Utilizing Multiomic Advanced Diagnostics to Identify CDK 4/6 Inhibitor Response Predictors and a Post-treatment Multiomic Signature for Patients With ER+/HER2- Metastatic Breast Cancer

June 30, 2020 updated by: Side-Out Foundation
This is an open-label, multicenter study in patients with metastatic breast cancer who are candidates for standard first line treatment with palbociclib or ribociclib plus endocrine therapy. To be eligible, patients must have received no prior chemotherapeutic or hormonal regimen for metastatic disease. However, patients may still be considered eligible if they have already started treatment with endocrine therapy (an aromatase inhibitor or fulvestrant) plus palbociclib or ribociclib for no longer than 4 weeks prior to study enrollment, as long as they meet all other eligibility criteria. Eligible patients must have had a diagnostic biopsy of the metastatic lesion no more than 4 months prior to study enrollment and with sufficient tissue to complete the proposed biomarker analysis. Patients who develop disease progression within the first 12 months of starting palbociclib or ribociclib plus endocrine therapy will be eligible for an optional additional tissue biopsy at time of disease progression to repeat the analysis at time of disease progression and obtain real-time (10-14-day turn-around) multi-omic data produced under College of American Pathologist (CAP)/Clinical Laboratory Improvement Amendments (CLIA) development and/or compliant practices.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-0113
        • University of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
    • Florida
      • Miami, Florida, United States, 33136
        • UHealth/Sylvester Comprehensive Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Sidney Kimmel Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center Perelman Center for Advanced Medicine
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Women & Infants Hospital of Rhode Island
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease.
  • Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP 2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by immunohistochemistry based on local laboratory results.
  • Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (HER2/CEP17 ratio must be < 2, and HER2 copy number < 6 signals/cell), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards.
  • Must be candidates to receive endocrine therapy and palbociclib or ribociclib as first-line treatment for their advanced disease. Patients will be considered eligible for study enrollment if they have started on treatment with a standard dose and schedule of palbociclib or ribociclib and endocrine therapy (aromatase inhibitor or fulvestrant) as long as they have not started palbociclib or ribociclib treatment for longer than 4 weeks from time of study enrollment, have sufficient tissue to perform the proposed tissue analysis and must meet all other eligibility criteria. Endocrine therapy can be initiated up to 4 weeks prior to starting palbociclib or ribociclib.
  • Patients must have measurable disease by RECIST v.1.1 or bone disease as their only site of disease (with bone lesions confirmed by CT, MRI or bone X-ray).
  • No prior treatment with chemotherapy for a diagnosis of locoregionally recurrent or metastatic breast cancer is allowed.
  • Be ≥ 18 years of age
  • Have an ECOG score of 0-1

  • Postmenopausal women defined as women with:

    • Prior bilateral surgical oophorectomy, or
    • Medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months or follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol blood levels in their respective postmenopausal ranges.
  • Premenopausal women will be considered eligible for study participation if they are receiving medical ovarian suppression with luteinizing hormone-releasing hormone (LHRH) agonists with documented estradiol blood levels in their respective postmenopausal ranges.
  • Archive tumor tissue (obtained from a biopsy or surgical resection of a metastatic lesion done within 4 months from study enrollment) availability is required for patient participation. If the available tissue is insufficient for the required baseline analysis, the patients are given the option to repeat the biopsy for the purpose of study participation as long as they have not already started palbociclib or ribociclib.
  • Understand and provide written informed consent prior to initiation of any study-specific procedures.

Exclusion Criteria:

  • Lack of archive tumor tissue from a biopsy or surgical resection of a metastatic lesion done within 4 months of study enrollment. Patients will be given an option to have a repeated biopsy of a metastatic lesion if they had a diagnostic tumor biopsy intended for use in the current study that was performed more than 4 months prior to analysis, or there is insufficient tissue from the initial biopsy to complete the analysis, as long as they have not started treatment with a CDK 4/6 inhibitor. Otherwise, the patient will be excluded from the study participation.
  • Have symptomatic CNS metastasis. Patients with a history of CNS metastases who have been treated with whole brain irradiation must be stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable does of steroids for ≥ 4 weeks prior to enrollment.
  • Have uncontrolled concurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, psychiatric illness, or situations that would limit compliance with the study requirements or ability to willingly give written informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
OTHER: Single arm
This is a biomarker study analyzing tissue for baseline biomarkers and collecting tissue at progression for further analysis of biomarkers changes after treatment with CDK 4/6 inhibitors and endocrine therapy
Other: biomarker study
This is a biomarker study

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Evaluate baseline phosphorylated RB levels in tumor tissue as a predictive marker of response to palbociclib or ribociclib as first line treatment for ER+/HER2- metastatic breast cancer
Time Frame: 2 years
Establish baseline values in tumor tissue to use as predictive markers
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evaluate baseline biomarkers which are direct substrates of CDK 4/6 or controlled secondarily by CDK 4/6 kinase activity as qualifying predictive markers of response to CDK 4/6 inhibitors as first line treatment for ER+/HER2- metastatic breast cancer
Time Frame: 2 years
Identify CDK 4/6 kinase which are either direct substrates or controlled secondarily by CDK 4/6 activity.
2 years
Evaluate tumor tissue collected at time of disease progression, for post CDK 4/6 inhibitor treatment changes in biomarkers which are either direct substrates of Cyclin Dependent (CDK) 4/6 kinase or controlled secondarily by CDK 4/6 kinase activity.
Time Frame: 2 years
Evaluate tissue collected at progression for changes in CDK 4/6 biomarkers after treatment with CDK 4/6 inhibitors.
2 years
Evaluate tumor tissue collected at time of disease progression for measurement of the activation state signaling pathways that are known markers for endocrine resistance (e.g. AKT-mTOR signaling).
Time Frame: 2 years
Evaluate tissue collected at progression for activation state of signaling pathways that are known markers for endocrine resistance
2 years
Determine frequency when "multi-omic" profiling: proteomic and genomic profiling analysis of patient's tumor yields a target against which there is an FDA-approved agent or therapeutic regimen.
Time Frame: 2 years
Evaluate frequency with which multiomic profiling analysis of patient's tumor identifies a target that can be treated by an FDA-approved agent or regimen
2 years
Determine percent of time multiomic profiling based treatment recommendation is different than treatment selected by the patient's physician once a patient shows progression after first line treatment with palbociclib or ribociclib
Time Frame: 2 years
Evaluate percentage of time when treatment recommendations found with multiomic profiling is different than treatment selected by a patient's physician
2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Perform RPPA based batch analysis of all samples at the end of this study to measure 50-100 protein signaling targets. Protein activation will be correlated with clinical response.
Time Frame: 2 years
The data from this exploratory analysis will help generate hypotheses for future studies.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Side-Out Foundation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Translational Drug Development

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 9, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 9, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 22, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 1, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SO-BCA-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Dietary Supplements

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