FES PET/CT in Predicting Response in Patients With Newly Diagnosed Metastatic Breast Cancer Receiving Endocrine Therapy

PRIMARY OBJECTIVES:

I. To determine the negative predictive value (NPV) of [18F]fluoroestradiol (FES) uptake for
response (clinical benefit) at 6 months in patients with estrogen-receptor positive (ER+)
metastatic breast cancer treated with first-line endocrine therapy.

SECONDARY OBJECTIVES:

I. To determine the test-retest reproducibility of quantitative assessment of tumor FES
uptake by standardized uptake values (SUVs).

II. To evaluate the accuracy of FES-PET/CT for predicting response in patients treated with
first line endocrine therapy for metastatic breast cancer.

III. To evaluate the accuracy of FES-PET/CT for predicting progression-free survival (PFS) in
patients treated with first line endocrine therapy for metastatic breast cancer.

IV. To examine the role of FES-PET/CT in predicting progressive disease (PD) or clinical
benefit (CB), in concert with semi-quantitative interpretation of ER, progesterone receptor
(PgR), and marker of proliferation Ki-67 (Ki-67).

V. To evaluate the relationships among FES uptake, as measured by maximum SUV (SUVmax) and
semi-quantitative ER from immunohistochemistry (IHC).

VI. To evaluate FES SUVmax < 1.5 as the optimal cutpoint for predicting progression-free
survival (PFS) to first line endocrine therapy for metastatic breast cancer.

VII. To determine the percent of eligible patients for whom biopsy is not feasible, i.e.,
determine the clinical utility of indirect assay of ER expression by FES-PET/CT.

VIII. To evaluate the heterogeneity of tumor FES uptake in individual patients defined as
variability in lesion's FES uptake.

OUTLINE:

Between 0 to 30 days before start of endocrine therapy, patients receive F-18 16
alpha-fluoroestradiol intravenously (IV) over 2 minutes and undergo PET/CT. Patients may
undergo a second FES-PET/CT study at least 24 hours after the first study and no later than
10 days after the initial study.

After completion of study, patients are followed up for 6 months and then periodically for up
to 2 years.

Inclusion Criteria:

- Capable and willing to provide informed consent

- Women must not be pregnant or breast-feeding. All females of childbearing potential
must have a blood test or urine study within 7 days prior to FES PET/CT scan and
[18F]-fluorodeoxyglucose (FDG)-PET/CT scan to rule out pregnancy; a female of
childbearing potential is any woman, regardless of sexual orientation or whether they
have undergone tubal ligation, who meets the following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy or

- Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)

- Women of childbearing potential and sexually active males must use an accepted and
effective method of contraception or to abstain from sexual intercourse for the
duration of their participation in the study

- Patient is a postmenopausal woman, man, or premenopausal woman for whom standard
endocrine therapy alone (tamoxifen, aromatase inhibitor [AI], with or without ovarian
suppression or fulvestrant) is planned after FES-PET/CT is completed

- Medically stable as judged by patient's physician

- Life expectancy must be estimated by patient's physician at > 6 months

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-3 (restricted to ECOG performance status [PS] 0-2 if age > 70 years)

- Patient must NOT have a history of allergic reaction attributable to compounds of
similar chemical or biologic composition to 18F-FES

- Patient must NOT be in liver failure as judged by the patient's physician

- Histologically confirmed metastatic breast cancer

- Primary tumor and/or metastatic site must be ER+ and may be progesterone-receptor
positive (PgR+) or progesterone-receptor negative (PgR-) by IHC; patients with a
history of an estrogen-receptor negative (ER-) primary tumor and a documented ER+
metastatic site are eligible

- The pathology report and either (1) tissue (blocks or an unstained slides) or (2) a
photomicrograph of the ER IHC slides from at least one site of metastatic disease
and/or from primary breast cancer must be available for central review and analysis

- NOTE: if photomicrographs are submitted, the submission of hematoxylin and eosin
(H&E), PR and Ki67 IHC's, if performed, are also to be submitted

- Patient must NOT have human epidermal growth factor-2 positive (HER2+) metastatic
disease

- Patient must NOT be planning to receive molecular targeted therapy (such as everolimus
or palbociclib) nor HER2 directed therapy in addition to endocrine therapy

- Patient must NOT have received prior endocrine therapy for metastatic disease (i.e.,
must be first-line endocrine therapy for metastatic disease)

- Patient is not now, and never has received adjuvant endocrine therapy OR patient is
currently receiving or has received adjuvant endocrine therapy in the past, AND
adjuvant endocrine therapy was initiated > 2 years prior to diagnosis of metastatic
disease

- Note: patients who developed metastatic disease while still receiving adjuvant
endocrine therapy must have a planned change in the type of endocrine agent used
for subsequent metastatic disease treatment; patient is not receiving blocking
adjuvant therapy (such as toremifene or tamoxifen) OR patient is receiving
blocking adjuvant therapy, but will stop this therapy a minimum of 60 days prior
to FES-PET/CT while still complying with the study timeline

- Patient must NOT have a history of > 1 line of administered chemotherapy for
metastatic disease and must be off chemotherapy for a minimum of 2 weeks; prior
chemotherapy in the adjuvant setting is allowed

- Disease may be measurable (by Response Evaluation Criteria in Solid Tumors [RECIST]
1.1 criteria) or non-measurable but must be present in at least one non-liver site,
where presence is defined as 1.5 cm or greater and visualized on PET/CT with
[18F]-fluorodeoxyglucose (FDG); patients with effusion only disease or disease only in
the liver are not eligible for the study

- Patient must be able to lie still for a 20-30 minute PET/CT scan

- Patient must NOT weigh more than the maximum weight limit for the table for the PET/CT
scanner at the institution where the study is being performed

- The patient is participating in the trial at an institution which has agreed to
perform the imaging research studies, completed the ECOG-American College of Radiology
Imaging Network (ACRIN) defined scanner qualification procedures and received
ECOG-ACRIN (or current ACRIN) approval