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CompletedNCT01401959Updated Jun 15, 2018Results posted

Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy

A Phase 2 interventional study of Eribulin and Trastuzumab in Metastatic Breast Cancer, sponsored by SCRI Development Innovations, LLC. Completed at 18 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-06-15.

Sponsored by SCRI Development Innovations, LLC · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
127
Allocation
Non-randomized
Ages
18 Years and older
Sex
Female
01

Study summary

The investigators propose to evaluate eribulin as adjuvant therapy in breast cancer patients who have residual invasive disease in breast or lymph node tissue following standard neoadjuvant chemotherapy and surgery regimen. Three cohorts of patients will be evaluated separately based on tumor type: triple-negative, hormone-receptor-positive/HER2-negative, and HER2-positive breast cancers.

Read the detailed description

This is a non-randomized, open-label trial to evaluate 6 cycles of eribulin in female patients with invasive breast cancer who do not achieve pathologic complete response (pCR) after treatment with a standard neoadjuvant chemotherapy and surgery regimen. Patients will be randomized into three cohorts according to tumor-type: triple-negative (Cohort A), hormone-receptor-positive/HER2-negative (Cohort B), and HER2-positive (Cohort C) tumors. Patients will receive eribulin for 6 cycles (1 cycle = 21 days). Patients with HER2-positive tumors will also receive trastuzumab. Patients in all cohorts will be allowed to receive locoregional radiotherapy and/or adjuvant hormonal therapy per institutional guidelines.

02

Conditions studied

  • Metastatic Breast Cancer

Keywords

  • Metastatic Breast Cancer
  • Adjuvant
  • Residual Disease
  • eribulin
  • Trastuzumab
03

In context

Pathologic Complete Response

81 studies on the registry are indexed under Pathologic Complete Response; 42 are open to participants now.

This study's enrollment of 127 is above the median of 75 across 62 interventional studies indexed under Pathologic Complete Response.

Browse Pathologic Complete Response studies →

Lead sponsor

SCRI Development Innovations, LLC is the lead sponsor of 174 studies on the registry; 5 are open to participants now.

Of its 15 completed or terminated interventional studies of FDA-regulated products, 15 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  1. Female patients >=18 years-of-age.
  2. Histologically confirmed breast cancer prior to surgery with the following staging criteria: T1-T3, T4a, T4b, N0-N2, N3a and M0 (T1N0M0 patients are excluded). Inflammatory disease is excluded.
  3. Previous treatment with a minimum of 4 cycles of neoadjuvant anthracycline and/or taxane containing chemotherapy (+trastuzumab in HER2-positive patients).
  4. Patients must be ≥ 21 days and ≤ 84 days from breast surgery and fully recovered. Patients may have had mastectomy or breast conservation surgery with axillary node dissection.
  5. Pathologic CR (pCR) not achieved following neoadjuvant treatment (i.e., residual invasive breast cancer (>5 mm) in the breast or presence of nodal disease at surgery [ypT0/T1a, N1-N3a, M0 or ypT1b-T4, N0-N3a, M0].
  6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
  7. Recovery from any toxic effects of prior therapy to \<=Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0) except fatigue or alopecia.
  8. Peripheral neuropathy Grade \<=2 per NCI CTCAE v4.0 at trial entry.
  9. Normal left ventricular ejection fraction (LVEF), within the institutional limits of normal, as measured by echocardiography (ECHO) or multi-gated (MUGA) scan in patients to receive trastuzumab with eribulin (HER2-positive).
  10. Adequate hematologic, hepatic, and renal function
  11. Complete staging work-up to confirm localized disease should include computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), a CT scan of the head or MRI of the brain (if symptomatic), and either a positron emission tomography (PET) scan or a bone scan. (Note: a PET/CT is acceptable for baseline imaging in lieu of CT examinations or bone scan). Negative scans performed prior to the initiation of neoadjuvant therapy, or at any subsequent time, are acceptable and do not need to be repeated.
  12. Female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum pregnancy test performed within 7 days prior to start of trial treatment.
  13. Willingness and ability to comply with trial and follow-up procedures.
  14. Ability to understand the investigative nature of this trial and give written informed consent.
  15. Agree to delay in reconstruction in terms of implants placed in setting of expanders until chemotherapy is completed and the patient has recovered. Expansion of expanders may continue during trial treatment.

Exclusion criteria

Exclusion Criteria:

  1. Presence of other active cancers, or history of treatment for invasive cancer \<3 years prior to trial entry (except thyroid, cervical cancer). Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
  2. Radiotherapy prior to the start of study treatment.
  3. History or clinical evidence of central nervous system metastases or other metastatic disease.
  4. Non-healed surgical wound.
  5. Known or suspected allergy/hypersensitivity to eribulin.
  6. Cardiac disease, including: congestive heart failure Class II-IV per New York Heart Association classification;cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months.
  7. Chronic use of drugs that cause QTc prolongation.Patients must discontinue use of these drugs 7 days prior to the start of study treatment.
  8. Women who are pregnant or lactating. All females of child-bearing potential must have negative serum pregnancy test within 48 hours prior to trial treatment.
  9. Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
  10. Prolongation of heart rate-corrected QT interval (QTc) >480 msecs (using Bazett's formula).
  11. Minor surgical procedures (with the exception of the placement of port-a-cath or other central venous access) performed less than 7 days prior to beginning protocol treatment.
  12. History of cerebrovascular accident including transient ischemic attack (TIA), or untreated deep venous thrombosis (DVT)/ pulmonary embolism (PE) within the past 6 months. Note: Patients with recent DVT/PE receiving treatment with a stable dose of therapeutic anti-coagulating agents are eligible.
  13. Patients may not receive any other investigational or anti-cancer treatments while participating in this trial.
  14. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the trial participation or investigational product(s) administration or may interfere with the interpretation of the results.
  15. Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
127 participants (actual)

Study arms

  • Experimental
    Cohort A: Triple-negative breast cancer

    Eribulin 1.4 mg/m\^2 intravenously (IV)

    Drug: Eribulin

  • Experimental
    Cohort B: ER/PR+ /HER2- breast cancer

    Eribulin 1.4 mg/m\^2 intravenously (IV)

    Drug: Eribulin

  • Experimental
    Cohort C: HER2+ breast cancer

    Eribulin 1.4 mg/m\^2 intravenously (IV) Trastuzumab 6mg/kg intravenously (IV)

    Drug: Eribulin · Drug: Trastuzumab

Interventions

  • DrugEribulin

    1.4 mg/m\^2 IV Days 1 and 8, every 21 days for six cycles

    Also known as: Halaven

  • DrugTrastuzumab

    6 mg/kg IV Day 1 every 21 days

    Also known as: Herceptin

06

What researchers measure

Primary outcomes

  1. Percentage of Patients With a 2 Year Disease-Free Survival (DFS) as a Measure of Efficacy

    The percentage of patients that are without evidence of disease recurrence at the 2 year timepoint, as measured from date of first protocol treatment date to first documented disease progression date or date of death from any cause, whichever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Time frame: Up to 2 years

Secondary outcomes

  1. Number of Patients Who Completed Eribulin Therapy as an Assessment of Treatment Feasibility

    Examines the feasibility of administering 6 cycles (21 days per cycle) of eribulin without toxicity or disease worsening following standard neoadjuvant chemotherapy and surgery.

    Time frame: up to 18 weeks

  2. The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety

    A treatment-related adverse event or serious adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events and serious adverse events will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.03.

    Time frame: Weekly during each 21 day cycle and for 30 days after completion of protocol-specific treatment. After that patients were followed every 3 months for up to 2 years.

07

Results

Posted May 7, 2018

Participant flow

Between September 2011 to April 2015, 127 female patients who did not achieve a pathologic complete response (pCR i.e. have residual invasive disease in breast or lymph node tissue) after treatment with a standard neoadjuvant chemotherapy regimen and surgery were enrolled. Of those 127 patients enrolled, 126 patients received treatment.

