Working… Menu

Study of Pembrolizumab Plus Fulvestrant in Hormone Receptor Positive, HER-2 Negative Advanced/Metastatic Breast Cancer Patients

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. Identifier: NCT03393845
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : October 27, 2021
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Nancy Chan, MD, Big Ten Cancer Research Consortium

Brief Summary:
Pembrolizumab Plus Fulvestrant in Hormone Receptor Positive, HER-2 Negative Advanced/Metastatic Breast Cancer Patients

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Pembrolizumab Drug: Fulvestrant Phase 2

Detailed Description:

This is a non-randomized, multi-site, open-label Phase II trial for subjects with metastatic, hormone receptor positive, HER2 negative breast cancer. The study will enroll 47 patients to evaluate the anti-tumor activity of pembrolizumab with fulvestrant as measured by RECIST 1.1 tumor response and by progression free survival. We expect that if the immune response is augmented by the addition of pembrolizumab, significant change in durability of response will be noted.

Patients will be treated with pembrolizumab dosed at 200 mg intravenous infusion in combination with standard fulvestrant 500mg intramuscular injection.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Pembrolizumab Plus Fulvestrant in Hormone Receptor Positive, HER-2 Negative Advanced/Metastatic Breast Cancer Patients: Big Ten Cancer Research Consortium BTCRC-BRE16-042
Actual Study Start Date : January 29, 2018
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Pembrolizumab + Fulvestrant
Pembrolizumab 200m IV q3W + Fulvestrant. Loading dose 500mg IV IM q2W x3 followed by 500mg IM q4W
Drug: Pembrolizumab
Pembrolizumab 200mg IV, 21 day cycles
Other Name: Keytruda

Drug: Fulvestrant
Fulvestrant, 500mg IM, 28 day cycles.
Other Name: Faslodex

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 36 months ]
    To evaluate the overall response rate (ORR) defined as the percentage of patiences that achieve CR, PR, or SD for a minimum of four months, of pembrolizumab plus fulvestrant in patients with hormone receptor positive, HER2 negative advanced/metastatic breast cancer per RECIST version 1.1 criteria and irRECIST.

Secondary Outcome Measures :
  1. Safety profile of pembrolizumab plus fulvestrant [ Time Frame: 36 months ]
    To describe the toxicity profile of pembrolizumab plus fulvestrant in patients with hormone receptor positive, HER2 negative advanced/metastatic breast cancer. The toxicity profile will report all grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4

Other Outcome Measures:
  1. Progression free survival [ Time Frame: 36 months ]
    Progression free survival is defined as the time from date of treatment start until the criteria for disease progression is met or death from any cause. PFS will be assessed by RECIST 1.1 and irRECIST

  2. Durable response rate [ Time Frame: 36 months ]
    Durable response rate is defined as the number of months that a stable disease, partial or complete response is observed.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Men [29] and women ≥ 18 years of age at the time of informed consent.
  • ECOG Performance Status of 0 or 1 within 28 days prior to registration.
  • Histologic or cytologic diagnosis of metastatic breast cancer
  • Has received no more than two lines of prior hormonal therapy for advanced non-resectable/metastatic disease or no more than two lines of prior chemotherapy for advanced non-resectable/metastatic disease. Prior or current fulvestrant is allowed. Combination therapy is considered as one regimen.
  • Tumor is estrogen receptor positive (ER+) and/or (PR+), HER-2 negative (HER2-). ER and PR positivity is defined as >1%. HER-2 negative is defined as by IHC (0, 1+) or FISH. HER2 positive test result includes: Single-probe average HER2 copy number ≥6.0 signals/cell; Dual-probe HER2/CEP17 ratio ≥2.0 with an average HER2; copy number ≥4.0 signals/cell; Dual-probe HER2/CEP17 ratio ≥2.0 with an average HER2copy number <4.0 signals/cell; or Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number ≥6.0 signals/cell. Equivocal findings for IHC as 2+ should be reflexed to FISH. Equivocal results by FISH may be considered with approval from the Sponsor-Investigator.
  • Measurable disease based on RECIST 1.1 within 28 days prior to registration. Except in patients with bone-only disease, in the absence of measurable disease, evaluable bone lesion is allowed.

NOTE: Bone-only disease is allowed and biopsy is required. -Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.

NOTE: Subjects for whom newly-obtained fresh tissue samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor-Investigator.

