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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01015131
First Posted: November 18, 2009
Last Update Posted: February 26, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose
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.

Condition Intervention Phase
Breast Cancer Radiation: 18F-FLT-PET/CT Imaging Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

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. [ Time Frame: Baseline and up to 3 weeks ]
    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. [ Time Frame: Baseline and up to 3 weeks ]
    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. [ Time Frame: Baseline and up to 3 weeks ]
    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. [ Time Frame: Baseline and up to 3 weeks ]
    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. [ Time Frame: Baseline and up to 3 weeks ]
    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. [ Time Frame: Baseline and up to 3 weeks ]
    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. [ Time Frame: Baseline and up to 30 weeks ]
    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. [ Time Frame: Baseline and up to 30 weeks ]
    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. [ Time Frame: Baseline and up to 30 weeks ]
    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. [ Time Frame: Baseline and up to 30 weeks ]
    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. [ Time Frame: Baseline and up to 30 weeks ]
    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.


Enrollment: 46
Study Start Date: April 2010
Study Completion Date: December 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All Participants
18F-FLT-PET imaging
Radiation: 18F-FLT-PET/CT Imaging
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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   35 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01015131


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01015131     History of Changes
Other Study ID Numbers: 0000-139
2009_692 ( Other Identifier: Merck Registration Number )
First Submitted: November 17, 2009
First Posted: November 18, 2009
Results First Submitted: November 6, 2012
Results First Posted: December 20, 2012
Last Update Posted: February 26, 2015
Last Verified: February 2015

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Alovudine
Antiviral Agents
Anti-Infective Agents