Clinical Trials /

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

NCT02990845

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Exemestane/ Leuprolide in Premenopausal HR+/ HER2- Locally Advanced or Metastatic Breast Cancer
  • Official Title: A Pilot Study of Pembrolizumab and Exemestane/ Leuprolide in Premenopausal Hormone Receptor Positive/ HER2 Negative Locally Advanced or Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 201610003MIFA
  • NCT ID: NCT02990845

Conditions

  • Premenopausal Breast Cancer

Interventions

DrugSynonymsArms
Pembrolizumab/ Exemestane/ LeuprolidePembrolizumab/ Exemestane/ Leuprolide

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab/ Exemestane/ LeuprolideExperimentalDose 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
  • Pembrolizumab/ Exemestane/ Leuprolide

Eligibility 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 estradiol10pg/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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:The PFS rate at 8 months
Time Frame:28 months
Safety Issue:
Description: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

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Taiwan University Hospital

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