Clinical trial NCT01827787: Eribulin in HER2 Negative Metastatic BrCa
Official title: A Phase 2 Study of Eribulin in Patients With HER2-Negative, Metastatic Breast Cancer: Evaluation of Efficacy, Toxicity and Patient-Reported Outcomes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: metastatic breast cancer
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2013-04-10
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 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)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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.
measure: Time to First Response (TTR)
timeFrame: 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).
measure: Duration of Overall Response (DOR)
timeFrame: 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.
measure: Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Sensory Neuropathy
timeFrame: 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)
measure: Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Motor Neuropathy
timeFrame: 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)
measure: Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline
timeFrame: Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11
measure: Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline
timeFrame: Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11
Other outcomes:
Locations:
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Dana-Farber Cancer Institute at Faulkner Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Milford
country: United States
facility: DF/BWCC at Milford Regional Cancer Center
state: Massachusetts
city: Weymouth
country: United States
facility: South Shore Hospital
state: Massachusetts
city: Londonderry
country: United States
facility: Dana-Farber/New Hampshire Oncology-Hematology
state: New Hampshire
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Erica Mayer, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Filho OM, Giobbie-Hurder A, Lin NU, Faggen M, Come S, Openshaw T, Constantine M, Walsh J, Freedman RA, Schneider B, Burstein HJ, Mayer EL. A dynamic portrait of adverse events for breast cancer patients: results from a phase II clinical trial of eribulin in advanced HER2-negative breast cancer. Breast Cancer Res Treat. 2021 Jan;185(1):135-144. doi: 10.1007/s10549-020-05928-4. Epub 2020 Oct 6.