| Eligibility |
Inclusion Criteria:
- Male or female >= 18 years of age
- Is willing and able to provide written informed consent for the trial
- Has histological confirmation of breast carcinoma with a clinical diagnosis of IBC
based on the presence of inflammatory changes in the involved breast, including
diffuse erythema and edema (peau d'orange), with or without an underlying palpable
mass involving the majority of the skin of the breast. Or the diagnosis confirmed by
the MD Anderson IBC specialists. Pathological evidence of dermal lymphatic invasion
should be noted but is not required for the diagnosis of IBC
- Any prior treatments will be allowed except eribulin and/or any EP2/4 inhibitor
- Has at least 2 weeks of untreated period from the previous treatment
- Any receptor status for ER/PR and HER2. But for HER2+ type, must has failed
trastuzumab, pertuzumab, and T-DM1 treatment.
- NOTE: HER2 positive status is defined as strongly positive (3+) staining score by
immunohistochemistry (IHC), or gene amplification using fluorescence in situ
hybridization (FISH), if performed. If IHC is equivocal (2+). HER2 negative
status, which is determined by assays using IHC require negative (0 or 1+)
staining score. If IHC is equivocal (2+) staining score
- Has a measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
version (v)1.1 (only applies to phase II part)
- NOTE: Measurable disease: Measurable lesions are defined as those that can be
accurately measured in at least one-dimension (longest diameter to be recorded)
as >= 20 mm by chest X-ray, >= 10 mm by computed tomography (CT) scan, >= 10 mm
with calipers by clinical exam. Measurable malignant lymph nodes: To be
considered pathologically enlarged and measurable, a lymph node must be >= 15mm
in short axis when assessed by CT scan. Non-measurable disease: All other lesions
(or sites of disease), including small lesions, are considered non-measurable.
Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions,
lymphangitis, cutis/pulmonitis, inflammatory breast disease, and abdominal masses
(not followed by CT or magnetic resonance imaging [MRI]) are considered
non-measurable
- Has a distant metastasis site or locoregional recurrence
- Is willing to provide fresh tumor tissue via tumor biopsy before the first dose of the
study drug only if participant has a disease can be be safely accessed through a
CT-guided/ultrasound (US)-guided or percutaneous biopsy for multiple core biopsies
judged by the investigator. If participant doesn't have a disease that can be safely
accessed, they are still eligible
- Performance status (PS) of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG)
performance scale
- Absolute neutrophil count (ANC) >= 1,200 /mcL
- Platelets >= 100,000 /mcL
- Hemoglobin (Hgb) >= 9 g/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (up to =< 3 x ULN for patients
with liver metastasis)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (up
to =< 5 x ULN for patients with liver metastasis)
- Cockcroft-Gault glomerular filtration rate (GFR) (mL/min/1.73 m^2) >= 50
- Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram (ECHO) or
multigated acquisition (MUGA) scan
- Female patients must not be pregnant or breastfeeding and must be practicing a
medically acceptable form of locally approved birth control, be sterile or
post-menopausal. Male patients should be using a medically acceptable form of birth
control during the trial or be sterile
- Female patient: A female patient is eligible to participate if she is not
pregnant, not breastfeeding, and at least one of the following conditions
applies:
- Not a woman of childbearing potential (WOCBP) OR
- A WOCBP agrees to follow the contraceptive guidance during the treatment
period and at least 6 months after the last dose of trial intervention and
must refrain from breastfeeding for at least 2 months after the last
grapiprant treatment
- WOCPB must have a negative urine pregnancy test no more than 7 days prior to
starting treatment on-study
- Male patients: A male patient must agree to use contraception during the
treatment period and for at least 6 months after the last grapiuprant treatment
and refrain from donating sperm during this period
- Patient with human immunodeficiency virus (HIV) including current or prior infection
would be included if:
- With CD4+ T-cell (CD4+) counts >= 350 cells/uL
- Without a history of acquired immunodeficiency syndrome (AIDS)-defining
opportunistic infections
Exclusion Criteria:
- Current chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2
inhibitors. We will allow prior use of those agents if patients stop them at least 2
weeks before accrual
- Is currently participating in a study of an investigational anti-cancer agent or
receiving concurrent anti-cancer therapy for metastatic disease
- Has a diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy
- Uncontrolled hypertension is defined as a systolic blood pressure > 150 mmHg or
diastolic blood pressure > 90 mmHg, with or without antihypertensive medications
- Has a history of and/or active cardiac diseases
- History of cardiac diseases including:
- Active myocardial infarction documented by elevated cardiac enzymes or
persistent regional wall abnormalities on assessment of left ventricular
function
- History of documented chronic heart failure; and documented cardiomyopathy
- Active cardiac diseases including:
- Symptomatic angina pectoris within the past 180 days that required the
initiation of or increase in anti-anginal medication or other intervention
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with documented compromise in cardiac function
- Symptomatic pericarditis
- Has preexisting neuropathy > grade 2
- Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical
derivative
- Has medical conditions requiring concomitant administration of strong CYP3A4 or
P-glycoprotein inhibitors or inducers
- Potentially life-threatening second malignancy requiring systemic treatment within the
last 3 years (i.e., patients with a history of prior malignancy are eligible if
treatment was completed at least 3 years before entering the Treatment period and the
patient has no evidence of disease) or which would impede evaluation of treatment
response.
- Hormone ablation therapy is allowed within the last 3 years.
- Patients with history of prior early stage basal/squamous cell skin cancer or
non-invasive or in situ cancers that have undergone definitive treatment at any time
are eligible.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Subjects with previously treated brain metastases may participate if they are stable
and have no evidence of new or enlarging brain metastases. They are not using steroids
for at least 28 days before trial treatment
- Active infection requiring systemic therapy
- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial
- Known active hepatitis B or C
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