Trial Outcomes & Findings for 18F-FLT-PET in Breast Cancer (MK-0000-139) (NCT NCT01015131)

Last Updated: 2021-02-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

Baseline and up to 3 weeks

Results posted on

2021-02-11

Participant Flow

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.

Participant milestones

Participant milestones
Measure	All Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Overall Study STARTED	44
Overall Study COMPLETED	36
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Overall Study Physician Decision	1
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	2
Overall Study Other Protocol Specified Criteria	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=44 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Age, Continuous	50.0 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and up to 3 weeks

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

Outcome measures

Outcome measures
Measure	All Participants n=36 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
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	2.79 SUV Standard Deviation 1.36
Change 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 1	1.78 SUV Standard Deviation 1.03
Change 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 Baseline	1.00 SUV Standard Deviation 0.95

PRIMARY outcome

Timeframe: Baseline and up to 3 weeks

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

Outcome measures

Outcome measures
Measure	All Participants n=36 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Change From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy. Baseline	5.76 SUV Standard Deviation 2.83
Change From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy. End of Cycle 1	3.52 SUV Standard Deviation 2.13
Change From Baseline in 18F-FLT-PET Maximum Standardized Uptake Value (SUVmax) After the First Cycle of SOC Neo-adjuvant Chemotherapy. Change from Baseline	2.24 SUV Standard Deviation 1.99

PRIMARY outcome

Timeframe: Baseline and up to 3 weeks

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

Outcome measures

Outcome measures
Measure	All Participants n=32 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Change From Baseline in Ki-67 Labeling Index After the First Cycle of SOC Neo-adjuvant Chemotherapy. Baseline (n = 36)	57.89 Labeling Index Standard Deviation 28.17
Change From Baseline in Ki-67 Labeling Index After the First Cycle of SOC Neo-adjuvant Chemotherapy. End of Cycle 1	43.81 Labeling Index Standard Deviation 31.80
Change From Baseline in Ki-67 Labeling Index After the First Cycle of SOC Neo-adjuvant Chemotherapy. Change from Baseline	10.53 Labeling Index Standard Deviation 20.64

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=32 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
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.	0.53 Correlation coefficient Interval 0.28 to 0.72

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=32 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
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.	0.46 Correlation coefficient Interval 0.19 to 0.67

SECONDARY outcome

Timeframe: Baseline and up to 3 weeks

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

Outcome measures

Outcome measures
Measure	All Participants n=35 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Change From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy. Baseline (n = 36)	2.34 Proliferation Score Standard Deviation 0.13
Change From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy. End of Cycle 1	2.20 Proliferation Score Standard Deviation 0.21
Change From Baseline in Proliferation Signature Score (PSS) After the First Cycle of SOC Neo-adjuvant Chemotherapy. Change from Baseline	0.15 Proliferation Score Standard Deviation 0.21

SECONDARY outcome

Timeframe: Baseline and up to 30 weeks

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

MRI of participants was used to measure tumor volumes at baseline and after completing chemotherapy, after approximately 11 to 30 weeks of treatment.

Outcome measures

Outcome measures
Measure	All Participants n=36 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy. Baseline	22.74 cm^3 Standard Deviation 30.82
Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy. End of Chemotherapy	6.14 cm^3 Standard Deviation 14.69
Change From Baseline in Tumor Volume at the End of SOC Neo-adjuvant Chemotherapy. Change from Baseline	16.59 cm^3 Standard Deviation 29.57

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	All Participants n=35 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
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.	0.20 Correlation coefficient 90% Confidence Interval 0.21 • Interval -0.09 to 0.45

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	All Participants n=32 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
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.	0.13 Correlation coefficient Interval -0.18 to 0.41

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	All Participants n=36 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
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.	0.22 Correlation coefficient Interval -0.06 to 0.47

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	All Participants n=36 Participants Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
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.	0.20 Correlation coefficient Interval -0.08 to 0.45

Adverse Events

All Participants

Serious events: 8 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants n=44 participants at risk Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Blood and lymphatic system disorders Febrile neutropenia	9.1% 4/44 • Number of events 5
Gastrointestinal disorders Rectal bleeding	2.3% 1/44 • Number of events 1
General disorders Chest pain	4.5% 2/44 • Number of events 2
General disorders Fever	2.3% 1/44 • Number of events 1
Infections and infestations Catheter site infection	2.3% 1/44 • Number of events 1
Investigations Neutrophil count decreased	2.3% 1/44 • Number of events 1
Nervous system disorders Dizziness	2.3% 1/44 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.3% 1/44 • Number of events 1

Other adverse events

Other adverse events
Measure	All Participants n=44 participants at risk Participants who underwent 18-FLT positron emission tomography (PET) and standard of care (SOC) neo-adjuvant chemotherapy
Blood and lymphatic system disorders Anaemia	11.4% 5/44 • Number of events 5
Blood and lymphatic system disorders Neutropenia	38.6% 17/44 • Number of events 34
Gastrointestinal disorders Constipation	20.5% 9/44 • Number of events 10
Gastrointestinal disorders Diarrhoea	9.1% 4/44 • Number of events 6
Gastrointestinal disorders Haemorrhoids	6.8% 3/44 • Number of events 3
Gastrointestinal disorders Heartburn	6.8% 3/44 • Number of events 3
Gastrointestinal disorders Nausea	52.3% 23/44 • Number of events 33
Gastrointestinal disorders Stomatitis	11.4% 5/44 • Number of events 14
General disorders Fatigue	18.2% 8/44 • Number of events 8
General disorders Fever	9.1% 4/44 • Number of events 6
General disorders Mucositis	18.2% 8/44 • Number of events 10
General disorders Oedema	6.8% 3/44 • Number of events 3
General disorders Weakness generalised	6.8% 3/44 • Number of events 3
Immune system disorders Hypersensitivity reaction	6.8% 3/44 • Number of events 3
Infections and infestations Common cold	6.8% 3/44 • Number of events 5
Injury, poisoning and procedural complications Incision site pain	18.2% 8/44 • Number of events 8
Investigations Alanine aminotransferase increased	6.8% 3/44 • Number of events 3
Investigations Haemoglobin decreased	6.8% 3/44 • Number of events 3
Metabolism and nutrition disorders Anorexia	18.2% 8/44 • Number of events 8
Musculoskeletal and connective tissue disorders Bone pain	9.1% 4/44 • Number of events 4
Musculoskeletal and connective tissue disorders Myalgia	27.3% 12/44 • Number of events 14
Nervous system disorders Dizziness	11.4% 5/44 • Number of events 5
Nervous system disorders Headache	11.4% 5/44 • Number of events 5
Nervous system disorders Neuropathy	13.6% 6/44 • Number of events 6
Psychiatric disorders Insomnia	13.6% 6/44 • Number of events 6
Reproductive system and breast disorders Breast pain	6.8% 3/44 • Number of events 3
Reproductive system and breast disorders Postmenopausal symptoms	6.8% 3/44 • Number of events 3
Respiratory, thoracic and mediastinal disorders Cough	11.4% 5/44 • Number of events 5
Respiratory, thoracic and mediastinal disorders Sore throat	13.6% 6/44 • Number of events 7
Skin and subcutaneous tissue disorders Alopecia	9.1% 4/44 • Number of events 4
Skin and subcutaneous tissue disorders Nail changes	13.6% 6/44 • Number of events 6
Skin and subcutaneous tissue disorders Rash	6.8% 3/44 • Number of events 4
Gastrointestinal disorders Dyspepsia	9.1% 4/44 • Number of events 4

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER