Phase II Study of Eribulin Mesylate, Trastuzumab, and Pertuzumab in Women With Metastatic, Unresectable Locally Advanced, or Locally Recurrent HER2-Positive Breast Cancer

Stopped early · Phase 2

Conditions studied: HER2-positive Breast Cancer, Metastatic Breast Cancer

In brief

In this study, the investigators are testing the effectiveness of the combination of eribulin, pertuzumab and trastuzumab to learn whether this combination of drugs works in treating advanced HER2-positive breast cancer that had received at least one prior treatment previously. At this point, the standard treatment for HER2-positive cancer that has progressed (grown) after a first treatment is chemotherapy combined with therapies that target the HER2 protein (e.g., trastuzumab or lapatinib).

Key facts

Study ID: NCT01912963
Run by: Dana-Farber Cancer Institute
People needed: 32
Starts: 2013-09-01
Expected to finish: 2016-12-01
Last updated by the study team: 2018-12-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Participants must meet the following criteria on screening examination to be eligible to participate in the study:
Participants must have invasive primary tumor or metastatic tissue confirmation of human epidermal growth factor receptor 2 (HER2)-positive status, defined as presence of one or more of the following criteria: Over-expression by immunohistochemistry (IHC) with score of 3+ AND/OR HER2 gene amplification (> 6 HER2 gene copies per nucleus or a FISH ratio [HER2 gene copies to chromosome 17 signals] of ≥ 2.0) Note: Participants with a negative or equivocal overall result (FISH ratio of <2.0 or ≤ 6.0 HER2 gene copies per nucleus) and IHC staining scores of 0, 1+, 2+ are not eligible for enrollment.
Participants must have metastatic, unresectable locally advanced, or locally recurrent HER2-positive breast cancer. For the phase II portion of the study, it is required that participants have measurable disease, as defined by RECIST 1.1, which can be accurately evaluated on computerized tomography (CT) or magnetic resonance (MRI). Measurable disease is defined as: at least one lesion of >10 mm in the longest diameter for a non-lymph node or >15 mm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1.criteria.1
Participants must have received at least 1 line of chemotherapy for advanced or metastatic breast cancer and/or relapse/progressed while on or within 6 months of completion of neoadjuvant or adjuvant trastuzumab. Prior pertuzumab is allowed in the phase II portion of the trial.
Participants must have had prior trastuzumab therapy (either in the adjuvant or metastatic setting).
Participants must be at least 2 weeks out from prior endocrine therapy, chemotherapy,radiotherapy, or other cancer-directed therapy (including novel agents), with adequate recovery of toxicity to baseline, or grade ≤1, with the exception of alopecia and hot flashes. Participants may have initiated bisphosphonate/denosumab therapy prior to start of protocol therapy. Biphosphonate/denosumab therapy may continue during protocol treatment. Such participants will have bone lesions considered evaluable for progression. Washout for trastuzumab is not necessary.
Women and men, age 18 years at the time of informed consent.
Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 or a Karnofsky Performance Scale (KP) 70%.
Participants must have normal organ and marrow function as defined below:
Absolute neutrophil count > 1,500/mcL
Platelets > 75,000/mcL
Hemoglobin >9g/dl
Total bilirubin ≤2.0 X institutional upper limit of normal
Aspartate Aminotransferase (AST, SGOT)/ALT(Alanine Aminotransferase, SGPT) ≤ 3 X institutional ULN without liver metastases, or ≤ 5 times institutional upper limit normal (ULN) with liver metastases (if liver metastases felt to be cause of Liver function tests (LFT) abnormalities)
Alkaline phosphatase (ALP) ≤3 x institutional upper limit of normal If total ALP is >3x institutional upper limit normal (in the absence of liver metastasis) or >5x institutional upper limit of normal (in subjects with liver metastasis) AND the subject is known to have bone metastases, then liver ALP isoenzyme should be used to assess liver function rather than total ALP.
Creatinine 2.0 mg/dL or creatinine clearance ≥50 mL/min.
left ventricular ejection fraction (LVEF) ≥50%, as determined by radionucleoventilugrams (RVG) (multi-gated acquisition-MUGA) or Echocardiogram (ECHO) within 60 days prior to initiation of protocol therapy.
Adequate IV access
The effects of eribulin mesylate, trastuzumab, and pertuzumab on the developing human fetus are unknown. Pre-clinical data was suggestive of a teratogenic effect of eribulin mesylate. Pertuzumab caused oligohydramnios, delayed renal development and embryo-fetal deaths in pregnant cynomolgus monkeys. In the post-marketing setting, cases of oligohydramnios, some associated with fatal pulmonary hypoplasia of the fetus have been reported in pregnant women receiving trastuzumab. For these reasons 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 participating in this study, she should inform her treating physician immediately.
Ability to understand and willingness to sign a written informed consent document (approved by Institutional review board or independent ethics committee) obtained prior to any study procedure, with the understanding that the subject may withdraw at any time without prejudice.
Laboratory tests required for eligibility must be completed within 14 days prior study entry. Baseline tumor measurements must be documented from tests within 28 days of study entry. Other non-laboratory tests must be performed within 28 days of study entry.
For the Phase 2 portion of the study; patients must have tissue that is amenable to biopsy and must be willing to undergo research biopsy.
Exclusion Criteria: - Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
Participants receiving any other study agents.
Participants receiving any other cancer directed concurrent therapy; such as concurrent chemotherapy, radiotherapy, or hormonal therapy. Concurrent treatment with biphosphonates/denosumab is allowed but should be started before starting treatment on study.

Where it is running

Massachusetts General Hospital — Boston, Massachusetts, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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