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A Randomized Phase II Study Of Eribulin Mesylate With or Without Pembrolizumab For Metastatic Hormone Receptor Positive Breast Cancer

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03051659
Recruitment Status : Active, not recruiting
First Posted : February 14, 2017
Last Update Posted : April 28, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sara Tolaney, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE February 8, 2017
First Posted Date  ICMJE February 14, 2017
Last Update Posted Date April 28, 2020
Actual Study Start Date  ICMJE March 22, 2017
Estimated Primary Completion Date August 25, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
Progression Free Survival [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
  • Objective Response Rate [ Time Frame: 2 years ]
  • Overall Survival Rate [ Time Frame: 2 years ]
  • Immune Response Rate [ Time Frame: 2 years ]
  • Duration of Response [ Time Frame: 2 years ]
  • Clinical Benefit Rate [ Time Frame: 27 weeks ]
  • Incidence Rate of each Toxicity (safety and tolerability). [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Randomized Phase II Study Of Eribulin Mesylate With or Without Pembrolizumab For Metastatic Hormone Receptor Positive Breast Cancer
Official Title  ICMJE A Randomized Phase II Study Of Eribulin Mesylate With Or Without Pembrolizumab For Metastatic Hormone Receptor Positive Breast Cancer
Brief Summary This research study is exploring chemotherapy in combination with immunotherapy (a therapy that uses the body's own immune system to control cancer) as a possible treatment for metastatic hormone receptor positive breast cancer.
Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

In this research study, The investigators are evaluating the safety and effectiveness of Eribulin mesylate with or without Pembrolizumab in metastatic hormone receptor positive breast cancer.

The FDA (the U.S. Food and Drug Administration) has not approved the combination of Pembrolizumab and Eribulin mesylate for Breast Cancer.

The FDA has not approved Pembrolizumab for this specific type of breast cancer but it has been approved in the United States for other diseases.

The FDA has approved Eribulin mesylate as a treatment option for this type of breast cancer.

Pembrolizumab is a medicine that may treat cancer by working with the immune system. The immune system is the body's natural defense against disease. The immune system sends types of cells called "T cells" throughout the body to detect and fight infections and diseases, including cancer. For some types of cancer, the T cells do not work as they should and are prevented from attacking the tumors. Pembrolizumab is thought to work by blocking a protein in the T cells called PD-1 ("programmed death 1"), which then may allow these cells and other parts of the immune system to attack tumors.

Eribulin mesylate is developed from a natural substance found in a sea sponge. Eribulin mesylate works by preventing cancer cells from multiplying.

