvastatin

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    Number of patients who convert from Class 2 to Class 1
    Number of patients who convert from Class 2 to Class 1 profile on retesting

    Full Information

    First Posted
    February 24, 2020
    Last Updated
    July 23, 2020
    Sponsor
    Case Comprehensive Cancer Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04285749
    Brief Title
    Prevention of Recurrence and Metastasis in Genetically High-Risk Melanomas
    Official Title
    Prevention of Recurrence and Metastasis in Genetically High-Risk Melanomas
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2020
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    PI moving to new institution prior to study activation
    Study Start Date
    November 6, 2020 (Anticipated)
    Primary Completion Date
    April 1, 2021 (Anticipated)
    Study Completion Date
    April 1, 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Case Comprehensive Cancer Center

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    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.
    Detailed Description
    This is an open-label, single arm, study assessing the activity of fluvastatin in shifting the transcriptome in melanoma. Subjects with melanoma will be asked to participate and all subjects will receive the study drug, fluvastatin, for 2 weeks. The primary objective of this study to determine whether administration of fluvastatin changes the melanoma transcriptome The secondary objective of this study is to determine whether administration of fluvastatin changes the gene expression profile of Class 2 melanoma to Class 1 melanoma.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Malignant Melanoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Fluvastatin
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Fluvastatin
    Intervention Description
    Fluvastatin PO 80mg QD for 2 weeks
    Intervention Type
    Other
    Intervention Name(s)
    RNA-sequencing
    Intervention Description
    RNA-sequencing will be completed on the original diagnostic biopsy and the final melanoma excision
    Intervention Type
    Other
    Intervention Name(s)
    Gene expression profiling
    Intervention Description
    Gene expression profiling will be completed on the original diagnostic biopsy and the final melanoma excision
    Primary Outcome Measure Information:
    Title
    Genetic profile shift in melanoma transcriptome
    Description
    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
    Time Frame
    Two weeks
    Secondary Outcome Measure Information:
    Title
    Number of patients who convert from Class 2 to Class 1
    Description
    Number of patients who convert from Class 2 to Class 1 profile on retesting
    Time Frame
    Two weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    99 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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. Exclusion Criteria: 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Wesley Yu, MD
    Organizational Affiliation
    University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    This study is a pilot study to help assess the power needed for a larger study and to determine biologic activity. If a larger study is conducted, data will be shared.

    Learn more about this trial

    Prevention of Recurrence and Metastasis in Genetically High-Risk Melanomas

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