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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2022-00238 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 21623 | Other Identifier | City of Hope Medical Center | |
| P30CA033572 | U.S. NIH Grant/Contract | View source |
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PI withdrawn
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This clinical trial attempts to understand the differences between two chemotherapy drugs, ribociclib and palbociclib, and how they fight cancer. This study looks at tissue and blood characteristics of patients receiving these therapies in the hopes to develop a way to predict which medication would provide the most benefit to an individual patient.
PRIMARY OBJECTIVE:
I. To identify predictive immune biomarkers and mechanisms of response to ribociclib or palbociclib in advanced, hormone receptor positive breast cancer patients.
SECONDARY OBJECTIVES:
I. Identify changes in antigen presentation machinery and costimulatory molecules on circulating myeloid cells as a result of ribociclib or palbociclib treatment.
II. Characterize the dynamic remodeling of circulating myeloid cell composition that occur as a result of ribociclib or palbociclib treatment.
III. Characterize acquired immune tumor microenvironment features of resistance in patients that progress while undergoing ribociclib or palbociclib treatment.
EXPLORATORY OBJECTIVE:
I. To study the association between immune biomarkers and clinical response.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
PROSPECTIVE COHORT: Patients receive standard of care (SOC) treatment consisting of ribociclib or palbociclib plus aromatase inhibitor (AI). Patients undergo biopsy of tumor tissue at baseline and post-treatment. Patients also undergo collection of blood samples at baseline, on day 1 of SOC treatment cycles 2, 4, and 6, every 6 cycles thereafter, and at post-treatment.
RETROSPECTIVE COHORT: Patients' tumor tissue collected during previous SOC treatment (ribociclib or palbociclib plus AI) is used for analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prospective cohort (SOC treatment, biopsy, blood collection) | Experimental | Patients receive SOC treatment consisting of ribociclib or palbociclib plus AI. Patients undergo biopsy of tumor tissue at baseline and post-treatment. Patients also undergo collection of blood samples at baseline, on day 1 of SOC treatment cycles 2, 4, and 6, every 6 cycles thereafter, and at post-treatment. |
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| Retrospective cohort | Experimental | Patients' tumor tissue collected during previous SOC treatment (ribociclib or palbociclib plus AI) is used for analysis. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Best Practice | Other | Given standard of care ribociclib + AI or palbociclib + AI |
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| Measure | Description | Time Frame |
|---|---|---|
| Immune cell frequency (relative abundance, cells per parental cell) | Will be assessed by high dimensional flow cytometry. One-way analysis of variance (ANOVAs) and non-parametric Kruskal-Wallis tests will be used to compare relative abundances across patient groups and over the course of therapy. Wilcoxon rank-sum test will be used to examine the association between each biomarker of each sample collection and pathological response as appropriate. Odds ratios and 95% conference intervals will be calculated to measure strength of associations. P-values < 0.05 will be considered statistically significant. No adjustment for multiple comparisons will be used in view of the exploratory nature of this analysis. | From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Single-cell gene expression | Expected to identify > 30 myeloid and lymphocyte immune subsets. Gene expression relating to maturation and function will be focused on in myeloid subsets especially. Will be assessed by single-cell ribonucleic acid (RNA) sequencing. Immune cell type identification and gene expression patterns will be identified by unsupervised clustering and non-linear dimensionality reduction approaches. Cluster biomarkers will be identified by Seurat for annotating cell types (or functions) for each cell. Within each cluster, will compare the cellular differences in RNA expression across response and non-response cohorts of tumor and peripheral blood mononuclear cell (PBMC) samples by built-in MAST package and Wilcoxon rank-sum test, respectively. Single-cell trajectory analysis for single-cell RNA expression profile will be implemented by Monocle 3 to discover the transitions of cell states in the blood over the course of treatment. |
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Inclusion Criteria:
Exclusion Criteria:
Patient received prior treatment with any CDK4/6 inhibitor
Prior treatment with any chemotherapy for metastatic disease
Patient is cognitively impaired
Lung or bone metastasis only (not accessible by ultrasound guided biopsy)
Patients with central nervous system (CNS) involvement unless they meet ALL the following criteria:
Untreated brain metastases (e.g., lesions < 1cm) not needing immediate local therapy
Previously treated brain metastases not needing immediate local therapy
At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug:
Patient is currently receiving or has received systemic corticosteroids =< 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment
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| Name | Affiliation | Role |
|---|---|---|
| Yuan Yuan | City of Hope Medical Center | Principal Investigator |
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| Biopsy | Procedure | Undergo biopsy of tumor tissue |
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| Biospecimen Collection | Procedure | Undergo blood sample collection |
