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Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Combination With Pembrolizumab in Subjects With Metastatic Triple-Negative Breast Cancer (mTNBC)

This study is currently recruiting participants.
Verified November 2017 by Eisai Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02513472
First Posted: July 31, 2015
Last Update Posted: November 7, 2017
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.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Eisai Inc.
  Purpose
This is an open-label, single-arm, multicenter, Phase 1b/2 study of eribulin mesylate in combination with pembrolizumab in participants with metastatic triple-negative breast cancer (mTNBC) previously treated with 0 to 2 lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting.

Condition Intervention Phase
Breast Cancer Drug: Eribulin Mesylate Drug: Pembrolizumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Arm Multicenter Phase 1b/2 Study to Evaluate the Efficacy and Safety of Eribulin Mesylate in Combination With Pembrolizumab in Subjects With Metastatic Triple-Negative Breast Cancer (mTNBC)

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) [ Time Frame: Up to 1 cycle (21 days) in Phase 1b part ]
  • Objective Response Rate (ORR) [ Time Frame: From date of first dose of study drug administration up to 38 months ]

Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurs first, or up to approximately 38 months ]
  • Overall Survival (OS) [ Time Frame: From date of first dose of study drug administration until date of death from any cause or up to approximately 38 months ]
  • Duration of Response (DOR) [ Time Frame: From the date that a confirmed OR is first documented to the date of progressive disease (PD) or death due to any cause for those subjects with a confirmed PR (partial response) or CR (complete response) or up to approximately 38 months ]
  • Clinical Benefit Rate (CBR) [ Time Frame: From the date that is confirmed BOR (best overall response) of CR complete response),PR (partial response) or durable stable disease(SD) (≥ 24Weeks) ]
  • ORR in the PD-L1 positive subset [ Time Frame: From date of first dose of study drug administration up to 38 months ]
  • PFS in the PD-L1 positive subset [ Time Frame: From date of first dose of study drug administration to date of first documentation of disease progression or death, whichever occurs first, or up to approximately 38 months ]
  • OS in the PD-L1 positive subset [ Time Frame: From date of first dose of study drug administration until date of death from any cause or up to approximately 38 months ]
  • DOR in the PD-L1 positive subset [ Time Frame: From the date that a confirmed OR is first documented to the date of PD or death due to any cause for those subjects with a confirmed PR or CR or up to approximately 38 months ]
  • CBR in the PD-L1 positive subset [ Time Frame: From date of the first dose of the study drug administration up to 38 months ]

Estimated Enrollment: 150
Actual Study Start Date: August 28, 2015
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eribulin Mesylate + Pembrolizumab
Participants with metastatic triple-negative breast cancer (mTNBC) previously treated with 0 to 2 lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting
Drug: Eribulin Mesylate
Eribulin Mesylate will be administered as a 1.4 mg/m2 IV (intravenous) infusion on Day 1 and Day 8 of each 21-day cycle in the presence of clinical benefit until intercurrent illness, unacceptable toxicity, or disease progression occurs, or until the subject withdraws consent.
Other Name: Halaven, E7389
Drug: Pembrolizumab
Pembrolizumab will be administered as a 200 mg IV infusion on Day 1 of each 21-day cycle in the presence of clinical benefit until intercurrent illness, unacceptable toxicity, or disease progression occurs, or until the subject withdraws consent.
Other Name: Keytruda, MK-3475

Detailed Description:
The Phase 1b part will evaluate the safety and tolerability of eribulin mesylate in combination with pembrolizumab. Approximately 6 participants may be enrolled in the Phase 1b part of the study. The Phase 2 part will evaluate the tumor objective responses when treated with eribulin mesylate in combination with pembrolizumab in participants with mTNBC previously treated with 0 to 2 lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting. Approximately 106 mTNBC participants (including participants in Phase 1b who are on RP2D level) will be enrolled in Phase 2.
  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Females or males, aged greater than or equal to 18 years at the time of signing the informed consent form (ICF)
  2. Metastatic triple-negative breast cancer (confirmed from most recent tissue sample) meeting the following criteria:

    1. Estrogen receptor (ER) and progesterone receptor negative (a tumor is ER and/or progesterone receptor positive if at least 1% of the cells examined have estrogen and/or progesterone receptors) and human epidermal growth factor receptor 2 (HER2) negative (defined as immunohistochemistry [IHC] <2+ or fluorescence in situ hybridization [FISH] negative).
    2. Previously treated with 0 to 2 lines of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting. Hormonal therapy and bone metastases treatment (eg, bisphosphonates, denosumab, etc) are not considered forms of systemic anticancer therapy.
  3. Presence of measurable disease meeting the following criteria:

    1. At least 1 lesion of greater than or equal to 10 mm in long axis diameter for nonlymph nodes or greater than or equal to 15 mm in short axis diameter for lymph nodes that is serially measurable according to RECIST 1.1 using computerized tomography or magnetic resonance imaging or panoramic and close-up color photography
    2. Lesions that have had radiotherapy must show subsequent radiographic evidence of increased size to be deemed a target lesion
  4. Life expectancy of greater than or equal to 3 months
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  6. Adequate renal function as evidenced by serum creatinine less than or equal to 1.5 mg/dL or calculated creatinine clearance greater than or equal to 50 mL/minute according to the Cockcroft and Gault formula
  7. Adequate bone marrow function, defined as:

    1. Absolute neutrophil count (ANC) greater than or equal to 1.5 X 10^9/L
    2. Hemoglobin (Hb) greater than or equal to 10.0 g/dL (can be corrected by growth factor or transfusion)
    3. Platelet count greater than or equal to 100 X 10^9/L
  8. Adequate liver function, defined as:

    1. Total bilirubin less than or equal to 1.5 X upper limit of normal (ULN)
    2. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN unless there are bone metastases, in which case liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase. ALT and AST ≤ 5 × ULN if subject has liver metastases
  9. Resolution of all chemotherapy-related or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (less than or equal to Grade 2) and alopecia
  10. Archived tissue sample or new biopsy sample
  11. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
  12. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month before dosing)
  13. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, a combination oral contraceptive (estrogen/progesterone), or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 120 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double barrier method as described above if she becomes sexually active during the study period or for 120 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 28 days before dosing and must continue to use the same contraceptive during the study and for 120 days after study drug discontinuation.
  14. Males who have had a successful vasectomy (confirmed azoospermia) or they and their female partners meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period or for 120 days after study drug discontinuation). No sperm donation is allowed during the study period or for 120 days after study drug discontinuation.
  15. Willing and able to comply with all aspects of the treatment protocol
  16. Provide written informed consent

Exclusion Criteria:

  1. Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2
  2. Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppresive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
  3. Less than 6 months since prior adjuvant chemotherapy
  4. Current enrollment in another interventional clinical study or used any investigational drug or device within the past 28 days preceding informed consent
  5. Treatment with chemotherapy or biological therapy within the previous 3 weeks, radiation or small molecule targeted therapy within the previous 2 weeks
  6. Known central nervous system (CNS) disease, except for those subjects with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period
  7. Known history of human immunodeficiency virus (HIV) positive
  8. Known active hepatitis B (eg, HBsAg reactive) or hepatitis C (eg, HCV RNA detected)
  9. Existing anticancer treatment-related toxicities of Grades greater than or equal to 2 (except for alopecia and Grade 2 sensory neuropathy) according to Common Terminology Criteria for Adverse Events (CTCAE v4.03)
  10. Any other malignancy that required treatment or has shown evidence of recurrence (except for nonmelanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 5 years prior to enrollment in this study
  11. History of significant cardiovascular disease, defined as:

    1. congestive heart failure greater than New York Heart Association (NYHA) Class II according to the NYHA Functional Classification
    2. unstable angina or myocardial infarction within 6 months of enrollment
    3. serious cardiac arrhythmia
  12. Clinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT/QTc ([QT interval/corrected QT interval], eg, a repeated demonstration of a QTc interval greater than 500 ms)
  13. History of concomitant medical conditions or infectious diseases that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study
  14. Hypersensitivity to the active substance or any other excipients of the eribulin mesylate drug product, or or severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
  15. Scheduled for major surgery during the study
  16. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor
  17. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  18. Has a history of interstitial lung disease
  19. Has an active infection requiring systemic therapy
  20. Has received a live-virus vaccination within 30 days of planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted.
  21. The investigator's belief that the subject is medically unfit to receive eribulin mesylate and pembrolizumab or unsuitable for any other reason
  Contacts and Locations
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): NCT02513472


Contacts
Contact: Med Info 888-274-2378

Locations
United States, California
City of Hope National Medical Center Active, not recruiting
Duarte, California, United States, 91010
Sansum Clinic Completed
Santa Barbara, California, United States, 93105
United States, Colorado
Rocky Mountain Cancer Centers Active, not recruiting
Denver, Colorado, United States, 80218
United States, Florida
Baptist Medical Group Active, not recruiting
Miami, Florida, United States, 33176
SCRI Florida Cancer Specialists East Completed
West Palm Beach, Florida, United States, 33401
United States, Massachusetts
Beth Israel Deaconess Medical Center Active, not recruiting
Boston, Massachusetts, United States, 02115
Dana Farber Cancer Institute Active, not recruiting
Boston, Massachusetts, United States, 02115
United States, Minnesota
Minnesota Oncology Hematology PA Active, not recruiting
Minneapolis, Minnesota, United States, 55407
United States, Missouri
Washington University Active, not recruiting
Saint Louis, Missouri, United States, 63110
United States, New Hampshire
Dartmouth Hitchcock Medical Center Active, not recruiting
Lebanon, New Hampshire, United States, 03756
United States, New York
Columbia University Medical Center Active, not recruiting
New York, New York, United States, 10032
Weill Cornell Medical College Active, not recruiting
New York, New York, United States, 10065
United States, Tennessee
Chattanooga Oncology Hematology Associates Recruiting
Chattanooga, Tennessee, United States, 37404
SCRI Tennessee Oncology Nashville Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology Active, not recruiting
Austin, Texas, United States, 78731
Center For Cancer and Blood Disorders Completed
Fort Worth, Texas, United States, 76104
Cancer Care Network of South Texas Active, not recruiting
San Antonio, Texas, United States, 78217
University of Texas Health Science Center San Antonio Active, not recruiting
San Antonio, Texas, United States, 78229
Texas Cancer Center Sherman Completed
Sherman, Texas, United States, 75090
United States, Virginia
Oncology and Hematology Associates of Southwest Virginia Inc Active, not recruiting
Salem, Virginia, United States, 24153
Shenandoah Oncology Association Active, not recruiting
Winchester, Virginia, United States, 22601
United States, Wisconsin
University of Wisconsin Carbone Cancer Center Active, not recruiting
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Eisai Inc.
Merck Sharp & Dohme Corp.
Investigators
Study Director: Dr. Claudio Savulsky Eisai Inc.
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT02513472     History of Changes
Other Study ID Numbers: E7389-M001-218
KEYNOTE-150 ( Other Identifier: Merck Sharp and Dohme Corp )
First Submitted: July 29, 2015
First Posted: July 31, 2015
Last Update Posted: November 7, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Eisai Inc.:
Eribulin Mesylate
Pembrolizumab
Metastatic Triple-Negative Breast Cancer
mTNBC

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pembrolizumab
Antineoplastic Agents