Eribulin Mesylate or Paclitaxel as First- or Second-Line Therapy in Treating Patients With Recurrent Stage IIIC-IV Breast Cancer
Condition: Breast Adenocarcinoma; HER2/Neu Negative; Invasive Breast Carcinoma; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7
MeSH terms: Breast Neoplasms
Intervention: Eribulin Mesylate; Laboratory Biomarker Analysis; Paclitaxel; Quality-of-Life Assessment
Intervention description: Given IV; Correlative studies; Given IV; Ancillary studies
Intervention MeSH terms: Paclitaxel; Halichondrin B; Albumin-Bound Paclitaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 201.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies how well eribulin mesylate or paclitaxel work as
      first- or second-line therapy in treating patients with stage IIIC-IV breast cancer that has
      come back. Drugs used in chemotherapy, such as eribulin mesylate and paclitaxel, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent document signed and dated by patient

          -  Histologic confirmation of invasive adenocarcinoma originating in the breast

          -  Stage IV disease or stage IIIC disease (using the 7th edition American Joint Committee
             on Cancer [AJCC] criteria) not amenable to local therapy

          -  Clinical or radiographic evidence of disease progression

          -  Documentation of HER2 negative breast cancer at the time of protocol registration;
             (Note: HER2 negativity is defined as 0 or 1+ by immunohistochemistry OR nonamplified
             or equivocal by fluorescence in situ hybridization [FISH]; status may be defined on
             the basis of historic results on the breast primary or a metastatic site, whichever is
             most recent; repeat biopsies are not required for participation in this protocol)

          -  Known hormone receptor status at the time of protocol registration; (Note: estrogen
             receptor [ER] and/or progesterone receptor [PgR] status are considered positive with a
             cut-off of >= 1% invasive tumor cells; status may be defined on the basis of historic
             results on the breast primary or a metastatic site, whichever is most recent; repeat
             biopsies are not required for participation in this protocol)

          -  Patients must demonstrate resolution of all toxicities related to prior chemotherapy,
             endocrine therapy, targeted therapy, or biologic therapy to grade =< 1, including
             peripheral neuropathy, with the exception of alopecia (any grade permissible)

          -  No more than one prior chemotherapy regimen for advanced or metastatic breast cancer
             is allowed; prior chemotherapy for metastatic disease must have been completed >= 14
             days prior to randomization

               -  Any single agent therapy, and any combination of cytotoxic, endocrine, biological
                  targeted agents, and/or humanized antibodies, scheduled to be administered as a
                  preplanned treatment, given concomitantly, sequentially or both, is considered
                  one regimen

               -  Planned neoadjuvant chemotherapy and postoperative adjuvant chemotherapy is
                  considered one regimen

               -  If the dosing of one or more of the chemotherapy components of a regimen must be
                  reduced for toxicity, the modified version of the original regimen is not
                  considered a new regimen

               -  If one or more of the chemotherapy components of a regimen must be omitted for
                  toxicity, the modified version of the original regimen is not considered a new
                  regimen

               -  If one of the chemotherapy components of a regimen must be replaced with another
                  similar drug of the same therapeutic class, the modified version of the original
                  regimen is not considered a new regimen; however, if a new component, dissimilar
                  to any of the original components, is added to the regimen, the modified version
                  is considered a new regimen

               -  If chemotherapy is interrupted for surgery or radiotherapy and then continues
                  with an unchanged schedule and components, treatment is considered as one regimen
                  despite the interruption

          -  Prior treatment may include a taxane as per the following criteria:

               -  Prior taxane (including paclitaxel) in the adjuvant or neoadjuvant setting is
                  allowed, provided that the interval between the completion of (neo)adjuvant
                  therapy and disease recurrence is > 12 months

               -  Prior taxane in the metastatic setting is allowed, provided that the agent
                  administered in the metastatic setting was not standard paclitaxel

          -  Any number of prior endocrine therapies is allowed and must be discontinued prior to
             randomization

          -  Any number of biologic therapies (e.g., bevacizumab) or immunotherapies is allowed in
             the absence of co-administered chemotherapy and must have been completed >= 28 days
             prior to randomization

          -  Prior treatment with an investigational agent is allowed but must have been completed
             >= 28 days prior to randomization with resolution of all treatment-related toxicities
             to grade =< 1.

          -  Minor surgical procedures must be completed >= 7 days prior to randomization with
             documentation of adequate recovery from associated complications to grade =< 1; these
             include (but are not limited to) laparoscopy, thoracoscopy, bronchoscopy,
             mediastinoscopy, endoscopic ultrasonography, skin biopsy, percutaneous needle biopsy,
             and routine dental procedures; as a precautionary measure, it is recommended, but not
             strictly required, that placement of a central venous access device, thoracentesis, or
             paracentesis be done 7 days before the initiation of protocol directed chemotherapy
             with documentation of adequate recovery from associated complications to grade =< 1

          -  Major surgical procedures and open biopsies must be completed >= 28 days prior to
             randomization with documentation of adequate recovery from associated complications to
             grade =< 1

          -  Prior radiotherapy must be completed >= 14 days prior to randomization with
             documentation of adequate recovery from associated toxicities to grade =< 1

          -  Treatment with bisphosphonates or denosumab is allowed and recommended per the
             standard of care

          -  Therapeutic anticoagulation is allowed for patients on a stable dose of warfarin or
             low molecular weight heparin

          -  Measurable disease is defined as at least one lesion that can be accurately measured
             with the longest diameter as >= 1.0 cm by computed tomography (CT) scan or >= 1.0 cm
             with calipers by clinical examination; the exceptions to these criteria are pathologic
             lymph nodes, which must be >= 1.5 cm in the short axis when assessed by CT scans with
             slice thickness =< 0.5 cm

          -  Non-measurable lesions include the following: small lesions (longest diameter < 1.0 cm
             for all lesions other than pathologic lymph nodes, which are >= 1.0 cm and < 1.5 cm in
             the short axis), bone metastases, pleural effusions, pericardial effusions, ascites,
             inflammatory breast disease, leptomeningeal disease, lymphangitis pulmonis,
             lymphangitis cutis, and abdominal masses not followed by CT or magnetic resonance
             imaging (MRI)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Life expectancy of > 12 weeks

          -  Patients with a history of resected brain metastases are eligible only if they are
             asymptomatic and have stable MRI scans for 3 consecutive months, including =< 28 days
             of study registration

          -  Patients who receive stereotactic radiosurgery or whole brain radiation for brain
             metastases are eligible only if they are asymptomatic and have stable MRI scans for 3
             consecutive months, including =< 28 days of study registration

          -  Obtained =< 7 days prior to registration: Absolute neutrophil count >= 1500/uL

          -  Obtained =< 7 days prior to registration: Platelet count >= 100,000/uL

          -  Obtained =< 7 days prior to registration: Hemoglobin >= 9 g/dL

          -  Obtained =< 7 days prior to registration: Total bilirubin =< 1.5 times the upper limit
             of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert?s syndrome

          -  Obtained =< 7 days prior to registration: Serum glutamic-oxaloacetic transaminase
             (SGOT) (aspartate aminotransferases [AST]) and serum glutamate pyruvate transaminase
             (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN except in the case of liver
             metastases, where =< 5 x ULN is allowed

          -  Obtained =< 7 days prior to registration: Creatinine =< 2.0 mg/dL or creatinine
             clearance > 50 mL/min

          -  Obtained =< 7 days prior to registration: Corrected QT (QTc) interval =< 500 msec on
             the baseline electrocardiogram

          -  Negative pregnancy test done =< 72 hours prior to registration for women of
             childbearing potential only; Note: all female subjects will be considered to be of
             child-bearing potential unless they are postmenopausal (at least 12 months consecutive
             amenorrhea, in the appropriate age group and without other known or suspected cause),
             or have been sterilized surgically (i.e., bilateral tubal ligation >= 1 menstrual
             cycle prior to randomization, or have undergone a hysterectomy and/or bilateral
             oophorectomy)

               -  Female subjects of child-bearing potential must agree to use highly effective
                  contraception during the study treatment and for 3 months after the final dose of
                  study treatment; female subjects exempt from this requirement are subjects who
                  practice total abstinence; if currently abstinent, the subject must agree to use
                  a double barrier method of contraception (i.e., condom and occlusive cap
                  [diaphragm or cervical/vault caps]) with spermicide or until they are established
                  on highly effective contraception for at least one menstrual cycle if they become
                  sexually active during the study treatment and for 3 months after the final dose
                  of study treatment

               -  Highly effective contraception includes:

                    -  Placement of intrauterine device or system

                    -  Barrier methods of contraception: condom or occlusive cap (diaphragm or
                       cervical/vault cap) with spermicide

                    -  Vasectomized partner with confirmed azoospermia

               -  Male subjects and their female partner who are of child-bearing potential (as
                  defined above), and are not practicing total abstinence, must agree to use highly
                  effective contraception during study treatment and for 3 months after the final
                  dose of study treatment; if currently abstinent, the subject must agree to use a
                  double barrier method of contraception if they become sexually active, or until
                  they are established on highly effective contraception as described above

          -  Ability to complete questionnaire(s) independently or with assistance

          -  Willingness to provide blood and tissue samples for correlative research purposes;
             (Note: these tissue samples are from archived tissue, if available; new biopsies are
             not required)

          -  Ability to comprehend and respond to questions using a telephone keypad

        Exclusion Criteria:

          -  Prior malignancy, other than carcinoma in situ of the cervix and non-melanoma skin
             cancers, unless the prior malignancy was diagnosed and definitively treated >= 5 years
             previously, there is no subsequent evidence of recurrence, and the patient is
             considered by a physician to be at < 30% risk of relapse

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Presence of a serious nonhealing wound, ulcer, or bone fracture

          -  History of Common Terminology Criteria for Adverse Events (CTCAE) grade >= 3
             hypersensitivity to paclitaxel or Cremophor EL

          -  Pre-existing peripheral neuropathy grade ?= 2 at registration

          -  Significant cardiovascular impairment (e.g., New York Heart Association congestive
             heart failure of grade II or above, unstable angina, myocardial infarction within the
             past 6 months, or serious cardiac arrhythmia)

          -  Subjects with known positive human immunodeficiency virus (HIV) status

          -  History of stroke or transient ischemic attack =< 6 months prior to registration

          -  History of uncontrolled seizures; (Note: patients are eligible for the study if the
             seizures are well controlled with standard medications)

          -  Severe or uncontrolled intercurrent illness/infection

          -  Concurrent administration of any other investigational agent considered to have
             potential efficacy in the treatment of breast cancer

          -  Prior exposure to eribulin mesylate