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Eribulin in HER2 Negative Metastatic BrCa

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: NCT01827787
Recruitment Status : Completed
First Posted : April 10, 2013
Results First Posted : February 6, 2019
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Erica Mayer, MD, MPH, Dana-Farber Cancer Institute

Brief Summary:
Improvements in outcomes with metastatic breast cancer (MBC) have been observed in the last 30 years, however, overall prognosis remains poor with median survival of 2 to 3 years. Long term complete responses are observed only for a minority of MBC patients (2-5%) and MBC remains an incurable disease for most patients. Eribulin is a chemotherapy approved by the US FDA in November of 2010 to treat patients with MBC who have received at least two prior chemotherapy regimens. In this research study, the investigators are looking to see how well eribulin helps participants with MBC in an earlier-line setting. Eribulin works by interfering with cancer cell division, growth and spread.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Eribulin Phase 2

Detailed Description:
Based on positive results in heavily pre-treated MBC patients, eribulin is being studied as first-line or second-line chemotherapy treatment. This is a non-randomized, open label study with participants enrolled in one of two cohorts: Cohort 1. Hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) or Cohort 2: Triple negative breast cancer (TNBC) meaning HR-negative/HER2-negative (HR-/HER2-). HR- means progesterone receptor-negative (PR-) and estrogen receptor-negative (ER-). Beyond efficacy as measured primarily by response to treatment, investigators will evaluate safety, tolerability and quality of life. In particular, it is hypothesized that eribulin may have lower rates of neuropathy, a common side effect of many of the major chemotherapeutics with activity in MBC. The investigators will study the effect eribulin has on the nerves through regular questionnaires that ask about any nerve-related symptoms. The investigators also plan to send blood samples to explore if gene markers may indicate increased sensitivity to the nerve effects of eribulin.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 83 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is not a randomized trial rather participants are enrolled based on disease histology. Participants in each arm receive the same treatment regimen.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Eribulin in Patients With HER2-Negative, Metastatic Breast Cancer: Evaluation of Efficacy, Toxicity and Patient-Reported Outcomes
Actual Study Start Date : May 2013
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Cohort 1: HR+/HER2-

Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle

Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.

Drug: Eribulin
Other Names:
  • E7389
  • Halaven
  • ER-086526
  • NSC-707389

Experimental: Cohort 2: TNBC

Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle

Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.

Drug: Eribulin
Other Names:
  • E7389
  • Halaven
  • ER-086526
  • NSC-707389




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2) ]
    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.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) PFS follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2. ]
    PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum longest diameter (LD), taking as reference the smallest sum on study with at least 5 mm absolute increase or the appearance of one or more new lesions. For non-target lesions, PD is appearance of one or more new lesions or unequivocal progression of existing non-target lesions.

  2. Time to First Response (TTR) [ Time Frame: Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). ]
    TTR is defined as the time from first dose of study treatment until the earliest date that complete response (CR) or partial response (PR) based on RECIST 1.1 criteria is objectively documented. Non-CR, non-PR participants are censored at date of last disease assessment. 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 requires 4 week or later confirmation and assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  3. Duration of Overall Response (DOR) [ Time Frame: Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) DOR follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2. ]
    DOR is defined as the that response criteria for CR or PR (whichever is recorded first) are first met until the date that PD or death from any cause is first objectively documented. Participants who do not have PD will be censored on date of last disease assessment.

  4. Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Sensory Neuropathy [ Time Frame: Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2) ]
    The percentage of treated participants experiencing grade 1-3 peripheral sensory neuropathy with treatment attribution of possible, probable or definite based on Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.

  5. Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Motor Neuropathy [ Time Frame: Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2) ]
    TThe percentage of treated participants experiencing grade 1-3 peripheral motor neuropathy with treatment attribution of possible, probable or definite based on Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.

  6. Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline [ Time Frame: Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11 ]
    The FACT-BCS is a validated, self-administered questionnaire which captures quality of life (QOL) concerns specific to breast cancer patients. (Brady MJ, et al. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument. JCO 1997; 15:974-86). The FACT-BCS has 9-items scored on a 5-point Likert scale (Not at all, A little bit, Somewhat, Quite a bit, Very much) with a maximum score of 36. A higher score indicates better QOL. A minimal clinically important difference is 3-5 points.

  7. Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline [ Time Frame: Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11 ]
    The FACT-Ntx is a validated, self-administered questionnaire which captures quality of life (QOL) concerns specific to patients suffering from neurotoxicity. (Calhoun EA, et al. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 2003; 13:741-8). The FACT-Ntx has 11-items scored on a 5-point Likert scale (Not at all, A little bit, Somewhat, Quite a bit, Very much) with a maximum score of 44. A higher score indicates better QOL. A minimal clinically important difference is 3-5 points.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Histologically or cytologically proven invasive breast cancer, locally recurrent or metastatic, with at least one measureable lesion according to RECIST v1.1
  • Hormone receptor positive or hormone receptor negative HER2-negative disease
  • Up to one prior line of chemotherapy for advanced disease is allowed (discontinued at least 14 days prior to initiation of protocol therapy)
  • Prior bevacizumab in the neo/adjuvant or metastatic setting is acceptable
  • No limit on prior lines of endocrine therapy, but must be discontinued at least 7 days prior to initiation of protocol therapy
  • Must have completed any prior radiotherapy at least 2 weeks prior to initiation of protocol therapy
  • Must have recovered from reversible effects of prior therapies to no more than grade 1 toxicity, with the exception of alopecia
  • Agree to use adequate contraception for the duration of study participation

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Prior treatment with eribulin
  • Prior malignancy other than carcinoma in situ of the cervix or nonmelanoma skin cancer unless diagnosed and definitively treated at least 3 years before enrollment in this study
  • Clinically significant cardiovascular impairment
  • Active brain metastases or unevaluated neurologic symptoms suggestive of brain metastases
  • Pulmonary dysfunction requiring the use of oxygen
  • Prior organ allograft requiring immunosuppression
  • HIV positive on combination antiretroviral therapy
  • Pre-existing grade 3 or 4 neuropathy
  • Hypersensitivity to halichondrin B or halichondrin B chemical derivative
  • Uncontrolled intercurrent illness
  • Inability to read in English

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): NCT01827787


Locations
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United States, Maine
Eastern Maine Medical Center
Bangor, Maine, United States, 04402
United States, Massachusetts
Dana-Farber Cancer Institute at Faulkner Hospital
Boston, Massachusetts, United States, 02130
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
DF/BWCC at Milford Regional Cancer Center
Milford, Massachusetts, United States, 01757
South Shore Hospital
Weymouth, Massachusetts, United States, 02190
United States, New Hampshire
Dana-Farber/New Hampshire Oncology-Hematology
Londonderry, New Hampshire, United States, 03053
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
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Principal Investigator: Erica Mayer, MD, MPH Dana-Farber Cancer Institute
  Study Documents (Full-Text)

Documents provided by Erica Mayer, MD, MPH, Dana-Farber Cancer Institute:

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Responsible Party: Erica Mayer, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01827787    
Other Study ID Numbers: 13-077
First Posted: April 10, 2013    Key Record Dates
Results First Posted: February 6, 2019
Last Update Posted: February 6, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Erica Mayer, MD, MPH, Dana-Farber Cancer Institute:
metastatic breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases