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18F-FLT-PET in Breast Cancer (MK-0000-139)

Primary Purpose

Breast Cancer

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
18F-FLT-PET/CT Imaging
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Breast Cancer

Eligibility Criteria

35 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Has newly-diagnosed stage IIB/IIIA/IIIB locally advanced breast cancer
  • Is eligible for pre-operative (neo-adjuvant) chemotherapy

Exclusion Criteria:

  • Has a contraindication to magnetic resonance imaging (MRI)
  • Any condition that would limit ability to undergo MRI or PET scans
  • Is a nursing mother
  • Has moderate to end-stage renal disease and is not on dialysis or has renal failure on chronic dialysis

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    All Participants

    Arm Description

    18F-FLT-PET imaging

    Outcomes

    Primary Outcome Measures

    Change From Baseline in 18F-FLT-PET Mean Standardized Uptake Value (SUVmean) After the First Cycle of Standard of Care (SOC) Neo-adjuvant Chemotherapy.
    Participants undergo a baseline 18F-FLT-PET/CT scan followed by a magnetic resonance imaging (MRI) scan prior to chemotherapy. These scans are repeated in approximately 2 to 3 weeks, at the end of the first cycle of chemotherapy to derive a standardized uptake value (SUV) of 18F-FLT, which is calculated from the ratio of radioactivity concentration within a region of interest, and the injected dose at the time of injection, divided by body weight. The SUVmean averages the radioactivity values within a region of interest.
    Change From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    Participants undergo a baseline 18F-FLT-PET/CT scan followed by a magnetic resonance imaging (MRI) scan prior to chemotherapy. These scans are repeated in approximately 2 to 3 weeks, at the end of the first cycle of chemotherapy to derive a standardized uptake value (SUV) of 18F-FLT, which is calculated from the ratio of tissue radioactivity concentration within a region of interest, and the injected dose at the time of injection, divided by body weight. The SUVmax measures the maximum radioactivity values within a region of interest.
    Change From Baseline in Ki-67 Labeling Index After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    Core needle biopsies (CNB) are obtained after completing imaging studies at baseline and approximately 2 to 3 weeks later, after the first cycle of chemotherapy. These tissue samples are then used to measure expression of the cell proliferation marker Ki-67, by manually counting percentage positive immunostained cells, denoted the labeling index (LI).
    Spearman's Rank Correlation Coefficient Between Change From Baseline in Ki-67 Labeling Index and Change From Baseline in SUVmean After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Spearman's Rank Correlation Coefficient Between Change From Baseline in Ki-67 Labeling Index and Change From Baseline in SUVmax After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.

    Secondary Outcome Measures

    Change From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    Core needle biopsies (CNBs) obtained at baseline and after approximately 2-3 weeks of treatment, at the end of the first cycle of chemotherapy, are used to measure cell proliferation by a Proliferation Signature Score (PSS). PSS is calculated from the messenger RNA (mRNA) expression of 47 genes that negatively correlate with time to recurrence, and involves taking their average normalized scores. For reference, a database of 16,000 tumors gave a minimum PSS of 1.51 and a maximum PSS of 2.89; where a higher PSS is associated with an increase in proliferation, higher tumor grade and worse outcomes.
    Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    MRI of participants was used to measure tumor volumes at baseline and after completing chemotherapy, after approximately 11 to 30 weeks of treatment.
    Spearman's Rank Correlation Coefficient Between Change From Baseline in PSS After the First Cycle of SOC Neo-adjuvant Chemotherapy, and Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Spearman's Rank Correlation Coefficient Between Change From Baseline in Ki-67 LI After the First Cycle of SOC Neo-adjuvant Chemotherapy, and Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Spearman's Rank Correlation Coefficient Between Change From Baseline in SUVmax After the First Cycle of SOC Neo-adjuvant Chemotherapy, and Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Spearman's Rank Correlation Coefficient Between Change From Baseline in SUVmean After the First Cycle of SOC Neo-adjuvant Chemotherapy, and Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.

    Full Information

    First Posted
    November 17, 2009
    Last Updated
    January 20, 2021
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01015131
    Brief Title
    18F-FLT-PET in Breast Cancer (MK-0000-139)
    Official Title
    A Pilot Study to Evaluate the Correlation Between 18F-FLT-PET Uptake, Ki-67 Immunohistochemistry, and Proliferation Signature in Response to Neo-Adjuvant Chemotherapy in Breast Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    April 8, 2010 (Actual)
    Primary Completion Date
    May 24, 2011 (Actual)
    Study Completion Date
    December 1, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study correlated changes from baseline in Ki-67, an immunohistochemical marker of cell proliferation, with changes from baseline in tumor uptake of 3'-deoxy-3'[18F]-fluorothymidine (18F-FLT) following the first cycle of treatment with standard of care neo-adjuvant therapy in participants with breast cancer.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Breast Cancer

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    46 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    All Participants
    Arm Type
    Experimental
    Arm Description
    18F-FLT-PET imaging
    Intervention Type
    Radiation
    Intervention Name(s)
    18F-FLT-PET/CT Imaging
    Intervention Description
    Participants receive the investigational radiotracer 18F-FLT intravenously and undergo Positron Emission Tomography (PET)/Computed Tomography (CT) scans at the following three times: prior to initiation of chemotherapy, at the end of the first cycle of treatment, and at the conclusion of chemotherapy.
    Primary Outcome Measure Information:
    Title
    Change From Baseline in 18F-FLT-PET Mean Standardized Uptake Value (SUVmean) After the First Cycle of Standard of Care (SOC) Neo-adjuvant Chemotherapy.
    Description
    Participants undergo a baseline 18F-FLT-PET/CT scan followed by a magnetic resonance imaging (MRI) scan prior to chemotherapy. These scans are repeated in approximately 2 to 3 weeks, at the end of the first cycle of chemotherapy to derive a standardized uptake value (SUV) of 18F-FLT, which is calculated from the ratio of radioactivity concentration within a region of interest, and the injected dose at the time of injection, divided by body weight. The SUVmean averages the radioactivity values within a region of interest.
    Time Frame
    Baseline and up to 3 weeks
    Title
    Change From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    Description
    Participants undergo a baseline 18F-FLT-PET/CT scan followed by a magnetic resonance imaging (MRI) scan prior to chemotherapy. These scans are repeated in approximately 2 to 3 weeks, at the end of the first cycle of chemotherapy to derive a standardized uptake value (SUV) of 18F-FLT, which is calculated from the ratio of tissue radioactivity concentration within a region of interest, and the injected dose at the time of injection, divided by body weight. The SUVmax measures the maximum radioactivity values within a region of interest.
    Time Frame
    Baseline and up to 3 weeks
    Title
    Change From Baseline in Ki-67 Labeling Index After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    Description
    Core needle biopsies (CNB) are obtained after completing imaging studies at baseline and approximately 2 to 3 weeks later, after the first cycle of chemotherapy. These tissue samples are then used to measure expression of the cell proliferation marker Ki-67, by manually counting percentage positive immunostained cells, denoted the labeling index (LI).
    Time Frame
    Baseline and up to 3 weeks
    Title
    Spearman's Rank Correlation Coefficient Between Change From Baseline in Ki-67 Labeling Index and Change From Baseline in SUVmean After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    Description
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Time Frame
    Baseline and up to 3 weeks
    Title
    Spearman's Rank Correlation Coefficient Between Change From Baseline in Ki-67 Labeling Index and Change From Baseline in SUVmax After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    Description
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Time Frame
    Baseline and up to 3 weeks
    Secondary Outcome Measure Information:
    Title
    Change From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy.
    Description
    Core needle biopsies (CNBs) obtained at baseline and after approximately 2-3 weeks of treatment, at the end of the first cycle of chemotherapy, are used to measure cell proliferation by a Proliferation Signature Score (PSS). PSS is calculated from the messenger RNA (mRNA) expression of 47 genes that negatively correlate with time to recurrence, and involves taking their average normalized scores. For reference, a database of 16,000 tumors gave a minimum PSS of 1.51 and a maximum PSS of 2.89; where a higher PSS is associated with an increase in proliferation, higher tumor grade and worse outcomes.
    Time Frame
    Baseline and up to 3 weeks
    Title
    Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    Description
    MRI of participants was used to measure tumor volumes at baseline and after completing chemotherapy, after approximately 11 to 30 weeks of treatment.
    Time Frame
    Baseline and up to 30 weeks
    Title
    Spearman's Rank Correlation Coefficient Between Change From Baseline in PSS After the First Cycle of SOC Neo-adjuvant Chemotherapy, and Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    Description
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Time Frame
    Baseline and up to 30 weeks
    Title
    Spearman's Rank Correlation Coefficient Between Change From Baseline in Ki-67 LI After the First Cycle of SOC Neo-adjuvant Chemotherapy, and Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    Description
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Time Frame
    Baseline and up to 30 weeks
    Title
    Spearman's Rank Correlation Coefficient Between Change From Baseline in SUVmax After the First Cycle of SOC Neo-adjuvant Chemotherapy, and Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    Description
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Time Frame
    Baseline and up to 30 weeks
    Title
    Spearman's Rank Correlation Coefficient Between Change From Baseline in SUVmean After the First Cycle of SOC Neo-adjuvant Chemotherapy, and Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
    Description
    The Spearman's rank correlation coefficient was computed by ranking the data and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.
    Time Frame
    Baseline and up to 30 weeks

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    35 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Has newly-diagnosed stage IIB/IIIA/IIIB locally advanced breast cancer Is eligible for pre-operative (neo-adjuvant) chemotherapy Exclusion Criteria: Has a contraindication to magnetic resonance imaging (MRI) Any condition that would limit ability to undergo MRI or PET scans Is a nursing mother Has moderate to end-stage renal disease and is not on dialysis or has renal failure on chronic dialysis
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php

    Learn more about this trial

    18F-FLT-PET in Breast Cancer (MK-0000-139)

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