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A Phase 2 Study of Eribulin Followed by AC as Preoperative Therapy for HER2-negative Inflammatory 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02623972
Recruitment Status : Recruiting
First Posted : December 8, 2015
Last Update Posted : September 2, 2020
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Beth Overmoyer MD, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE December 2, 2015
First Posted Date  ICMJE December 8, 2015
Last Update Posted Date September 2, 2020
Actual Study Start Date  ICMJE December 30, 2015
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2015)
Pathologic Complete Response [ Time Frame: 112 Days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2019)
  • Disease Free Survival [ Time Frame: 2 years ]
  • Time to Treatment Failure [ Time Frame: 2 years ]
  • Overall Survival [ Time Frame: 2 Years ]
  • Pathologic disease response at mastectomy will be reported as "residual disease burden (RCB)". [ Time Frame: 2 Years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2015)
  • Disease Free Survival [ Time Frame: 2 years ]
  • Time to Treatment Failure [ Time Frame: 2 years ]
  • Overall Survival [ Time Frame: 2 Years ]
  • Pathologic disease response at mastectomy will be reported as "residual disease burden (RCB)". [ Time Frame: 2 Years ]
  • RT-qPCR assessment of gene expression of 10-EMT-related genes and 15-genes involved in modulating vessel phenotype or EC-PVC interactions will be compared following treatment with eribulin. [ Time Frame: 2 Years ]
    The paired expression levels of each gene at the two time points will be summarized graphically and descriptively. Wilcoxon signed rank test will be used to determine if there are any significant changes in the expression level of each gene and the clinical outcome of pCR, DFS, OS, RCB.
  • To correlate changes in imaging (Ktrans ve, vp, and initial area under the curve (iAUC)) with genomic changes determined on core biopsies of the breast sampled at the same time points. [ Time Frame: 2 Years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2 Study of Eribulin Followed by AC as Preoperative Therapy for HER2-negative Inflammatory Breast Cancer
Official Title  ICMJE A Phase 2 Study of Eribulin Followed by Doxorubicin and Cyclophosphamide as Preoperative Therapy for HER2-negative Inflammatory Breast Cancer
Brief Summary This research study is studying a drug called eribulin combined with standard treatment as a possible preoperative treatment for HER2 negative inflammatory 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.

Eribulin works by interfering with cancer cell division, growth, and spread.

The goal of this research study is to evaluate inflammatory breast cancer's response to treatment with eribulin followed by AC chemotherapy (Cohort A) and also the response to treatment with AC followed by Eribulin (Cohort B) when given as a preoperative chemotherapy treatment for participants with HER2 negative inflammatory breast cancer.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Inflammatory Breast Cancer
  • Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
Intervention  ICMJE
  • Drug: Eribulin
    administered IV for 4 cycles
    Other Names:
    • Halaven
    • B1939 mesylate
  • Drug: Adriamycin
    administered IV with cyclophosphamide for 4 cycles
    Other Name: Doxorubicin
  • Drug: Cyclophosphamide
    administered IV with adriamycin for 4 cycles
    Other Names:
    • Cytoxan®
    • Neosar®
Study Arms  ICMJE
  • Experimental: Arm A: Eribulin > AC
    • Eribulin-Administered via iv, at predetermined dosage and schedule per cycle
    • Two research breast biopsies
    • Adriamycin (doxorubicin) via iv a predetermined dosage and schedule per cycle
    • Cyclophosphamide (AC) via iv a predetermined dosage and schedule per cycle
    • Surgical Removal of the breasts (Mastectomy) and axillary lymph node dissection
    • Radiation Therapy
    • Endocrine Therapy (if applicable)
    • Optional 5 Patient-Optional DCE-MRI (Dynamic Contrast Enhanced-Magnetic Resonance Imaging) scans
    Interventions:
    • Drug: Eribulin
    • Drug: Adriamycin
    • Drug: Cyclophosphamide
  • Experimental: Arm B: AC > Eribulin
    • Adriamycin (doxorubicin) via iv a predetermined dosage and schedule per cycle
    • Cyclophosphamide (AC) via iv a predetermined dosage and schedule per cycle
    • Two research breast biopsies
    • Eribulin-Administered via iv, at predetermined dosage and schedule per cycle
    • Surgical Removal of the breasts (Mastectomy) and axillary lymph node dissection
    • Radiation Therapy
    • Endocrine Therapy (if applicable)
    • Optional 5 Patient-Optional DCE-MRI (Dynamic Contrast Enhanced-Magnetic Resonance Imaging) scans
    Interventions:
    • Drug: Eribulin
    • Drug: Adriamycin
    • Drug: Cyclophosphamide
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 20, 2019)
32
Original Estimated Enrollment  ICMJE
 (submitted: December 3, 2015)
25
Estimated Study Completion Date  ICMJE February 2023
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

-Participants must have histologically confirmed invasive breast cancer. All histologic subtypes are eligible.

-- Patients must NOT have HER2 positive status based on ASCO/CAP guidelines defined as: IHC 3+ based on circumferential membrane staining that is complete, intense and/or

FISH positive based on one of the three following criteria:

Single-probe average HER2 copy number ≥ 6.0 signals/cell; OR Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number ≥ 6.0 signals/cell; OR Dual-probe HER2/CEP17 ratio ≥2.0

  • Age ≥18 years. Because no dosing or adverse event data are currently available on the use of eribulin in participants <18 years of age, children are excluded from this study
  • ECOG performance status ≤1 (Karnofsky ≥70%)
  • Participants must have normal organ and marrow function as defined below:

    • leukocytes ≥3,000/mcL
    • absolute neutrophil count ≥1,500/mcL
    • platelets ≥100,000/mcL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine ≤1.5 × institutional upper limit of normal

      --- OR

    • creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • Patients must have the clinical diagnosis of inflammatory breast cancer.
  • Patients must be without evidence of visceral or bone involvement with metastatic cancer on physical exam or any diagnostic study. Extensive nodal involvement (distant or regional) is allowed.
  • LVEF > 50% calculated by echocardiogram (ECHO)
  • Patients may have bilateral breast cancer so long as one breast meets criteria for inflammatory breast cancer, and the breast with inflammatory breast cancer has never received prior therapy.
  • The effects of eribulin on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of chemotherapy administration.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Both men and women of all races and ethnic groups are eligible for this trial. Because breast cancer predominantly affects females, it is anticipated that male enrollment will be < 5% of the overall study population.

Exclusion Criteria:

  • Participants who are receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to eribulin or other agents used in study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because eribulin is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with eribulin, breastfeeding should be discontinued if the mother is treated with eribulin. These potential risks may also apply to other agents used in this study.
  • HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with eribulin. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • A baseline corrected QT interval of > 470 ms.
  • Individuals with a history of a different 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 3 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 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
  • Patients may not have received eribulin, paclitaxel, doxorubicin, or cyclophosphamide as anti-neoplastic 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: Beth Overmoyer, MD 617-632-6157
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02623972
Other Study ID Numbers  ICMJE 15-292
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Beth Overmoyer MD, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE Eisai Inc.
Investigators  ICMJE
Principal Investigator: Beth Overmoyer, MD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date July 2020

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