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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02990845
Recruitment Status : Recruiting
First Posted : December 13, 2016
Last Update Posted : April 13, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Premenopausal Breast Cancer Drug: Pembrolizumab/ Exemestane/ Leuprolide Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Pembrolizumab and Exemestane/ Leuprolide in Premenopausal Hormone Receptor Positive/ HER2 Negative Locally Advanced or Metastatic Breast Cancer
Actual Study Start Date : September 15, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 28 months ]
  2. The PFS based on RECIST 1.1 [ Time Frame: 28 months ]
  3. The overall response rate (ORR) based on RECIST 1.1 [ Time Frame: 28 months ]
  4. The clinical benefit rate (CBR) based on RECIST 1.1 [ Time Frame: 28 months ]
  5. The duration of overall response (DOR) based on RECIST 1.1 [ Time Frame: 28 months ]

Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02990845


Contacts
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Contact: Yen-Shen Lu, MD, PhD +886-2-23123456 yslu@ntu.edu.tw

Locations
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Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Yen-Shen Lu, MD, PhD    +886-2-23123456    yslu@ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Merck Sharp & Dohme Corp.
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Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02990845    
Other Study ID Numbers: 201610003MIFA
First Posted: December 13, 2016    Key Record Dates
Last Update Posted: April 13, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pembrolizumab
Leuprolide
Exemestane
Antineoplastic Agents, Immunological
Antineoplastic Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists