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

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Radiation: 18F-FLT-PET/CT Imaging

• Registration Number: NCT01015131
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-11-17
• Study First Submitted QC: 2009-11-17
• Study First Posted: 2009-11-18
• Study Start: 2010-04-08
• Primary Completion: 2011-05-24
• Study Completion: 2011-12-01
• Results First Submitted: 2012-11-06
• Results First Submitted QC: 2012-12-17
• Results First Posted: 2012-12-20
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-20
• Last Update Posted: 2021-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 46

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All Participants	18F-FLT-PET/CT Imaging	18F-FLT-PET imaging

Primary Outcome Measures

Name	Time	Method
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.	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.
Change From Baseline in 18F-FLT-PET Mean Standardized Uptake Value (SUVmean) After the First Cycle of Standard of Care (SOC) Neo-adjuvant Chemotherapy.	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.
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.	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.
Change From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy.	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.	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).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy.	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.
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.	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.	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.	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.	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.
Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.	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.