Clinical trial NCT02398773: FES PET/CT in Predicting Response in Patients With Newly Diagnosed Metastatic Breast Cancer Receiving Endocrine Therapy
Official title: [18F] Fluoroestradiol (FES) PET as a Predictive Measure for Endocrine Therapy in Patients With Newly Diagnosed Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: HER2/Neu Negative
Progesterone Receptor Negative
Progesterone Receptor Positive
Stage IV Breast Cancer AJCC v6 and v7
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2015-03-26
Enrollment: 99
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 F-18 16 alpha-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) in predicting response to endocrine therapy in patients with newly diagnosed breast cancer that has spread to other parts of the body. FES is a radioactive form of the hormone estrogen and may "light up" where cancer is in the body. Diagnostic procedures using FES, such as FES PET/CT, may help measure the FES and help doctors predict how well the cancer will respond to treatment.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Negative predictive value of 18F FES uptake for response (CB), defined as the proportion of patients with a negative FES test result who have progressive disease
timeFrame: At 6 months
Secondary outcomes:
measure: Test-retest reproducibility of quantitative assessment of tumor FES uptake by SUVs
timeFrame: Up to 6 months
measure: FES SUVmax
timeFrame: Up to 6 months
measure: Predictive accuracy of FES PET/CT for PFS, defined as the time from entry onto study until tumor progression or death from any cause
timeFrame: Up to 1 year
measure: Significance of FES PET measures in predicting PD or CB, in concert with semi-quantitative interpretation of ER, PgR, and Ki-67
timeFrame: Baseline
measure: FES uptake, as measured by SUVmax and semi-quantitative ER from IHC
timeFrame: Up to 6 months
measure: FES SUVmax < 1.5 as the optimal cutpoint for predicting PFS
timeFrame: Up to 1 year
measure: Percent of eligible patients for whom biopsy is not feasible, i.e., clinical utility of indirect assay of ER expression by FES PET
timeFrame: Up to 6 months
measure: Heterogeneity of tumor FES uptake in individual patients defined as variability in lesion's FES uptake
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles General Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Sidney and Lois Eskenazi Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Springmill Medical Center
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: East Norriton
country: United States
facility: Fox Chase Cancer Center - East Norriton Hospital Outpatient Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center - University Hospital
state: Wisconsin
city: Mukwonago
country: United States
facility: ProHealth D N Greenwald Center
state: Wisconsin
city: Oconomowoc
country: United States
facility: ProHealth Oconomowoc Memorial Hospital
state: Wisconsin
city: Waukesha
country: United States
facility: ProHealth Waukesha Memorial Hospital
state: Wisconsin
city: Waukesha
country: United States
facility: UW Cancer Center at ProHealth Care
state: Wisconsin
Study officials:
affiliation: ECOG-ACRIN Cancer Research Group
name: Farrokh Dehdashti
role: PRINCIPAL_INVESTIGATOR
References: