Phase II Study of Fluorine-18 3'-Deoxy-3'-Fluorothymidine (F-18-FLT) in Invasive Breast Cancer

Phase 2

Completed

Conditions: Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IIB Breast Cancer
Stage IIIA Breast Cancer

Interventions: Procedure: CT
Drug: 18F-FLT
Procedure: PET

Registration Number: NCT00572728

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial studies how well 3'-deoxy-3'-18F fluorothymidine (18F-FLT) positron emission tomography (PET)/computed tomography (CT) works in predicting response in patients receiving chemotherapy and undergoing surgery for breast cancer that has spread from where it started to nearby tissue or lymph nodes. Diagnostic procedures, such as 18F-FLT PET/CT, may help in learning how well chemotherapy works to kill breast cancer cells before surgery and help doctors plan the best treatment.

Detailed Description: PRIMARY OBJECTIVES:

I. To correlate the percentage change in standardized uptake value at 60 minutes (SUV60) between baseline (FLT-1) and early-therapy (FLT-2) with pathologic complete response to neoadjuvant chemotherapy of the primary tumor in patients with locally advanced breast cancer.

SECONDARY OBJECTIVES:

I. To demonstrate correlation between FLT-1 and post-therapy (FLT-3) uptake parameters and tumor proliferation markers in locally advanced breast cancer.

II. To evaluate the relationship between FLT-1, FLT-2 and FLT-3 uptake parameters and pathologic complete response of the primary tumor and residual cancer burden (RCB).

III. To evaluate the relationship between FLT-1, FLT-2 and FLT-3 uptake parameters and non-response of the primary tumor (stable or progressive disease) to therapy.

IV. To evaluate the relationship between FLT-1, FLT-2 and FLT-3 uptake parameters and pathologic complete response to neoadjuvant chemotherapy in patients with regional disease in the lymph nodes in patients with locally advanced breast cancer.

V. To compare the changes of FLT-2 and FLT-3 uptake parameters to changes in tumor sizes from other serial imaging modalities such as mammograms, magnetic resonance imaging (MRI), and ultrasound.

VI. To compare the changes of FLT-2 and FLT-3 uptake parameters to metabolic changes from \[18F\] fludeoxyglucose (FDG)-PET, as available.

VII. To continue to monitor for potential safety issues and define any physiologic effects associated with 18F FLT administration.

OUTLINE:

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 90

Inclusion Criteria

Pathologically confirmed breast cancer, determined to be a candidate for primary systemic (neoadjuvant) therapy and for surgical resection of residual primary tumor following completion of neoadjuvant therapy
Locally advanced breast cancer, not stage IV, and with a tumor size >= 2 cm (as measured on imaging or estimated by physical exam)
No obvious contraindications for primary chemotherapy
Residual tumor planned to be removed surgically following completion of neoadjuvant therapy
Able to lie still for 1.5 hours for PET scanning
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Leukocytes >= 3,000/ul
Absolute neutrophil count >= 1,500/ul
Platelets >= 100,000/ul
Total bilirubin within normal institutional limits
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times the institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
If female, postmenopausal for a minimum of one year, OR surgically sterile, OR not pregnant, confirmed by institutional standard of care (SOC) pregnancy test, and willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation
Able to understand and willing to sign a written informed consent document and a Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines

Exclusion Criteria

Previous treatment (chemotherapy, radiation, or surgery) to involved breast; including hormone therapy
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Medically unstable
Condition requiring anesthesia for PET scanning and/or unable to lie still for 1.5 hours
History of allergic reactions attributed to compounds of similar chemical or biologic composition to F-18 fluorothymidine
Pregnant or nursing
Previous malignancy, other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, from which the patient has been disease free for less than 5 years
Currently on hormone therapy as the primary systemic neoadjuvant therapy

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (18F-FLT)	CT	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.
Diagnostic (18F-FLT)	PET	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.
Diagnostic (18F-FLT)	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.

Primary Outcome Measures

Name	Time	Method
%Change in FLT Uptake Between the Baseline (Pre-therapy) and the Early-therapy Imaging Studies to Predict Pathological Complete Response	Baseline (FLT-1) to early therapy (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

Secondary Outcome Measures

Name	Time	Method
Correlation Between SUVmax and Ki-67 LI at FLT1(Baseline PET)	Baseline (FLT-1)	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.
Correlation Between SUVmax and Ki-67 LI at FLT3 (Post-NAC)	Post-NAC (FLT3)	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.
SUVmax at FLT-1 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III	Baseline (FLT-1)	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
SUVmax at FLT-2 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III	early treatment (FLT2)	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
SUVmax at FLT-3 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III	post-NAC (FLT-3)	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.
Change in Uptake Between FLT1 and FLT3 to Predict Pathologic Complete Response (pCR) of the Primary Tumor	Baseline (FLT-1) and post-NAC (FLT-3)	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
%Change SUVmax From FLT1-FLT2 to Predict Lymph Node Status at Surgery	Baseline (FLT-1) and Early Therapy (FLT-2)	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.
%Change SUVmax From FLT1-FLT3 to Predict Lymph Node Status at Surgery	Baseline (FLT-1) and post-NAC (FLT-3)	%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.

Trial Locations

Locations (27): Morton Plant Hospital
🇺🇸
Clearwater, Florida, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Scottsdale Medical Imaging Limited
🇺🇸
Scottsdale, Arizona, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Radiology Consultants Inc
🇺🇸
Youngstown, Ohio, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
Westchase Oncology Center
🇺🇸
Houston, Texas, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Hospital of The University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pennsylvania School of Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
American College of Radiology Imaging Network
🇺🇸
Philadelphia, Pennsylvania, United States
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
Morton Plant Mease
🇺🇸
Dunedin, Florida, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center at Washington University
🇺🇸
Saint Louis, Missouri, United States
Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
Penn State Milton S Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Excel Diagnostics
🇺🇸
Houston, Texas, United States