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| Laboratory Biomarker Analysis | Other | Undergo analysis of previously collected tumor tissue |
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| From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| Psuedotime gene trajectory | Will be assessed by multiplex immunofluorescence. Cell classifications based on panel design will be created for all cell objects detected in whole slide images of tissues. Tissue segmentation for tumor and stroma areas will be created. Densities of cell classifications within whole tissue, tumor areas, and stroma areas will be calculated. Neighborhood analysis, based off 25micron radius, will be examined using Cytomap to identify patterns of cell-cell interactions within tissues. All quantitative image analysis data between pre-treatment and post-treatment samples will be compared in the context of clinical response to CDK4/6i by Wilcoxon rank-sum tests. | From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| Cells per mm^2 tissue | Will be assessed by multiplex immunofluorescence. Cell classifications based on panel design will be created for all cell objects detected in whole slide images of tissues. Tissue segmentation for tumor and stroma areas will be created. Densities of cell classifications within whole tissue, tumor areas, and stroma areas will be calculated. Neighborhood analysis, based off 25micron radius, will be examined using Cytomap to identify patterns of cell-cell interactions within tissues. All quantitative image analysis data between pre-treatment and post-treatment samples will be compared in the context of clinical response to CDK4/6i by Wilcoxon rank-sum tests. | From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| Cells per mm^2 cancer island | Will be assessed by multiplex immunofluorescence. Cell classifications based on panel design will be created for all cell objects detected in whole slide images of tissues. Tissue segmentation for tumor and stroma areas will be created. Densities of cell classifications within whole tissue, tumor areas, and stroma areas will be calculated. Neighborhood analysis, based off 25micron radius, will be examined using Cytomap to identify patterns of cell-cell interactions within tissues. All quantitative image analysis data between pre-treatment and post-treatment samples will be compared in the context of clinical response to CDK4/6i by Wilcoxon rank-sum tests. | From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| Average cell-cell distances (within neighborhood) | Will be assessed by multiplex immunofluorescence. Cell classifications based on panel design will be created for all cell objects detected in whole slide images of tissues. Tissue segmentation for tumor and stroma areas will be created. Densities of cell classifications within whole tissue, tumor areas, and stroma areas will be calculated. Neighborhood analysis, based off 25micron radius, will be examined using Cytomap to identify patterns of cell-cell interactions within tissues. All quantitative image analysis data between pre-treatment and post-treatment samples will be compared in the context of clinical response to CDK4/6i by Wilcoxon rank-sum tests. | From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| Cells per mm^2 stroma | Will be assessed by multiplex immunofluorescence. Cell classifications based on panel design will be created for all cell objects detected in whole slide images of tissues. Tissue segmentation for tumor and stroma areas will be created. Densities of cell classifications within whole tissue, tumor areas, and stroma areas will be calculated. Neighborhood analysis, based off 25micron radius, will be examined using Cytomap to identify patterns of cell-cell interactions within tissues. All quantitative image analysis data between pre-treatment and post-treatment samples will be compared in the context of clinical response to CDK4/6i by Wilcoxon rank-sum tests. | From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| Number of core cells with cell(s) in neighborhood | Will be assessed by multiplex immunofluorescence. Cell classifications based on panel design will be created for all cell objects detected in whole slide images of tissues. Tissue segmentation for tumor and stroma areas will be created. Densities of cell classifications within whole tissue, tumor areas, and stroma areas will be calculated. Neighborhood analysis, based off 25micron radius, will be examined using Cytomap to identify patterns of cell-cell interactions within tissues. All quantitative image analysis data between pre-treatment and post-treatment samples will be compared in the context of clinical response to CDK4/6i by Wilcoxon rank-sum tests. | From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| Number of spatial clusters | Will be assessed by multiplex immunofluorescence. Cell classifications based on panel design will be created for all cell objects detected in whole slide images of tissues. Tissue segmentation for tumor and stroma areas will be created. Densities of cell classifications within whole tissue, tumor areas, and stroma areas will be calculated. Neighborhood analysis, based off 25micron radius, will be examined using Cytomap to identify patterns of cell-cell interactions within tissues. All quantitative image analysis data between pre-treatment and post-treatment samples will be compared in the context of clinical response to CDK4/6i by Wilcoxon rank-sum tests. | From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years |
| ID | Term |
|---|---|
| D017410 | Practice Guidelines as Topic |
| D059039 | Standard of Care |
| D001706 | Biopsy |
| ID | Term |
|---|---|
| D017408 | Guidelines as Topic |
| D011785 | Quality Assurance, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
| D019984 | Quality Indicators, Health Care |
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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