A Phase 2 Study of [18F] Fluoroestradiol (FES) as a Marker of Hormone Sensitivity of Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Estrogen Receptor-positive Breast Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Best Overall Response
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This phase II trial is studying how well F-18 16 alpha-fluoroestradiol (FES) imaging works in predicting response to first-line hormone therapy in women with hormone receptor-positive metastatic breast cancer. Diagnostic procedures, such as FES imaging, may help predict how well patients will respond to hormone therapy and may help plan the best treatment.
Detailed Description
PRIMARY OBJECTIVES: I. Estimate the ability of \[\^18F\] FES positron emission tomography (PET) or PET/computed tomography (CT) uptake at the level of standard uptake value (SUV) \< 1.5 to predict overall response (OR) to first line endocrine therapy for metastatic breast cancer. SECONDARY OBJECTIVES: I. Evaluate the independent role of \[\^18F\] FES in predicting response and time to progression in patients treated with first-line endocrine therapy for metastatic breast cancer. II. Examine the role of \[\^18F\] FES in predicting OR or clinical benefit (CB), in concert with tissue assay of levels of estrogen receptor (ER) messenger ribonucleic acid (mRNA) measured using quantitative polymerase chain reaction (PCR), and semi-quantitative interpretation of estrogen receptor (ER), progesterone receptor (PgR), androgen receptor (AR), and human epidermal growth factor-2 (HER2), in addition to serial measures of hormone levels in plasma. III. Evaluate the relationships among \[\^18F\] FES, semi-quantitative ER from immunohistochemistry (IHC), and ER mRNA as measured by quantitative PCR. IV. Document the safety profile of \[\^18F\] FES PET in newly diagnosed patients with metastatic breast cancer. V. Evaluate FES SUV \< 1.5 as the optimal cutpoint for predicting OR to first-line endocrine therapy for metastatic breast cancer. VI. Estimate the rate of \[\^18F\] FES SUV \< 1.5 in newly diagnosed metastatic breast cancer patients planning a course of endocrine therapy. OUTLINE: Patients undergo \[\^18F\] FES PET scan. Patients also undergo standard clinical fludeoxyglucose F 18 (FDG)-PET or FDG-PET/CT scan up to 14 days prior to \[\^18F\] FES PET scan. After completion of study treatment, patients are followed up for at least 6 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients will have pathologically confirmed invasive breast cancer with clinical, radiographic and/or pathologic evidence of stage IV disease; patients must have tissue blocks available from biopsy of at least one site of metastatic disease and/or from diagnosis of their primary breast cancer
- •Disease may be measurable (by Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) or non-measurable but must be present in at least one non-liver site and imageable on FDG PET scan; in patients with non-measurable disease by RECIST criteria, one of the following may be used to assess and follow disease: MUC-1 antigen level (either cancer antigen \[CA\] 27.29 or carcinoembryonic antigen \[CEA\]) \> 2 x upper limit of normal (ULN), Circulating tumor cell assay \> 5, or FDG-PET SUV \> 2.5 in purely lytic lesions; elevated tumor markers alone are insufficient
- •No prior endocrine therapy for breast cancer or
- •Off adjuvant endocrine therapy for \> 6 months or
- •Greater than 2 years of a single adjuvant endocrine therapy at the time of first recurrence and plan to change to alternate endocrine therapy; use of tamoxifen must be discontinued 6-8 weeks prior to entrance into the study
- •Prior chemotherapy regimens in the adjuvant or neoadjuvant setting are allowed
- •Women treated with adjuvant LHRH (luteinizing hormone-releasing hormone) analog are eligible
- •Be assessed for menopausal status; for study purposes, postmenopausal is defined as:
- •A prior documented bilateral oophorectomy, or
- •A history of at least 12 months without spontaneous menstrual bleeding, or
Exclusion Criteria
- •Patients with a history of prior endocrine therapy for metastatic disease are NOT eligible; adjuvant endocrine therapy for \< 2 years total or discontinued less than 6 months before first disease recurrence also excludes the patient
- •Patients with disease in the liver only are NOT eligible for the study
- •Patients who are HER2/neu positive disease and planning to undergo HER2-directed therapy (trastuzumab or lapatinib) are NOT eligible for the study
- •Pregnant or lactating; women of childbearing potential with either a positive or no pregnancy test at baseline are excluded
- •Visceral crisis characterized by rapidly progressive hepatic or lymphangitic lung metastases
- •History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent
- •Any other life-threatening illness (e.g., serious, uncontrolled concurrent infection or clinically significant cardiac disease - congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication)
- •Unwillingness to give informed consent
- •Medically unstable as judged by the patient's physician
- •Psychological, familial, sociological, or geographical conditions which do not permit compliance with the study protocol
Outcomes
Primary Outcomes
Best Overall Response
Time Frame: Up to 6 months
Patients were expected to start endocrine therapy within 2 weeks of the FES PET scan. Response assessment was evaluated at 3 and 6 months. For patients with at least one site of measurable disease \[per response evaluation criteria in solid tumors (RECIST, version 1.1)\], size-based response criteria were used to assess response. For patients without disease evaluable by RECIST 1.1, largely patients with bone-dominant metastatic breast cancer, serial FDG PET scanning was used to determine response. A decline in the FDG PET SUV (standard uptake value) of 30% or more was considered as response and an increase of 20% or more was considered to be progressive disease (PD). The initial (baseline) FES uptake was compared to clinical benefit (PD versus other outcome at 6 months).
Secondary Outcomes
- Correlation of FES Uptake With ER Assays(Up to 6 months)
- Number of Participants With Clinical Benefit(Up to 6 months)
- Time to Progression(Up to 6 months)