Trial Outcomes & Findings for Phase II Study of Fluorine-18 3'-Deoxy-3'-Fluorothymidine (F-18-FLT) in Invasive Breast Cancer (NCT NCT00572728)
NCT ID: NCT00572728
Last Updated: 2016-12-30
Results Overview
The primary statistical evaluation will be based on the percent change in FLT SUV60 between baseline (pre-therapy, FLT-1) and the early-therapy imaging (5-10 days after chemotherapy, FLT-2) studies
COMPLETED
PHASE2
90 participants
Baseline (FLT-1) to early therapy (5-10 days after chemotherapy, FLT-2)
2016-12-30
Participant Flow
Participant milestones
| Measure |
Diagnostic (18F-FLT)
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
90
|
|
Overall Study
Eligible
|
87
|
|
Overall Study
Enrolled Under Amendment 5 or Later
|
82
|
|
Overall Study
Did Not Withdraw
|
72
|
|
Overall Study
On Study
|
71
|
|
Overall Study
Completed FLT1 Scan
|
67
|
|
Overall Study
First Therapy Initiated
|
65
|
|
Overall Study
Completed FLT2 Scan
|
60
|
|
Overall Study
Second Chemotherapy Initiated
|
59
|
|
Overall Study
Second Chemotherapy Initiated After FLT2
|
52
|
|
Overall Study
Pathology Complete
|
51
|
|
Overall Study
Completed FLT3 Scan
|
43
|
|
Overall Study
LN Evaluation After NAC
|
38
|
|
Overall Study
RCB Evaluation
|
35
|
|
Overall Study
COMPLETED
|
51
|
|
Overall Study
NOT COMPLETED
|
39
|
Reasons for withdrawal
| Measure |
Diagnostic (18F-FLT)
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
10
|
|
Overall Study
Ineligible
|
3
|
|
Overall Study
Enrolled under Amendment 4
|
5
|
|
Overall Study
Offstudy due to complicating disease
|
1
|
|
Overall Study
FLT1 not completed
|
4
|
|
Overall Study
First Chemotherapy not initiated
|
2
|
|
Overall Study
FLT2 not completed
|
5
|
|
Overall Study
Second chemotherapy not initiated
|
1
|
|
Overall Study
FLT2 after second chemotherapy initiated
|
7
|
|
Overall Study
Pathology missing
|
1
|
Baseline Characteristics
Phase II Study of Fluorine-18 3'-Deoxy-3'-Fluorothymidine (F-18-FLT) in Invasive Breast Cancer
Baseline characteristics by cohort
| Measure |
Diagnostic (18F-FLT)
n=90 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Age, Continuous
|
51 years
n=5 Participants
|
|
Gender
Female
|
90 Participants
n=5 Participants
|
|
Gender
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
75 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
51 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
90 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (FLT-1) to early therapy (5-10 days after chemotherapy, FLT-2)Population: Percent Change in Maximum Standardized FLT uptake between the baseline (pre-therapy, FTL-1) and the early-therapy imaging (5-10 days after chemotherapy, FLT-2)
The primary statistical evaluation will be based on the percent change in FLT SUV60 between baseline (pre-therapy, FLT-1) and the early-therapy imaging (5-10 days after chemotherapy, FLT-2) studies
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=51 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
%Change in FLT Uptake Between the Baseline (Pre-therapy) and the Early-therapy Imaging Studies to Predict Pathological Complete Response
|
38.78 percentage change of SUVmax
Standard Deviation 26.07
|
SECONDARY outcome
Timeframe: Baseline (FLT-1)Population: 1 of the 73 participants did not have both FLT-1 and Ki-67 LI available data
For the purposes of reporting, SUVmax @ FLT1 will be considered the outcome. the correlation is measured between the fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) and SUVmax at FLT1 . Ki-67 labeling index (LI) was calculated as the number of Ki-67 positive tumor cells per one thousand tumor cells.
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=72 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Correlation Between SUVmax and Ki-67 LI at FLT1(Baseline PET)
|
5.71 Standard Uptake Values (SUVmax)
Standard Deviation 3.20
|
SECONDARY outcome
Timeframe: Post-NAC (FLT3)Population: 43 patients who had suitable post-NAC tissue samples for correlation between surgical specimens and FLT3 SUVs
For the purposes of reporting, SUVmax @ FLT-3 will be considered the outcome. correlation between the fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) and SUVmax at FLT-3 Ki-67 labeling index (LI) was calculated as the number of Ki-67 positive tumor cells per one thousand tumor cells.
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=43 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Correlation Between SUVmax and Ki-67 LI at FLT3 (Post-NAC)
|
1.88 Standard Uptake Values (SUVmax)
Standard Deviation 1.88
|
SECONDARY outcome
Timeframe: Baseline (FLT-1)Population: @ Baseline: 35 patients with FLT-1 were evaluable for RCB: 14 patients with RCB 0/I and 21 patients with RCB II/III
While normally RCB (or other final determination) would be considered the outcome, since this is a predictive question, we will consider the Standardized Uptake Values the measurement of interest and report those values herein. Mean Standard Uptake Values (max) at Baseline (FLT-1) were compared for Participants with Residual Cancer Burden 0/I vs Residual Cancer Burden of II/III
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=35 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
SUVmax at FLT-1 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
All Data
|
5.9 Standard Uptake Values (SUVmax)
Standard Deviation 3.2
|
|
SUVmax at FLT-1 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
RCB 0,I
|
6.2 Standard Uptake Values (SUVmax)
Standard Deviation 2.9
|
|
SUVmax at FLT-1 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
RCB II,III
|
5.8 Standard Uptake Values (SUVmax)
Standard Deviation 3.5
|
SECONDARY outcome
Timeframe: early treatment (FLT2)Population: after one cycle of NAC (FLT2): 35 patients had FLT-2 and RCB evaluation: 14 patients with RCB 0/I and 21 patients with RCB II/III
While normally RCB (or other final determination) would be considered the outcome, since this is a predictive question, we will consider the uptake values the measurement of interest and report those values herein. Mean Standard Uptake Values (max) after one cycle of NAC (FLT2) were compared for Participants with Residual Cancer Burden (RCB) 0/I vs RCB II/III
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=35 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
SUVmax at FLT-2 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
All Data
|
3.3 Standard Uptake Values (SUVmax)
Standard Deviation 2.0
|
|
SUVmax at FLT-2 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
RCB 0,I
|
3.5 Standard Uptake Values (SUVmax)
Standard Deviation 2.3
|
|
SUVmax at FLT-2 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
RCB II,III
|
3.2 Standard Uptake Values (SUVmax)
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: post-NAC (FLT-3)Population: After completion of NAC (FLT-3): only 31 patients had both FLT3 and RCB evaluation: 11 patients with RCB 0/I and 20 patients with RCB II/III
The Standard Uptake Values (max) after completion of NAC (FLT-3) were compared for Participants with Residual Cancer Burden 0/I vs Residual Cancer Burden of II/III While normally RCB (or other final determination) would be considered the outcome, since this is a predictive question, we will consider the mean of the uptake values the measurement of interest and report those values herein.
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=31 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
SUVmax at FLT-3 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
All Data (FLT3)
|
1.8 Standard Uptake Values (SUVmax)
Standard Deviation 1.8
|
|
SUVmax at FLT-3 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
RCB 0/I (FLT3)
|
0.7 Standard Uptake Values (SUVmax)
Standard Deviation 0.3
|
|
SUVmax at FLT-3 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
RCB II/III (FLT3)
|
2.4 Standard Uptake Values (SUVmax)
Standard Deviation 2.0
|
SECONDARY outcome
Timeframe: Baseline (FLT-1) and post-NAC (FLT-3)Population: 43 patients who had both FLT1 and FLT3 scans
To evaluate the relationship between the change in uptake between FLT1 and FLT3 and pathologic complete response, an ROC curve will be estimated and the area under the curve (AUC), along with its 90% confidence interval, will be determined. For the purposes of reporting, we will consider the percent change in uptake between FLT1 and FLT3 to be the outcome. Reported values in the Outcome Measure table represent Change in uptake between FLT1 and FLT3, i.e., percentage change of SUVmax. The relationship between the change in uptake between FLT1 and FLT3 and pathological complete response was assessed by using ROC analysis. The Area Under the ROC Curve is reported in the Statistical Analysis section
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=43 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Change in Uptake Between FLT1 and FLT3 to Predict Pathologic Complete Response (pCR) of the Primary Tumor
no-pCR
|
35.8 percentage change in SUVmax
Standard Deviation 26.0
|
|
Change in Uptake Between FLT1 and FLT3 to Predict Pathologic Complete Response (pCR) of the Primary Tumor
All Data
|
38.8 percentage change in SUVmax
Standard Deviation 26.1
|
|
Change in Uptake Between FLT1 and FLT3 to Predict Pathologic Complete Response (pCR) of the Primary Tumor
pCR
|
52.7 percentage change in SUVmax
Standard Deviation 22.8
|
SECONDARY outcome
Timeframe: Baseline (FLT-1) and Early Therapy (FLT-2)Population: Data on 38 patients having FLT1 and FLT2 were available for histopathological LN evaluation after NAC: 14 with negative nodes, 15 with 1-3 LN metastases and 9 with \>3 LN metastases
Reported values in the Outcome Measure table represent %Change in uptake between FLT1 and FLT2, i.e., percentage change of SUVmax. The relationship between the change in uptake between FLT1 and FLT2 and lymph node (LN) status. For the purposes of reporting, the % Change in SUV will be considered the outcome.
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=38 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
%Change SUVmax From FLT1-FLT2 to Predict Lymph Node Status at Surgery
All Data
|
44.9 percent change in SUVmax from FLT1-FLT2
Standard Deviation 26.0
|
|
%Change SUVmax From FLT1-FLT2 to Predict Lymph Node Status at Surgery
0 Positive Nodes
|
47.7 percent change in SUVmax from FLT1-FLT2
Standard Deviation 29.0
|
|
%Change SUVmax From FLT1-FLT2 to Predict Lymph Node Status at Surgery
1-3 Positive Nodes
|
43.8 percent change in SUVmax from FLT1-FLT2
Standard Deviation 23.8
|
|
%Change SUVmax From FLT1-FLT2 to Predict Lymph Node Status at Surgery
3+ Positive Nodes
|
42.6 percent change in SUVmax from FLT1-FLT2
Standard Deviation 27.4
|
SECONDARY outcome
Timeframe: Baseline (FLT-1) and post-NAC (FLT-3)Population: Data on 30 patients with FLT3 were available for histopathological LN evaluation after NAC: 11 with negative nodes, 13 with 1-3 LN metastases and 6 with \>3 LN metastases
%change in SUVmax from FLT1-FLT3 will be compared by lymph node status at surgery For the purposes of reporting, %change in SUVmax from FLT1-FLT3 will be consider the outcome.
Outcome measures
| Measure |
Diagnostic (18F-FLT)
n=30 Participants
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
%Change SUVmax From FLT1-FLT3 to Predict Lymph Node Status at Surgery
0 Positive Nodes
|
65.2 percent change in SUVmax from FLT1-FLT3
Standard Deviation 42.2
|
|
%Change SUVmax From FLT1-FLT3 to Predict Lymph Node Status at Surgery
All Data
|
71.4 percent change in SUVmax from FLT1-FLT3
Standard Deviation 29.1
|
|
%Change SUVmax From FLT1-FLT3 to Predict Lymph Node Status at Surgery
1-3 Positive Nodes
|
77.6 percent change in SUVmax from FLT1-FLT3
Standard Deviation 18.1
|
|
%Change SUVmax From FLT1-FLT3 to Predict Lymph Node Status at Surgery
3+ Positive Nodes
|
69.5 percent change in SUVmax from FLT1-FLT3
Standard Deviation 19.5
|
Adverse Events
Diagnostic (18F-FLT)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Diagnostic (18F-FLT)
n=90 participants at risk
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
General disorders
Flushing
|
2.2%
2/90 • Number of events 3
|
|
General disorders
Paresthesia
|
2.2%
2/90 • Number of events 2
|
|
General disorders
Peripheral sensory neopathy
|
2.2%
2/90 • Number of events 2
|
|
General disorders
Fever
|
1.1%
1/90 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
1.1%
1/90 • Number of events 1
|
|
General disorders
Wound Infenction
|
1.1%
1/90 • Number of events 1
|
|
General disorders
Nail discoloration
|
1.1%
1/90 • Number of events 1
|
|
General disorders
Pain in extremity
|
1.1%
1/90 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
1.1%
1/90 • Number of events 1
|
|
Psychiatric disorders
Fatigue
|
1.1%
1/90 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Insomnia
|
1.1%
1/90 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
1.1%
1/90 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
1.1%
1/90 • Number of events 1
|
|
General disorders
Allergic rhinitis
|
1.1%
1/90 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
1.1%
1/90 • Number of events 1
|
|
Infections and infestations
Generalized muscle weakness
|
1.1%
1/90 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60