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

A Phase 2 study testing 18F-FLT-PET/CT Imaging in people with Breast Cancer, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 35 to 75 years, women only
Conditions the study is for: Breast Cancer
What is being tested?: 18F-FLT-PET/CT Imaging
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: No sites listed yet
Study dates: 8 Apr 2010to 1 Dec 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 35 to 75 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

About this study

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

Conditions: Breast Cancer
Being tested: 18F-FLT-PET/CT Imaging
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

18F-FLT-PET/CT ImagingRadiation
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.

Study groups in NCT01015131
Study group	Role	What they receive
All Participants	Experimental	18F-FLT-PET imaging Receives: Radiation: 18F-FLT-PET/CT Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and up to 3 weeks
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.
Measured: Baseline and up to 3 weeks
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).
Measured: Baseline and up to 3 weeks
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.
Measured: Baseline and up to 3 weeks
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.
Measured: Baseline and up to 3 weeks

Secondary outcomes (6)

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.
Measured: Baseline and up to 3 weeks
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.
Measured: Baseline and up to 30 weeks
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.
Measured: Baseline and up to 30 weeks
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.
Measured: Baseline and up to 30 weeks
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.
Measured: Baseline and up to 30 weeks
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.
Measured: Baseline and up to 30 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Apr 20101 Dec 2011

First posted18 Nov 2009 (estimated)
Study start8 Apr 2010
Primary completion24 May 2011
Study completion1 Dec 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01015131
Sponsor's protocol ID: 0000-139
Other IDs: 2009_692
Status last verified: Jan 2021
First submitted: 17 Nov 2009
Last updated: 11 Feb 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01015131
Acronym / sponsor ID: 0000-139
Conditions: Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 8 Apr 2010 (actual)
Primary completion: 24 May 2011 (actual)
Study completion: 1 Dec 2011 (actual)
First posted: 18 Nov 2009 (estimated)
Results: Posted 20 Dec 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
All Participants	Experimental	Radiation: 18F-FLT-PET/CT Imaging18F-FLT-PET imaging

Who may qualify

Ages: 35 to 75 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
18F-FLT-PET/CT ImagingParticipants 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.	Radiation	All Participants

Primary outcome

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.

6 secondary outcomes

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
Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy.
Time frame: Baseline and up to 30 weeks
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
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
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
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

Results and safety

Results posted to the registry on 20 Dec 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Participants	44	36

Primary outcome: 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. Mean (Standard Deviation). Unit: SUV

Measure	All Participants n = 36
Baseline	2.79 (1.36)
End of Cycle 1	1.78 (1.03)
Change from Baseline	1.00 (0.95)

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

Primary outcome: 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. Mean (Standard Deviation). Unit: SUV

Measure	All Participants n = 36
Baseline	5.76 (2.83)
End of Cycle 1	3.52 (2.13)
Change from Baseline	2.24 (1.99)

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

Primary outcome: 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. Mean (Standard Deviation). Unit: Labeling Index

Measure	All Participants n = 32
Baseline (n = 36)	57.89 (28.17)
End of Cycle 1	43.81 (31.80)
Change from Baseline	10.53 (20.64)

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

Primary outcome: 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. Number (90% Confidence Interval). Unit: Correlation coefficient

Measure	All Participants n = 32
Value	0.53 (0.28 to 0.72)

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

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Participants	8 of 44 (18.2%)	39 of 44 (88.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Breast Cancer

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 18F-FLT-PET/CT Imaging in people with Breast Cancer, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01015131.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2021.