Using FDG-PET / CT to Assess Response of Bone-Dominant Metastatic Breast Cancer, FEATURE Study

This phase II trial studies how well FDG-PET / CT works in assessing the response of patients with breast cancer that has spread to the bones or mostly to the bones (bone-dominant metastatic breast cancer). Diagnostic procedures, such as FDG-PET / CT, may work better in measuring breast cancer activity before and after treatment compared to other standard imaging tests.

Inclusion Criteria

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance (performance status [PS]) =< 2
• Patient with histologically confirmed metastatic breast cancer by local assessment that is hormone receptor positive by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and with known HER2 status. * NOTE: Confirmation can be documented via a report from a metastatic biopsy; a separate biopsy does not need to be completed. If there is no report from a metastatic biopsy, the pathology report from primary breast cancer diagnosis documenting breast cancer along with estrogen receptor (ER), progesterone receptor (PR) and HER2 status can be utilized
• Patient must have radiologically confirmed bone-dominant (BD) or bone-only (BO) disease confirmed by scans obtained within 60 days prior to registration * BD defined as disease involving bone with or without limited measurable metastases by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, with >= 1 non-irradiated bone metastasis on bone scintigraphy ** NOTE: Limited measurable metastases includes lymph nodes and the soft tissue components of lytic or mixed lytic/blastic bone metastases. Any number of lymph nodes < 3 cm and up to 2 lymph nodes > 3 cm will be allowed. Up to 5 measurable soft tissue components of lytic or mixed mytic/blastic bone metastases will be allowed * BO defined as detectable disease confined within the bone (any site, any number of lesions). Diagnosis requires abnormalities identified by imaging (bone scan, CT +/- PET +/- magnetic resonance imaging [MRI]) with no other sites of metastases identified and with >= 1 non-irradiated bone metastasis on bone scintigraphy
• Patient must have no contraindication to FDG-PET imaging which includes glucose values > 200 mg/dL and severe claustrophobia
• Patient must have one of the following systemic therapies: * Plan to receive either 1st, 2nd or 3rd line endocrine therapy for metastatic breast cancer. Endocrine therapy may include selective estrogen receptor modulators (SERMs), aromatase inhibitors, and/or fulvestrant that may be combined with Food and Drug Administration (FDA)-approved biologic agents (examples include CDK 4/6 inhibitors mTOR inhibitors and parp inhibitors for BRCA germ mutation) * Plan to receive chemotherapy per National Comprehensive Cancer Network (NCCN) or institutional standard. Use of colony stimulating growth factor must be suspended for >= 14 days prior to FDG-PET/CT scans at baseline and 12-weeks * Plan to receive HER2-targeted therapy per ASCO, NCCN, and/or institutional guidelines as indicated for patients with HER2 positive disease. When HER2-targeted therapy is used with chemotherapy, use of colony stimulating growth factors is NOT expected or should be suspended for a minimum of 2 weeks, but preferably for at least 3 weeks prior to the required FDG-PET/CT scan time points * NOTE: The use of bone-stabilizing agents (bisphosphonates or denosumab) is permitted
• Patient must meet institutional guidelines for renal function for MRI and CT scanning
• Patient must have life expectancy estimated at >= 24 weeks
• Patient must be 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 PET/CT scanner qualification procedures and received ECOG-ACRIN PET/CT scanner approval
• Patient must complete the baseline (T0) FDG-PET within 28 days after registration. A FDG-PET/CT completed prior to registration may be used if all imaging parameters have been met and patient is able to start treatment within 21 days after completion of FDG/PET CT * For patients completing the baseline (T0) FDG-PET AFTER registration all parameters must be met * For patients who completed the baseline (T0) FDG-PET PRIOR to registration all parameters must be met with the following exemption: ** Pregnancy testing documentation prior to FDG-PET (T0 time point) for patients of childbearing potential will not be required

Exclusion Criteria

• Patients with RECIST 1.1 measurable lesions in viscera, active central nervous system (CNS), leptomeningeal carcinomatous or pleural or peritoneal disease will not be eligible. Patients with prior CNS metastases treated with radiation or resection and without evidence of clinical or radiographic progression within 28 days of registration are eligible
• Patients who have received greater than 3 lines of cytotoxic chemotherapy for metastatic breast cancer are not eligible
• Patients using an investigational agent or using an investigational device within 3 weeks of study registration are not eligible
• Patients with known additional malignancy that is progressing or requires active treatment are not eligible. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Patient must not be pregnant because FDG is a radiopharmaceutical with the potential for teratogenic effects and PET/CT involves additional radiation exposure. In addition, because of radiation exposure to a nursing infant from FDG, patients who are breastfeeding are also excluded from this study. All patients of childbearing potential must have a blood test or urine study within 7 days prior to FDG-PET/CT to rule out pregnancy

PRIMARY OBJECTIVE:

I. Evaluate the performance of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) response criteria (modified PET Response Criteria in Solid Tumors [PERCIST] complete, partial and stable metabolic disease versus progressive metabolic disease) as a binary predictor of progression-free survival (PFS) in patients with bone-dominant (BD) metastatic breast cancer (MBC) treated with systemic therapy.

SECONDARY OBJECTIVES:

I. Evaluate the ability of FDG-PET/CT modified PERCIST criteria (complete versus [vs] partial vs stable vs metabolic progression) to independently predict PFS in patients with BD MBC.

II. Evaluate the ability of FDG-PET/CT modified PERCIST criteria (complete, partial, and stable versus progressive metabolic disease) to predict time to skeletal related events (SRE) and overall survival (OS) in patients with BD MBC.

III. Evaluate the ability of FDG-PET/CT metrics (percent change in peak standardized uptake value corrected for lean body mass (SULpeak), maximum standardized uptake value corrected for body weight (SUVmax) as continuous variables in index or up to 5 lesions) to predict PFS, time to SRE and OS in patients with BD MBC.

IV. Assess the utility of FDG-PET/CT to identify disease progression by identification of new lesions not identified by standard CT and bone scan.

EXPLORATORY OBJECTIVES:

I. Define criteria for selection of FDG-avid bone lesions for analysis based on thresholds for SULpeak or SUVmax.

II. In collaboration with National Cancer Institute (NCI) Quantitative Imaging Network (QIN), explore alternative methods for measuring metabolic response with FDG-PET/CT (e.g., total lesion glycolysis, quantitative total bone imaging, MD Anderson bone criteria, and radiomics) to predict clinical endpoints in patients with BD MBC.

III. Evaluate automated image analysis of FDG-PET/CT by AutoPERCIST.

IV. Assess the ability of qualitative and quantitative changes in serial circulating tumor deoxyribonucleic acid (ctDNA) measures to predict PFS, tSRE, and overall survival in patients enrolled in EA1183.

OUTLINE:

Patients receive FDG intravenously (IV) and undergo PET/CT scan over 15-30 minutes at baseline (within 21 days before start of standard systemic treatment) and at 12 weeks after start of standard systemic treatment in the absence of unacceptable toxicity.

After completion of study, patients are followed up periodically for up to 3 years after study registration.

Trial Phase Phase II

Trial Type Diagnostic

Lead Organization
ECOG-ACRIN Cancer Research Group

Principal Investigator
Jennifer Marie Specht

• Primary ID EA1183
• Secondary IDs NCI-2020-00210
• Clinicaltrials.gov ID NCT04316117