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Breast CancerPhase 2NCT03051659

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

A Phase 2 study testing Eribulin Mesylate and Pembrolizumab in people with Breast Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Eribulin Mesylate and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
3 sitesUnited States
Study dates
22 Mar 2017to 5 Sep 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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. 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Randomized Phase II Study Of Eribulin Mesylate With Or Without Pembrolizumab For Metastatic Hormone Receptor Positive Breast Cancer

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.

Read the 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.

Conditions
Breast Cancer
Being tested
Eribulin Mesylate, Pembrolizumab
Keywords
Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Eribulin MesylateDrug

    Also called Halaven

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

  • PembrolizumabDrug

    Also called Keytruda

    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.

Study groups in NCT03051659
Study groupRoleWhat they receive
Eribulin MesylateExperimental-Eribulin mesylate will be administered on Days 1 and 8 of each 21 day cycle for 1.4mg/m^2 intravenously.
Receives: Drug: Eribulin Mesylate
Eribulin Mesylate Combine with PembrolizumabExperimental* Pembrolizumab will be administered in clinic once per cycle, given 200mg/m^2 intravenously prior to Eribulin Mesylate. * Eribulin mesylate will be administered on Days 1 and 8 of each 21 day cycle for 1.4 mg/m^2 intravenously.
Receives: Drug: Eribulin Mesylate; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median Progression Free Survival (PFS)

    Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

    Measured: Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. Median follow-up 10.5 months with range 0.43-19 months.

Secondary outcomes (5)

  1. Objective Response Rate (ORR)

    The objective response rate (ORR) was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

    Measured: Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. If after Cycle 18 scans, a participant has SD or better by RECIST the frequency of assessments may be reduced to every 4 cycles, up to a maximum of 18 months.

  2. Median Overall Survival (OS)

    OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive. Patients who discontinued treatment to pursue potentially curative resection were censored for progression-free survival at the time of surgery. Patients who had not experienced cancer progression or died were censored at their last known follow-up date.

    Measured: Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. Median follow-up 10.5 months with range 0.43-19 months.

  3. Median Duration of Response (DOR)

    DOR is defined as the time from CR or PR achieved until renewed disease progression is detected. DOR will be calculated per RECIST 1.1 and irRECIST criteria.

    Measured: Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. If after Cycle 18 scans, a participant has SD or better by RECIST the frequency of assessments may be reduced to every 4 cycles.

  4. Clinical Benefit Rate (CBR)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. If after Cycle 18 scans, a participant has SD or better by RECIST the frequency of assessments may be reduced to every 4 cycles, up to a maximum of 18 months.

  5. Number of Participants With Grade 3 or Higher Treatment-Related Toxicity

    All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.

    Measured: Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. If after Cycle 18 scans, a participant has SD or better by RECIST the frequency of assessments may be reduced to every 4 cycles, up to a maximum of 18 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Feb 2017
  2. Study start22 Mar 2017
  3. Primary completion11 Oct 2018
  4. Study completion5 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03051659
Sponsor's protocol ID
16-577
Status last verified
Mar 2024
First submitted
8 Feb 2017
Last updated
6 Mar 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Keenan TE, Guerriero JL, Barroso-Sousa R, Li T, O'Meara T, Giobbie-Hurder A, Tayob N, Hu J, Severgnini M, Agudo J, Vaz-Luis I, Anderson L, Attaya V, Park J, Conway J, He MX, Reardon B, Shannon E, Wulf G, Spring LM, Jeselsohn R, Krop I, Lin NU, Partridge A, Winer EP, Mittendorf EA, Liu D, Van Allen EM, Tolaney SM. Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer. Nat Commun. 2021 Sep 21;12(1):5563. doi: 10.1038/s41467-021-25769-z.

    PubMed 34548479

  • 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.

    PubMed 32880602

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Eribulin Mesylate and Pembrolizumab in people with Breast Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Progression Free Survival (PFS) (time frame: Disease assessments is performed every 3 cycles (3 weeks/cycle) for the first 18 cycles. Median follow-up 10.5 months with range 0.43-19 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03051659, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2024.

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