Pembrolizumab and Exemestane/ Leuprolide in Premenopausal HR+/ HER2- Locally Advanced or Metastatic Breast Cancer (PEER)

February 20, 2023 updated by: National Taiwan University Hospital

A Pilot Study of Pembrolizumab and Exemestane/ Leuprolide in Premenopausal Hormone Receptor Positive/ HER2 Negative Locally Advanced or Metastatic Breast Cancer

This is an open-label, single-arm, multicenter, pilot study of pembrolizumab, exemestane, and leuprolide for subjects being resistant for front-line hormonal therapy for inoperable locally advanced or metastatic hormonal receptor positive (HR+)/ Human epidermal growth factor receptor 2 (HER2) negative breast cancer. All the patients will be included in the final tolerability and preliminary efficacy analysis. The efficacy objectives including PFS, overall response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR). Adverse effects will be recorded according to CTCAE v4.0.

Study Overview

Status

Status

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

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.
16

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.
  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Yen-Shen Lu, MD, PhD
  • Phone Number: +886-2-23123456
  • Email: yslu@ntu.edu.tw

Study Locations

  • Taiwan
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital

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

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Be a female adult aged more than 20-year-old at the time of informed consent.
  2. Have histologically confirmed ER positive (defined as ≥1%) and/ or PR positive (defined as ≥1%) breast cancer.
  3. Have histologically confirmed HER2-negative breast cancer as defined by IHC ≤ 2+, and/or FISH negative.
  4. Have radiological or objective evidence of inoperable locally advanced or metastatic breast cancer.

  5. Be premenopausal or peri-menopausal. Premenopausal or peri-menopausal status is defined as below:

    • Last menstrual period within the last 12 months OR
    • With a plasma estradiol ≥10pg/ml and FSH ≤40IU/L

  6. Be resistant to front line hormonal therapy, as defined as one of the following criteria:

    • Have become inoperable locally advanced or metastatic disease within one year of adjuvant hormonal therapy.
    • Fail at least 2 line of prior hormonal therapy for locally advanced or metastatic breast cancer.
    • Have history of disease progressed within 6 months during 1st line hormone therapy for locally advanced or metastatic disease.
  7. Prior exemestane usage is allowed, but the patient number is limited to ≤10 patients.
  8. Have archival primary tumor specimen from diagnosis.
  9. Have metastatic tumor specimen before enrollment.
  10. Have measurable disease as per RECIST 1.1 or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
  11. Have ECOG performance status 0 or 1 assessed within 10 days of treatment initiation.
  12. Have adequate bone marrow and organ function.
  13. For women of childbearing potential must have a negative serum beta-hCG or urine pregnancy test obtained within 3 days before starting treatment.
  14. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section - Contraception, for the course of the study through 120 days after the last dose of study medication.
  15. Be able to comply with study procedures and sign an informed consent.

Exclusion Criteria:

  1. Is currently participating in an investigational agent study.
  2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment. Physiological steroid replacement is allowed.
  3. Has had chemotherapy within 2 weeks prior to the first dose of study treatment or has not recovered from side effects (i.e. Grade 1 at baseline) except alopecia related to prior therapy.
  4. Is a hepatitis B or C carrier.
  5. Has concurrent malignancy other than non-melanoma skin cancer.
  6. Is not able to undergo metastatic tumor biopsy.
  7. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  8. Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  9. Has an active infection requiring systemic therapy.
  10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or has previously participated in Merck pembrolizumab clinical trials.
  13. Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
  14. Is lactating, pregnant, or unwilling to employ birth control methods during the 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: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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.
Experimental: Pembrolizumab/ Exemestane/ Leuprolide
Dose level 1 (Pembrolizumab 150 mg IV Q2W); Dose level -1 (Pembrolizumab 100 mg IV Q2W); Dose level -2 (Pembrolizumab 50 mg IV Q2W) Combination with Exemestane 25 mg PO QD, and Leuprolide 3.75 mg SC Q4W
Drug: Pembrolizumab/ Exemestane/ Leuprolide
Dose level 1 (Pembrolizumab 150 mg IV Q2W); Dose level -1 (Pembrolizumab 100 mg IV Q2W); Dose level -2 (Pembrolizumab 50 mg IV Q2W) Combination with Exemestane 25 mg PO QD, and Leuprolide 3.75 mg SC Q4W

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
The PFS rate at 8 months
Time Frame: 28 months
To estimate the efficacy of the combination of pembrolizumab and exemestane/ leuprolide in premenopausal with hormone receptor positive/ HER2 negative locally advanced or metastatic breast cancer patients, as defined by PFS rate at 8 months.
28 months

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
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 28 months
28 months
The PFS based on RECIST 1.1
Time Frame: 28 months
28 months
The overall response rate (ORR) based on RECIST 1.1
Time Frame: 28 months
28 months
The clinical benefit rate (CBR) based on RECIST 1.1
Time Frame: 28 months
28 months
The duration of overall response (DOR) based on RECIST 1.1
Time Frame: 28 months
28 months

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
The correlation of potential predictive markers with the efficacy of the combination of pembrolizumab and exemestane/ leuprolide
Time Frame: 28 months

The predictive markers including:

  • PD-L1 expression in primary and metastatic tumors, as well as in circulating tumor cells
  • tumor infiltrating lymphocytes in primary and metastatic tumors
  • mutational load and neoantigens in metastatic tumors
  • change in cancer immune response profile between primary and metastatic tumors
  • luminal type change by PAM50 in primary and metastatic tumors
28 months

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.
National Taiwan University Hospital

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.
Merck Sharp & Dohme LLC

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.
September 15, 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.
August 16, 2022

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.
August 16, 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 1, 2016

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.
December 8, 2016

First Posted (Estimate)

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.
December 13, 2016

Study Record Updates

Last Update Posted (Estimate)

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.
February 22, 2023

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.
February 20, 2023

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.
February 1, 2023

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.
  • 201610003MIFA

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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