  • Normal cardiac function as determined by treating physician per institutional standards via echocardiogram (ECHO) performed within 28 days prior to registration.
  • Prior chemotherapy must be completed at least 28 days prior to registration or at least 14 days prior to registration for targeted therapy.
  • Prior hormonal therapy or radiation therapy must be completed at least 14 days prior to registration. If subject is currently receiving fulvestrant, it may continue without interruption as per standard of care.
  • The subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline.

NOTE: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

NOTE: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to study registration, as determined by the enrolling physician.

  • Demonstrate adequate organ function as defined in the table below; all screening labs will be performed within 28 days of study registration.

    • Hematological ---Absolute Neutrophil Count (ANC): ≥ 1500/mm3 ---Platelets: ≥100,000 / mcL

      ---Hemoglobin (Hgb): ≥ 9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)

    • Renal

      ---Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≤1.5 × upper limit of normal (ULN) OR ≥30 mL/min for subjects with creatinine levels > 1.5 × institutional ULN

    • Hepatic

      ---Serum total bilirubin: ≤ 1.5 X ULN OR

      ---Direct bilirubin ≤ ULN for subjects with total bilirubin levels: > 1.5 ULN

      ---AST (SGOT) and ALT (SGPT): ≤ 2.5 × ULN

      ---Albumin: >2.5 mg/dL

    • Coagulation

      • International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT): ≤1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
      • aCreatinine clearance will be calculated per institutional standard.
  • Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to study registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

NOTE: Females are considered of childbearing potential unless: they are postmenopausal; are surgically sterile; or they have a congenital or acquired condition that prevents childbearing. See Section 5.6.2 for definitions.

NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

-Females and males of reproductive potential must be willing to abstain from heterosexual activity which could result in pregnancy or agree to use an adequate method of contraception as outlined in Section 5.6.2. Hormonal contraceptives are contraindicated in this population and are not allowed. Contraception will begin from the time of informed consent through 120 days after the last dose of study drug(s).

Exclusion Criteria:

  • Is currently receiving an investigational agent or has received an investigational agent or used an investigational device within 28 days of study registration.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study registration.

Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.

NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

  • Has a known history of active TB (Bacillus Tuberculosis). NOTE: TB testing is not required.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). NOTE: HIV testing is not required.
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

NOTE: Hepatitis B and Hepatitis C testing is not required.

  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has received prior chemotherapy within 28 days prior to study registration or has received prior hormonal/targeted therapy within 14 days prior to study registration
  • More than two lines of chemotherapy or more than two lines of hormonal therapy excludes participation.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Has known history of non-infectious pneumonitis/interstitial lung disease that required steroids or has any evidence of active pneumonitis/interstitial lung disease.
  • Has known history of, or any evidence of active interstitial lung disease, Class II-IV congestive heart failure, or myocardial infarction within 6 months from randomization.
  • Active infection requiring systemic therapy.
  • 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.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Breastfeeding during the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.

NOTE: breast milk cannot be stored for future use while the mother is being treated on study.

  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has received a live vaccine or live-attenuated vaccine within 30 days of study registration. Administration of killed vaccines is allowed.

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 identifier (NCT number): NCT03393845

Layout table for location contacts
Contact: Nancy Chan, MD 1 732-235-9692
Contact: Kristi Wilmes 317-634-5842 ext 62

Layout table for location information
United States, Michigan
Michigan State University, Breslin Cancer Center Recruiting
Lansing, Michigan, United States, 48910
Contact: Trinh Tran    517-975-9532   
Contact: Marybeth Blythe    517.975.9535   
Principal Investigator: Jatin Rana, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Eugene Sehi    402-559-8514   
Principal Investigator: Pavankumar Tandra, MD         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Nancy Chan, MD    732-235-9692   
Principal Investigator: Nancy Chan, MD         
Sub-Investigator: Deborah Toppmeyer, MD         
Sponsors and Collaborators
Nancy Chan, MD
Merck Sharp & Dohme Corp.
Layout table for investigator information
Principal Investigator: Nancy Chan Rutgers Cancer Institute of New Jersey
Layout table for additonal information
Responsible Party: Nancy Chan, MD, Sponsor Investigator, Big Ten Cancer Research Consortium Identifier: NCT03393845    
Other Study ID Numbers: BTCRC-BRE16-042
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: October 27, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs