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

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ClinicalTrials.gov Identifier: NCT04316117
Recruitment Status : Recruiting
First Posted : March 20, 2020
Last Update Posted : May 22, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Tracking Information
First Submitted Date  ICMJE March 18, 2020
First Posted Date  ICMJE March 20, 2020
Last Update Posted Date May 22, 2020
Actual Study Start Date  ICMJE April 2, 2020
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
Performance of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) response criteria as a binary predictor of progression-free survival (PFS) [ Time Frame: Up to 3 years after study registration ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
  • 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 [ Time Frame: Up to 3 years after study registration ]
    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).
  • 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 [ Time Frame: Up to 3 years after study registration ]
    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).
  • 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 [ Time Frame: Up to 3 years after study registration ]
    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).
  • Ability of FDG-PET/CT metrics to predict PFS in patients with BD MBC [ Time Frame: Up to 3 years after study registration ]
    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.
  • Ability of FDG-PET/CT metrics to predict time to SRE in patients with BD MBC [ Time Frame: Up to 3 years after study registration ]
    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.
  • Ability of FDG-PET/CT metrics to predict OS in patients with BD MBC [ Time Frame: Up to 3 years after study registration ]
    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.
  • Utility of FDG-PET/CT to identify disease progression by identification of new lesions not identified by standard CT and bone scan [ Time Frame: Up to 3 years after study registration ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 18, 2020)
  • Defining of criteria for selection of FDG-avid bone lesions for analysis based on thresholds for SULpeak or SUVmax [ Time Frame: Up to 3 years after study registration ]
    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.
  • Exploration of alternative methods for measuring metabolic response with FDG-PET/CT to predict clinical endpoints in patients with BD MBC [ Time Frame: Up to 3 years after study registration ]
    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.
  • Automated image analysis of FDG-PET/CT [ Time Frame: Up to 3 years after study registration ]
    Will evaluate automated image analysis of FDG-PET/CT by AutoPERCIST.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Using FDG-PET/CT to Assess Response of Bone-Dominant Metastatic Breast Cancer, FEATURE Study
Official Title  ICMJE FDG PET to Assess Therapeutic Response in Patients With Bone-Dominant Metastatic Breast Cancer, FEATURE
Brief 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Systemic therapy
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Anatomic Stage IV Breast Cancer AJCC v8
  • Hormone Receptor Positive Breast Carcinoma
  • Metastatic Breast Carcinoma
  • Prognostic Stage IV Breast Cancer AJCC v8
Intervention  ICMJE
  • Procedure: Computed Tomography
    Undergo PET/CT
    Other Names:
    • CAT
    • CAT scan
    • computerized axial tomography
    • Computerized Tomography
    • CT
    • CT scan
    • tomography
  • Other: Fludeoxyglucose F-18
    Given IV
    Other Names:
    • 18FDG
    • FDG
    • Fludeoxyglucose (18F)
    • fludeoxyglucose F 18
    • Fludeoxyglucose F18
    • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
    • Fluorodeoxyglucose F18
  • Procedure: Positron Emission Tomography
    Undergo PET/CT
    Other Names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • positron emission tomography scan
    • Positron-Emission Tomography
    • proton magnetic resonance spectroscopic imaging
Study Arms  ICMJE Experimental: Diagnostic (FDG-PET/CT)
Patients receive FDG 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.
Interventions:
  • Procedure: Computed Tomography
  • Other: Fludeoxyglucose F-18
  • Procedure: Positron Emission Tomography
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 18, 2020)
134
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2021
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04316117
Other Study ID Numbers  ICMJE EA1183
NCI-2020-00210 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA1183 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA1183 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
Study Sponsor  ICMJE ECOG-ACRIN Cancer Research Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Jennifer M Specht ECOG-ACRIN Cancer Research Group
PRS Account Eastern Cooperative Oncology Group
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP