The Resistance and Immune Response to Palbociclib in Breast Cancer

January 15, 2018 updated by: Yeon Hee Park, Samsung Medical Center

Prospective Longitudinal Biomarker Study of Acquired Resistance and Immune Response to Palbociclib in Breast Cancer

The investigators propose to conduct a biomarker and molecular profiling study in longitudinally paired tumor biopsies and serum from patients with Hormone Receptor positive (HR+) metastatic Breast Cancer (BC) treated with Palbociclib in combination with endocrine therapies.

Study Overview

Status

Status

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

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.

Detailed Description

The investigators propose to conduct a biomarker and molecular profiling study in longitudinally paired tumor biopsies and serum from patients with Hormone Receptor positive (HR+) metastatic Breast Cancer (BC) treated with Palbociclib(Palbo) in combination with endocrine therapies.

The investigators plan to obtain tumor biopsy and blood samples, taken at both pre-treatment and post-progression, from 40 patients who develop acquired resistance to Palbo + endocrine combination treatment. All assays will be conducted in parallel on both pre and post-treatment samples to identify differences that may account for acquired resistance. Cyclin E1 and E2 levels will be assessed by IHC on tumor biopsies. Neuregulin-1 levels will be assessed by ELISA assay on serum. Tumor biopsies will be further profiled using whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-Seq). Matched blood samples will be subject to WES to facilitate somatic mutation detection. Paired tumor biopsies will undergo immunohistochemistry (IHC) analysis of TIL markers to assess Palbo-induced changes. Finally, we will apply the in-house circulating tumor DNA (ctDNA) assay, which employs a custom-designed panel for studying Palbo acquired resistance, towards the analysis of 40 pairs of plasma samples. The custom ctDNA panel will be extended to include additional mutations identified from this study that confer acquired resistance.

To further evaluate the effects of Palbo treatment on intratumoral TILs, the investigators plan to acquire paired tumor biopsy and matched blood samples, at baseline and two time points (6 weeks, 12 weeks) during the course of Palbo treatment, from 20 patients. And they will select metastatic BC patients who exhibit stable diseases (SD) in response to Palbo for tumor biopsies, prior to knowledge of whether post-progression biopsy would be available. Tumor biopsies will be subject to WES, RNA-Seq and IHC analyses. Further, the investigators plan to quantify the abundance of immune cell sub-populations in the matched blood samples using flow cytometry (FACS) to assess Palbo treatment effects on systematic immunity.

While on-treatment samples can be collected after 6 weeks and 12 weeks of initiating Palbo treatment, it takes about 18 months on average for initially treated patients with late stage HR+ breast cancers to develop acquired resistance. Only an estimated 40% of relapsed cases will have successful biopsies due to a lack of consent or difficult-to-operate biopsies such as bone-only metastases. Hence, the investigators plan to bank pre-treatment biopsies and blood samples from about 100 patients by Q2 2018 in order to collect 40 post-progression biopsies as matched pairs within the 2-year time frame. FFPE slides will be made from all tumor biopsies, including the 100 cases at baseline, and subject to H&E staining. The investigators will detect and quantify TILs through machine learning and digital imaging analysis of the H&E data.

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 (Anticipated)

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.
100

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

  • Korea, Republic of
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center
        • Contact:
          • Yeon Hee Park, MD, Ph.D

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

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Hormone receptor positive, metastatic breast cancer
  • Treated by palbociclib with endocrine therapy

Exclusion Criteria:

  • Hormone receptor negative breast cancer
  • Treated without palbociclib
  • Refuse and withdrawal to this study

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: BASIC_SCIENCE
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

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
Biomarker of palbociclib in metastatic breast cancer
Time Frame: 24.8 months (median progression free survival in palbociclib plus letrozole treatment (according to PALOMA-2 trial)
Biomarker of acquired resistance and immune response to palbociclib in metastatic breast cancer from whole exome sequencing, RNASeq, circulating tumor DNA and flow cytometry.
24.8 months (median progression free survival in palbociclib plus letrozole treatment (according to PALOMA-2 trial)

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.
Samsung Medical Center

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.
October 24, 2017

Primary Completion (ANTICIPATED)

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.
October 31, 2020

Study Completion (ANTICIPATED)

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.
October 31, 2022

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).
December 11, 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.
January 15, 2018

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.
January 17, 2018

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.
January 17, 2018

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.
January 15, 2018

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.
January 1, 2018

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.
  • 2017-07-049

Drug and device information, study documents

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

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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