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Advanced Breast AdenocarcinomaNCT05244434

Effects of Ribociclib and Palbociclib on Tumor and Blood Characteristics in Patients With Metastatic Breast Cancer

A study testing Best Practice, Biopsy and Biospecimen Collection in people with Advanced Breast Adenocarcinoma and Advanced HER2-Negative Breast Carcinoma, run by City of Hope Medical Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Best Practice, Biopsy and Biospecimen Collection
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
3 Jul 2022to 26 Jan 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histological confirmed breast adenocarcinoma who meet the following criteria:
  • Age: >= 18 years and are post-menopausal
  • Estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 (HER2) negative breast cancer patients who prospectively may undergo evaluation for Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), ribociclib or palbociclib, as part of first-line therapy. Retrospective cohorts will be built to include either ribociclib or palbociclib treated patients with known clinical outcome
  • During routine standard of care procedure, tumor that is accessible for ultrasound guided biopsy (from breast, lymph node, subcutaneous tumor, or selected liver metastasis per treating physician's discretion) or skin punch biopsy (for dermal metastasis) will be collected
  • Available tumor tissue or planning on biopsy prior to initiation of CDK4/6i treatment
  • Available tumor tissue or planning on biopsy at time of progression, prior to initiating subsequent therapy
  • Willing to provide consent for extra tissue and blood samples

Who cannot join

  • 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
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  • 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 stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
  • 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:
  • Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
  • That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
  • Herbal preparations/medications, dietary supplements
  • Warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), newer anticoagulation agents such as direct factor Xa inhibitors, or fondaparinux is allowed
  • 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
  • The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)

About this study

Official title: Comparative Effects of Ribociclib and Palbociclib on Circulating and Tumor Infiltrating Myeloid Cells in Metastatic Breast Cancer Patients

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To identify predictive immune biomarkers and mechanisms of response to ribociclib or palbociclib in advanced, hormone receptor positive breast cancer patients.

SECONDARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Best Practice, Biopsy, Biospecimen Collection, Laboratory Biomarker Analysis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Best PracticeOther

    Also called standard of care, standard therapy

    Given standard of care ribociclib + AI or palbociclib + AI

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy of tumor tissue

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected

    Undergo blood sample collection

  • Laboratory Biomarker AnalysisOther

    Undergo analysis of previously collected tumor tissue

Study groups in NCT05244434
Study groupRoleWhat they receive
Prospective cohort (SOC treatment, biopsy, blood collection)ExperimentalPatients 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.
Receives: Other: Best Practice; Procedure: Biopsy; Procedure: Biospecimen Collection; Other: Laboratory Biomarker Analysis
Retrospective cohortExperimentalPatients' tumor tissue collected during previous SOC treatment (ribociclib or palbociclib plus AI) is used for analysis.
Receives: Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

Secondary outcomes (8)

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

  5. 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.

    Measured: 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

  6. 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.

    Measured: 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

  7. 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.

    Measured: 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

  8. 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.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2022
  2. Study start3 Jul 2022 (estimated)
  3. Primary completion26 Jan 2023 (estimated)
  4. Study completion26 Jan 2023 (estimated)

Why it stopped: PI withdrawn

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05244434
Sponsor's protocol ID
21623
Other IDs
NCI-2022-00238, 21623, P30CA033572
Status last verified
Jun 2022
First submitted
8 Feb 2022
Last updated
9 Jun 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A study testing Best Practice, Biopsy and Biospecimen Collection in people with Advanced Breast Adenocarcinoma and Advanced HER2-Negative Breast Carcinoma, run by City of Hope Medical Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 9 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immune cell frequency (relative abundance, cells per parental cell) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05244434.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2022.

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