Enrolled
Participant flow — Enrolled
MilestoneCohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast CancerCohort C: HER2-positive Breast Cancer Patients
Started544231
Completed534231
Not completed100
Withdrew: Withdrawal by subject100
Treated
Participant flow — Treated
MilestoneCohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast CancerCohort C: HER2-positive Breast Cancer Patients
Started534231
Completed463426
Not completed785
Withdrew: Disease progression221
Withdrew: Adverse event432
Withdrew: Withdrawal by subject122
Withdrew: Protocol violation010

Outcome measures

PrimaryPercentage of Patients With a 2 Year Disease-Free Survival (DFS) as a Measure of Efficacy

The percentage of patients that are without evidence of disease recurrence at the 2 year timepoint, as measured from date of first protocol treatment date to first documented disease progression date or date of death from any cause, whichever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame:
Up to 2 years
Reported as:
Number · percentage of patients
Percentage of Patients With a 2 Year Disease-Free Survival (DFS) as a Measure of Efficacy
percentage of patientsCohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast Cancer PatientsCohort C: HER2-positive Breast Cancer Patients
Percentage of Patients With a 2 Year Disease-Free Survival (DFS) as a Measure of Efficacy56 (42 to 69)83 (67 to 91)73 (53 to 86)
SecondaryNumber of Patients Who Completed Eribulin Therapy as an Assessment of Treatment Feasibility

Examines the feasibility of administering 6 cycles (21 days per cycle) of eribulin without toxicity or disease worsening following standard neoadjuvant chemotherapy and surgery.

Time frame:
up to 18 weeks
Reported as:
Count of participants · Participants
Number of Patients Who Completed Eribulin Therapy as an Assessment of Treatment Feasibility
ParticipantsCohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast CancerCohort C: HER2-positive Breast Cancer Patients
Number of Patients Who Completed Eribulin Therapy as an Assessment of Treatment Feasibility463426
SecondaryThe Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety

A treatment-related adverse event or serious adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events and serious adverse events will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.03.

Time frame:
Weekly during each 21 day cycle and for 30 days after completion of protocol-specific treatment. After that patients were followed every 3 months for up to 2 years.
Reported as:
Count of participants · Participants
The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety
ParticipantsCohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast CancerCohort C: HER2-positive Breast Cancer Patients
The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety504131

Adverse events

Collected over Day 1 and Day 8 of every treatment cycle and 30 days after discontinuation or completion of treatment for up to 22.2 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort A: Triple-negative Breast Cancer6/53 (11.3%)8/53 (15.1%)52/52 (100%)
Cohort B: ER/PR Positive/HER2-negative Breast Cancer4/42 (9.5%)1/42 (2.4%)42/42 (100%)
Cohort C: HER2 Positive Breast Cancer1/31 (3.2%)3/31 (9.7%)31/31 (100%)
Most frequent serious events
Showing 10 of 12
Most frequent serious events
EventCohort A: Triple-negative Breast CancerCohort B: ER/PR Positive/HER2-negative Breast CancerCohort C: HER2 Positive Breast Cancer
CellulitisInfections and infestations0/530/421/31
Diabetes mellitus inadequate controlMetabolism and nutrition disorders0/530/421/31
SinusitisInfections and infestations0/530/421/31
TracheobronchitisInfections and infestations0/531/420/31
Cardiac failure congestiveCardiac disorders1/530/420/31
Febrile neutropeniaBlood and lymphatic system disorders1/530/420/31
HyperglycaemiaMetabolism and nutrition disorders1/530/420/31
MastitisInfections and infestations1/530/420/31
MetastasisNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/530/420/31
PneumoniaInfections and infestations1/530/420/31
Most frequent other events
Showing 10 of 63
Most frequent other events
EventCohort A: Triple-negative Breast CancerCohort B: ER/PR Positive/HER2-negative Breast CancerCohort C: HER2 Positive Breast Cancer
FatigueGeneral disorders33/5226/4223/31
Peripheral Sensory NeuropathyNervous system disorders24/5225/4216/31
Neutrophil Count DecreasedInvestigations26/5221/4217/31
LeukopeniaInvestigations15/5223/4212/31
AnemiaBlood and lymphatic system disorders20/5213/4216/31
NauseaGastrointestinal disorders18/5216/4214/31
ArthralgiaMusculoskeletal and connective tissue disorders20/528/4212/31
ConstipationGastrointestinal disorders14/5213/429/31
MyalgiaMusculoskeletal and connective tissue disorders13/529/429/31
HeadacheNervous system disorders11/5212/425/31

Baseline characteristics

All patients who receive at least one dose of treatment.

Age, Continuous
Age, Continuous(years)Cohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast Cancer PatientsCohort C: HER2-positive Breast Cancer PatientsTotal
Median49 (28 to 74)55 (27 to 71)52 (38 to 78)52 (27 to 78)
Sex: Female, Male
Sex: Female, Male(Participants)Cohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast Cancer PatientsCohort C: HER2-positive Breast Cancer PatientsTotal
Female534231126
Male0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast Cancer PatientsCohort C: HER2-positive Breast Cancer PatientsTotal
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American124218
White393728104
More than one race0000
Unknown or Not Reported2114
Region of Enrollment
Region of Enrollment(Participants)Cohort A: Triple-negative Breast Cancer PatientsCohort B: ER/PR Positive/HER2-negative Breast Cancer PatientsCohort C: HER2-positive Breast Cancer PatientsTotal
United States534231126
08

Study locations

18 sites
  • Florida Cancer Specialists North
    Fort Myers, Florida 33916, United States
  • Florida Cancer Specialists South
    Fort Myers, Florida 33916, United States
  • Watson Clinic Center for Cancer Care and Research
    Lakeland, Florida 33805, United States
  • Florida Hospital Cancer Insitute
    Orlando, Florida 32804, United States
  • Northeast Georgia Medical Center
    Gainesville, Georgia 30501, United States
  • Providence Medical Group
    Terre Haute, Indiana 47802, United States
  • Mercy Hospital
    Portland, Maine 04101, United States
  • Center for Cancer and Blood Disorders
    Bethesda, Maryland 20817, United States
  • National Capital Clinical Research Consortium
    Bethesda, Maryland 20817, United States
  • Nebraska Methodist Cancer Center
    Omaha, Nebraska 68114, United States
  • Atlantic Health System
    Morristown, New Jersey 07960, United States
  • Hematology Oncology Associates of Northern NJ
    Morristown, New Jersey 07960, United States
  • Oncology Hematology Care, Inc.
    Cincinnati, Ohio 45242, United States
  • South Carolina Oncology Associates
    Columbia, South Carolina 29210, United States
  • Chattanooga Oncology Hematology Associates
    Chattanooga, Tennessee 37404, United States
  • Tennessee Oncology
    Nashville, Tennessee 37203, United States
  • Texas Health Physician Group
    Arlington, Texas 76011, United States
  • The Center for Cancer and Blood Disorders
    Fort Worth, Texas 76104, United States
09

References and documents

Publications

  • Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1275-81. doi: 10.1200/JCO.2007.14.4147. Epub 2008 Feb 4. PubMed 18250347 ↗
  • Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Dieras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. doi: 10.1016/S0140-6736(11)60070-6. Epub 2011 Mar 2. PubMed 21376385 ↗
  • Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 2001 Feb 1;61(3):1013-21. PubMed 11221827 ↗

Study documents

  • Study protocol · Mar 20, 2013
  • Statistical analysis plan · Apr 3, 2018

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 15, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01401959
Lead sponsor
SCRI Development Innovations, LLC
Collaborators
Eisai Inc.
Responsible party
Sponsor
First posted
Jul 26, 2011
Start date
Sep 23, 2011
Primary completion
Apr 3, 2017
Completion
Apr 3, 2017
Results posted
May 7, 2018
Last update
Jun 15, 2018

Study contacts

Denise A Yardley, M.D.
study chair · SCRI Development Innovations, LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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