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

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.

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