The combination of Pembrolizumab and Eribulin mesylate is investigational. The study drugs, when given separately, work in different ways to stop the cancer cells from growing and spreading. However, it is not known if giving the two study drugs at the same time will have a better anti-cancer effect than giving each treatment on its own.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Eribulin Mesylate
    Eribulin mesylate is developed from a natural substance found in a sea sponge. Eribulin mesylate works by preventing cancer cells from multiplying
    Other Name: Halaven
  • Drug: Pembrolizumab
    Pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells.
    Other Name: Keytruda
Study Arms  ICMJE
  • Experimental: Eribulin Mesylate
    • Eribulin mesylate will be administered on Days 1 and 8 of each 21 day cycle.
    • Eribulin mesylate will be administered intravenously
    Intervention: Drug: Eribulin Mesylate
  • Experimental: Eribulin Mesylate Combine with Pembrolizumab
    • Pembrolizumab will be administered in clinic once per cycle
    • Pembrolizumab will be given intravenously prior to Eribulin Mesylate
    • Eribulin mesylate will be administered on Days 1 and 8 of each 21 day cycle.
    • Eribulin mesylate will be administered intravenously
    Interventions:
    • Drug: Eribulin Mesylate
    • Drug: Pembrolizumab
Publications * Tolaney SM, Barroso-Sousa R, Keenan T, Li T, Trippa L, Vaz-Luis I, Wulf G, Spring L, Sinclair NF, Andrews C, Pittenger J, Richardson ET 3rd, Dillon D, Lin NU, Overmoyer B, Partridge AH, Van Allen E, Mittendorf EA, Winer EP, Krop IE. Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1598-1605. doi: 10.1001/jamaoncol.2020.3524.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 9, 2017)
88
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 25, 2024
Estimated Primary Completion Date August 25, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Patients must have histologically or cytologically confirmed Stage IV invasive breast cancer. Patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
  • Subjects must have at least one lesion that is not within a previously radiated field that is evaluable on computerized tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST version 1.1.46 If the subject's only evaluable disease is within a previously radiated field, it must have demonstrated progression since the time of radiation.
  • Participants must have HR positive, HER2-negative breast cancer (ER>1% and/or, PR>1%, HER2-negative per ASCO CAP guidelines, 2013 resulted on the primary tumor and/or a metastatic lesion).
  • Participants must have already received or been intolerant to at least two lines of hormonal therapies (including the adjuvant or metastatic setting) or be appropriate candidates for chemotherapy
  • Prior chemotherapy: Participants are allowed to have received up to 2 prior lines of chemotherapy in the metastatic setting. If a prior chemotherapy was given for less than 1 cycle, it will not be counted as a prior line. The last dose of chemotherapy must be ≥14 days prior to initiation of study therapy. Participants should be adequately recovered from acute toxicities of prior treatment. No prior treatment with eribulin mesylate is allowed.
  • Prior biologic therapy: The last dose of biologic or investigational therapy must be ≥21 days prior to initiation of study therapy.
  • Prior hormonal therapy: Hormonal therapy must have been discontinued ≥14 days prior to initiation of study therapy. However, continuation of ovarian suppression is allowed.
  • Prior radiation therapy: Participants may have received prior radiation therapy in either the metastatic or early-stage setting. Radiation therapy must be completed ≥14 days prior to initiation of study therapy.
  • Prior targeted therapy: Targeted therapy must have been discontinued ≥ 14 days prior to initiation of study therapy.
  • Biphosphonates/Denosumab: Participants on bisphosphonates/denosumab may continue receiving bisphosphonate therapy during study treatment.
  • Participants must have an archival tumor sample available (1 block or 20 unstained slides). If no archival tissue is available, participants must be willing to undergo a research biopsy of their disease if it is safely accessible.
  • Age ≥ 18 years of age
  • ECOG performance status ≤2 (Karnofsky ≥60%)
  • Participants must have normal organ and marrow function as defined below:
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • hemoglobin ≥ 8 g/dl
  • total bilirubin ≤1.5 × institutional upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN (≤ 5 × institutional ULN with documented liver metastases,
  • serum creatinine ≤1.5mg/dL or calculated GFR ≥60 mL/min
  • INR/PT ≤1.5 times ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • aPTT/PTT ≤1.5 times ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • The effects of eribulin mesylate and pembrolizumab on the developing human fetus are unknown. Pre-clinical data was suggestive of a teratogenic effect of eribulin mesylate. For these reasons women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and 4 months after the last dose of eribulin mesylate and/or pembrolizumab. Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

    • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the treating physician and principal investigator should be informed immediately.
    • While on the study, women must not breastfeed.
    • Subjects of childbearing potential are defined as those who have not been surgically sterilized and/or have had a menstrual period in the past year
  • Female subjects of childbearing potential, as defined above, must have a either a negative urine or a negative serum pregnancy test within seven (7) days of first dose of pembrolizumab. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

  • Chemotherapy-related or radiation-related toxicities that have not resolved to Grade 1 severity or lower, except for stable sensory neuropathy (≤ Grade 2) and alopecia.
  • Participants who are receiving any other investigational agents.
  • Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2 agent or participation in any MK-3475 Merck studies.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to eribulin mesylate or pembrolizumab.
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with previously diagnosed brain metastases are eligible if they have completed treatment at least 4 weeks prior to registration, are neurologically stable and absence of new neurologic symptoms for the last 4 weeks prior to study entry, and have recovered from the effects of radiotherapy or surgery. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥2 weeks before the first study drug. Treatment for brain metastases may have included whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician.
  • Uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, chronic liver or renal disease, severe malnutrition or psychiatric illness/social situations that would limit compliance with study requirements.
  • 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 >500 ms).
  • Medcial condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, participants with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • History or evidence of active, noninfectious pneumonitis that required treatment with steroids.
  • History of interstitial lung disease.
  • Participants known to be positive for the human immunodeficiency virus (HIV), Hepatitis B antigen (HepBsAg), or Hepatitis C virus (HCV) RNA. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Pembrolizumab and/or eribulin mesylate. In addition, these participants are at increased risk of lethal infections.
  • Individuals with a history of a second malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and non-melanoma cancer of the skin. Patients with other cancers diagnosed within the past 5 years and felt to be at low risk of recurrence should be discussed with the study sponsor to determine eligibility.
  • Has received a live vaccine within 28 days of planned start of study therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03051659
Other Study ID Numbers  ICMJE 16-577
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sara Tolaney, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Sara Tolaney, MD MPH Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP