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

Anatomic Stage IV Breast Cancer AJCC v8 Clinical Trial

Official title:

FDG PET to Assess Therapeutic Response in Patients With Bone-Dominant Metastatic Breast Cancer, FEATURE

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04316117
• Other study ID #: EA1183
• Secondary ID: NCI-2020-00210EA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 15, 2020
• Est. completion date: August 31, 2027

Study information

• Verified date: April 2024
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 138
• Est. completion date: August 31, 2027
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance (performance status [PS]) =< 2

• Patients 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

• Patients must have radiologically confirmed bone-dominant (BD) or bone-only (BO) disease

• 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

• Patients must have no contraindication to FDG-PET imaging

• Patients must have one of the following systemic therapies:

• Plan to receive either 1st or 2nd 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 (palbociclib, ribociclib, abemaciclib, everolimus, alpelisib)

• 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

• 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's life expectancy must be estimated at >= 24 weeks

• 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 PET/CT scanner qualification procedures and received ECOG-ACRIN PET/CT scanner approval

• Patients must complete the baseline (T0) FDG-PET within 28 days prior to registration or within 28 days after registration

• 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 the following tests are exempt:

• Pregnancy testing documentation prior to FDG-PET (T0 time point)

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 currently participating in or have participated in a study of 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

• Women 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, women who are breastfeeding are also excluded from this study. All females of childbearing potential must have a blood test or urine study within 7 days prior to FDG-PET/CT to rule out pregnancy. Patients are excluded from this if baseline FDG-PET/CT scan met study parameters and was completed within 28 days of study registration

Related Conditions & MeSH terms

• Anatomic Stage IV Breast Cancer AJCC v8
• Breast Neoplasms
• Carcinoma
• Hormone Receptor Positive Breast Carcinoma
• Metastatic Breast Carcinoma
• Prognostic Stage IV Breast Cancer AJCC v8

Intervention

Procedure:
• Computed Tomography
Undergo PET/CT

Other:
• Fludeoxyglucose F-18
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET/CT

Locations

Country	Name	City	State
Ireland	Cork University Hospital	Cork
Puerto Rico	Cancer Center-Metro Medical Center Bayamon	Bayamon
Puerto Rico	Doctors Cancer Center	Manati
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	GenesisCare USA - Aventura FP	Aventura	Florida
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UPMC Western Maryland	Cumberland	Maryland
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Bayhealth Hospital Kent Campus	Dover	Delaware
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Kettering Medical Center	Kettering	Ohio
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Morristown Medical Center	Morristown	New Jersey
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Mount Sinai Hospital	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Ireland,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Defining of criteria for selection of FDG-avid bone lesions for analysis based on thresholds for SULpeak or SUVmax	Will vary the threshold for inclusion in the PERCIST criteria to get optimum performance. To reduce the over-optimism, will apply the statistical technique of 5-fold cross-validation in the threshold discovery and subsequent performance assessment.	Up to 3 years after study registration
Other	Exploration of alternative methods for measuring metabolic response with FDG-PET/CT to predict clinical endpoints in patients with BD MBC	Will collaborate with National Cancer Institute Quantitative Imaging Network to explore alternative methods for measuring metabolic response with FDG-PET/CT scans. Will then implement Kaplan Meier survival curve (and log-rank test) or multivariable Cox proportional hazard model in the analyses of associations with PFS, time to SRE, or OS.	Up to 3 years after study registration
Other	Automated image analysis of FDG-PET/CT	Will evaluate automated image analysis of FDG-PET/CT by AutoPERCIST.	Up to 3 years after study registration
Primary	Performance of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) response criteria as a binary predictor of progression-free survival (PFS)	Will evaluate the performance of FDG-PET/CT response criteria (modified PET Response Criteria in Solid Tumors complete, partial and stable metabolic disease versus progressive metabolic disease) as a binary predictor of PFS in patients with bone-dominant (BD) metastatic breast cancer (MBC) treated with systemic therapy.	Up to 3 years after study registration
Secondary	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	Will keep the multiple categories of FDG-PET/CT modified PERCIST criteria and test the PFS differences across them using the Kaplan-Meier survival curve and the corresponding log-rank test. The multivariable Cox proportional hazard model will be also fitted with the adjustment of the same set of confounders (e.g., age, line of therapy - early line treatment versus late line treatment, type of therapy - endocrine therapy versus chemotherapy). Since the categories of FDG-PET/CT modified PERCIST criteria are ordered, will also apply the method of C-statistics to evaluate the performance after quantifying the criteria (i.e., 1-complete response, 2-partial response, 3-stable, 4-metabolic progression).	Up to 3 years after study registration
Secondary	Ability of FDG-PET/CT modified PERCIST criteria (complete, partial, and stable vs progressive metabolic disease) to predict time to skeletal related events (SRE) in patients with BD MBC	Will keep the multiple categories of FDG-PET/CT modified PERCIST criteria and test the time to SRE differences across them using the Kaplan-Meier survival curve and the corresponding log-rank test. The multivariable Cox proportional hazard model will be also fitted with the adjustment of the same set of confounders (e.g., age, line of therapy - early line treatment versus late line treatment, type of therapy - endocrine therapy versus chemotherapy). Since the categories of FDG-PET/CT modified PERCIST criteria are ordered, will also apply the method of C-statistics to evaluate the performance after quantifying the criteria (i.e., 1-complete response, 2-partial response, 3-stable, 4-metabolic progression).	Up to 3 years after study registration
Secondary	Ability of FDG-PET/CT modified PERCIST criteria (complete, partial, and stable vs progressive metabolic disease) to predict overall survival (OS) in patients with BD MBC	Will keep the multiple categories of FDG-PET/CT modified PERCIST criteria and test the OS differences across them using the Kaplan-Meier survival curve and the corresponding log-rank test. The multivariable Cox proportional hazard model will be also fitted with the adjustment of the same set of confounders (e.g., age, line of therapy - early line treatment versus late line treatment, type of therapy - endocrine therapy versus chemotherapy). Since the categories of FDG-PET/CT modified PERCIST criteria are ordered, will also apply the method of C-statistics to evaluate the performance after quantifying the criteria (i.e., 1-complete response, 2-partial response, 3-stable, 4-metabolic progression).	Up to 3 years after study registration
Secondary	Ability of FDG-PET/CT metrics to predict PFS in patients with BD MBC	For each participant, will collect up to 5 lesions from FDG-PET/CT scans and calculate the percent change in peak standardized uptake value corrected for lean body mass (SULpeak), maximum standardized uptake value corrected for body weight (SUVmax) from T0 to T1 scans. Multivariable Cox proportional hazard models will be used to model the ability of these changes to predict PFS. The analysis will first be conducted on the index lesion (i.e., associating the change of SUVpeak or SUVmax for the index lesion with outcomes), and then be applied to the average change of up to 5 lesions (i.e., associating the average change of SUVpeak or SUVmax from all detected lesions with outcomes). The C-statistics will be used to measure the performance.	Up to 3 years after study registration
Secondary	Ability of FDG-PET/CT metrics to predict time to SRE in patients with BD MBC	For each participant, will collect up to 5 lesions from FDG-PET/CT scans and calculate the percent change in SULpeak, SUVmax from T0 to T1 scans. Multivariable Cox proportional hazard models will be used to model the ability of these changes to predict time to SRE. The analysis will first be conducted on the index lesion (i.e., associating the change of SUVpeak or SUVmax for the index lesion with outcomes), and then be applied to the average change of up to 5 lesions (i.e., associating the average change of SUVpeak or SUVmax from all detected lesions with outcomes). The C-statistics will be used to measure the performance.	Up to 3 years after study registration
Secondary	Ability of FDG-PET/CT metrics to predict OS in patients with BD MBC	For each participant, will collect up to 5 lesions from FDG-PET/CT scans and calculate the percent change in SULpeak, SUVmax from T0 to T1 scans. Multivariable Cox proportional hazard models will be used to model the ability of these changes to predict OS. The analysis will first be conducted on the index lesion (i.e., associating the change of SUVpeak or SUVmax for the index lesion with outcomes), and then be applied to the average change of up to 5 lesions (i.e., associating the average change of SUVpeak or SUVmax from all detected lesions with outcomes). The C-statistics will be used to measure the performance.	Up to 3 years after study registration
Secondary	Utility of FDG-PET/CT to identify disease progression by identification of new lesions not identified by standard CT and bone scan	For the cases where progression is documented in the study, will record and tabulate the number of new lesions uniquely identified by the 12-week FDG-PET/CT research scan.	Up to 3 years after study registration