FindTrial
Sign In

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

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01015131
Enrollment
46
Registered
2009-11-18
Start date
2010-04-08
Completion date
2011-12-01
Last updated
2021-02-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

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.

Interventions

RADIATION18F-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.

Sponsors

Merck Sharp & Dohme LLC
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
35 Years to 75 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
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 weeksParticipants 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.Baseline and up to 3 weeksParticipants 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 weeksCore 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.Baseline and up to 3 weeksThe 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.Baseline and up to 3 weeksThe 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

MeasureTime frameDescription
Change From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy.Baseline and up to 3 weeksCore 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 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 weeksThe 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 weeksMRI 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.Baseline and up to 30 weeksThe 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 weeksThe 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 weeksThe 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.

Participant flow

Pre-assignment details

After enrollment, 2 of the 46 participants discontinued due to lack of available 3'-deoxy-3'\[18F\]-fluorothymidine (18-FLT), leaving 44 participants as the baseline population.

Participants by arm

ArmCount
All Participants
Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
44
Total44

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyOther Protocol Specified Criteria4
Overall StudyPhysician Decision1
Overall StudyProtocol Violation1
Overall StudyWithdrawal by Subject2

Baseline characteristics

CharacteristicAll Participants
Age, Continuous50.0 years
STANDARD_DEVIATION 9
Sex: Female, Male
Female
44 Participants
Sex: Female, Male
Male
0 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
39 / 44
serious
Total, serious adverse events
8 / 44

Outcome results

Primary

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.

Time frame: Baseline and up to 3 weeks

Population: Participants whose SUV were measured at Baseline and after 1 cycle of chemotherapy

ArmMeasureGroupValue (MEAN)Dispersion
All ParticipantsChange From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy.Baseline5.76 SUVStandard Deviation 2.83
All ParticipantsChange From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy.End of Cycle 13.52 SUVStandard Deviation 2.13
All ParticipantsChange From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy.Change from Baseline2.24 SUVStandard Deviation 1.99
Primary

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.

Time frame: Baseline and up to 3 weeks

Population: Participants whose SUV were measured at Baseline and after 1 cycle of chemotherapy

ArmMeasureGroupValue (MEAN)Dispersion
All ParticipantsChange From Baseline in 18F-FLT-PET Mean Standardized Uptake Value (SUVmean) After the First Cycle of Standard of Care (SOC) Neo-adjuvant Chemotherapy.Baseline2.79 SUVStandard Deviation 1.36
All ParticipantsChange From Baseline in 18F-FLT-PET Mean Standardized Uptake Value (SUVmean) After the First Cycle of Standard of Care (SOC) Neo-adjuvant Chemotherapy.End of Cycle 11.78 SUVStandard Deviation 1.03
All ParticipantsChange From Baseline in 18F-FLT-PET Mean Standardized Uptake Value (SUVmean) After the First Cycle of Standard of Care (SOC) Neo-adjuvant Chemotherapy.Change from Baseline1.00 SUVStandard Deviation 0.95
Primary

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).

Time frame: Baseline and up to 3 weeks

Population: Participants whose Ki-67 Labeling Index were measured at Baseline and after 1 cycle of chemotherapy

ArmMeasureGroupValue (MEAN)Dispersion
All ParticipantsChange From Baseline in Ki-67 Labeling Index After the First Cycle of SOC Neo-adjuvant Chemotherapy.Baseline (n = 36)57.89 Labeling IndexStandard Deviation 28.17
All ParticipantsChange From Baseline in Ki-67 Labeling Index After the First Cycle of SOC Neo-adjuvant Chemotherapy.End of Cycle 143.81 Labeling IndexStandard Deviation 31.8
All ParticipantsChange From Baseline in Ki-67 Labeling Index After the First Cycle of SOC Neo-adjuvant Chemotherapy.Change from Baseline10.53 Labeling IndexStandard Deviation 20.64
Primary

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.

Time frame: Baseline and up to 3 weeks

Population: Participants who had both their changes from baseline in Ki-67 LI and SUVmax determined at the end of Cycle 1 of chemotherapy.

ArmMeasureValue (NUMBER)
All ParticipantsSpearman'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.0.46 Correlation coefficient
Primary

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.

Time frame: Baseline and up to 3 weeks

Population: Participants who had both their changes from baseline in Ki-67 LI and SUVmean determined at the end of Cycle 1 of chemotherapy.

ArmMeasureValue (NUMBER)
All ParticipantsSpearman'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.0.53 Correlation coefficient
Secondary

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.

Time frame: Baseline and up to 3 weeks

Population: Participants who had PSS determined at Baseline and after 1 cycle of chemotherapy

ArmMeasureGroupValue (MEAN)Dispersion
All ParticipantsChange From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy.Baseline (n = 36)2.34 Proliferation ScoreStandard Deviation 0.13
All ParticipantsChange From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy.End of Cycle 12.20 Proliferation ScoreStandard Deviation 0.21
All ParticipantsChange From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy.Change from Baseline0.15 Proliferation ScoreStandard Deviation 0.21
p-value: <0.0190% CI: [0.0932, 0.2111]paired t-test
Secondary

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.

Time frame: Baseline and up to 30 weeks

Population: Participants who had tumors measured by MRI at Baseline and at the end of chemotherapy

ArmMeasureGroupValue (MEAN)Dispersion
All ParticipantsChange From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.Baseline22.74 cm^3Standard Deviation 30.82
All ParticipantsChange From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.End of Chemotherapy6.14 cm^3Standard Deviation 14.69
All ParticipantsChange From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.Change from Baseline16.59 cm^3Standard Deviation 29.57
Secondary

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.

Time frame: Baseline and up to 30 weeks

Population: Participants who had their Ki-67 LI measured after 1 cycle of chemotherapy and their tumors measured at the end of chemotherapy

ArmMeasureValue (NUMBER)
All ParticipantsSpearman'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.0.13 Correlation coefficient
Secondary

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.

Time frame: Baseline and up to 30 weeks

Population: Participants who had their PSS measured after 1 cycle of chemotherapy and their tumors measured at the end of chemotherapy

ArmMeasureValue (NUMBER)Dispersion
All ParticipantsSpearman'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.0.20 Correlation coefficient90% Confidence Interval 0.21
Secondary

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.

Time frame: Baseline and up to 30 weeks

Population: Participants who had their SUVmax measured after 1 cycle of chemotherapy and their tumors measured at the end of chemotherapy

ArmMeasureValue (NUMBER)
All ParticipantsSpearman'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.0.22 Correlation coefficient
Secondary

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.

Time frame: Baseline and up to 30 weeks

Population: Participants who had their SUVmean measured after 1 cycle of chemotherapy and their tumors measured at the end of chemotherapy

ArmMeasureValue (NUMBER)
All ParticipantsSpearman'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.0.20 Correlation coefficient

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026