Clinical trial NCT00572728: Phase II Study of Fluorine-18 3'-Deoxy-3'-Fluorothymidine (F-18-FLT) in Invasive Breast Cancer
Official title: 3'-Deoxy-3'-18F Fluorothymidine PET/CT in Predicting Response To Chemotherapy Before Surgery in Patients With Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stage IIB Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-12-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: %Change in FLT Uptake Between the Baseline (Pre-therapy) and the Early-therapy Imaging Studies to Predict Pathological Complete Response
timeFrame: Baseline (FLT-1) to early therapy (5-10 days after chemotherapy, FLT-2)
Secondary outcomes:
measure: Correlation Between SUVmax and Ki-67 LI at FLT1(Baseline PET)
timeFrame: Baseline (FLT-1)
measure: Correlation Between SUVmax and Ki-67 LI at FLT3 (Post-NAC)
timeFrame: Post-NAC (FLT3)
measure: SUVmax at FLT-1 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
timeFrame: Baseline (FLT-1)
measure: SUVmax at FLT-2 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
timeFrame: early treatment (FLT2)
measure: SUVmax at FLT-3 Comparison Between Residual Cancer Burden (RCB) 0/I and RCB II/III
timeFrame: post-NAC (FLT-3)
measure: Change in Uptake Between FLT1 and FLT3 to Predict Pathologic Complete Response (pCR) of the Primary Tumor
timeFrame: Baseline (FLT-1) and post-NAC (FLT-3)
measure: %Change SUVmax From FLT1-FLT2 to Predict Lymph Node Status at Surgery
timeFrame: Baseline (FLT-1) and Early Therapy (FLT-2)
measure: %Change SUVmax From FLT1-FLT3 to Predict Lymph Node Status at Surgery
timeFrame: Baseline (FLT-1) and post-NAC (FLT-3)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Medical Imaging Limited
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Dunedin
country: United States
facility: Morton Plant Mease
state: Florida
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Washington University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Youngstown
country: United States
facility: Radiology Consultants Inc
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: American College of Radiology Imaging Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of The University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Excel Diagnostics
state: Texas
city: Houston
country: United States
facility: Westchase Oncology Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: American College of Radiology Imaging Network
name: Lale Kostakoglu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kostakoglu L, Duan F, Idowu MO, Jolles PR, Bear HD, Muzi M, Cormack J, Muzi JP, Pryma DA, Specht JM, Hovanessian-Larsen L, Miliziano J, Mallett S, Shields AF, Mankoff DA; ACRIN 668 Investigative Team. A Phase II Study of 3'-Deoxy-3'-18F-Fluorothymidine PET in the Assessment of Early Response of Breast Cancer to Neoadjuvant Chemotherapy: Results from ACRIN 6688. J Nucl Med. 2015 Nov;56(11):1681-9. doi: 10.2967/jnumed.115.160663. Epub 2015 Sep 10.