Overview

Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer

Status:
Completed
Trial end date:
2019-07-05
Target enrollment:
0
Participant gender:
All
Summary
The purpose of the Phase 1b portion of the study is to determine the best dose of PLX3397 when given in combination with standard dose eribulin (Halaven™). The purpose of the Phase 2 portion of the study is to find out what effects, good and/or bad, these drugs have on patients and their metastatic breast cancer.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hope Rugo, MD
Collaborators:
Plexxikon
Susan G. Komen Breast Cancer Foundation
Criteria
Inclusion Criteria:

- Pathologically confirmed diagnosis of breast cancer with documented progressive
disease.

- Patients with stable brain metastases are eligible for this trial.

- At least one prior chemotherapy regimen for metastatic breast cancer. Prior treatment
must be discontinued at least 2 weeks before treatment start.

- Concomitant therapy with bisphosphonates is allowed.

- Stable dose coumadin anticoagulation is allowed, providing that anticoagulation can be
safely held to an International Normalized Ratio (INR) within normal range for the
purpose of tumor biopsy. Low molecular weight heparin (LMWH is the preferred method of
anticoagulation.

- Prothrombin time (PT)/International Normalized Ratio (INR) and partial thromboplastin
time (PTT) within institutional normal limits within two weeks before initial biopsy.

- Measurable disease, as defined by RECIST guidelines or evaluable disease. Bone
metastases must be evaluable.

- Disease amenable to core biopsy. Patients with pulmonary metastases as their only site
of disease may enroll on this trial and will not undergo biopsy.

- For Phase I: patients with human epidermal growth factor receptor 2 (HER2)
overexpressing disease must have been previously treated with trastuzumab. Patients
with HER2 overexpressing disease are not eligible for the Phase II trial.

- Age eighteen years or older.

- Eastern Cooperative Oncology Group (ECOG) performance status
- Life expectancy of >/= 12 weeks.

- Patients with < grade 1 peripheral neuropathy are eligible for this trial.

- Adequate bone marrow reserve: Absolute Neutrophil Count (ANC) >/= 1000, platelets >/=
100,000.

- Adequate renal function: serum creatinine calculated creatinine clearance ≥ 50 ml/min.

- Sodium, potassium, and chloride levels within institutional normal limits.

- Adequate hepatic function: aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) normal. In patients with liver dysfunction due to hepatic metastases, AST and ALT are
permitted to be
- At baseline: Ejection fraction (EF) ≥ 50%, no evidence of QT prolongation, no history
of congenital long QT syndrome, and no use of drugs known to increase the risk of
Torsades de Point - patients may be eligible for study if the drug can be changed to
another agent with less risk (such as changing from citalopram to an alternate
antidepressant).

- Able to take oral medications and maintain hydration.

- Ability to give written informed consent and willingness to comply with the
requirements of the protocol

- Women of child-bearing potential must agree to use an effective method of birth
control during treatment and for six months after receiving their last dose of study
drug

Specific inclusion criteria for Phase II

• Patients enrolling on the phase II portion of this trial must have ER, progesterone
receptors (PR) and HER2 negative disease defined as less than 10% staining for ER and PR,
and HER2 not amplified byFluorescent in situ hybridization (FISH), 0-1% by
Immunohistochemistry (IHC), or 2+ by IHC and no evidence of amplification by FISH.

Exclusion Criteria:

- Treatment with another chemotherapy or hormonal therapy within the past 2 weeks.

- Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 2
weeks.

- Concurrent treatment with radiotherapy.

- Ongoing treatment with any other investigational therapy.

- Prior treatment with eribulin

- Severe, concurrent illness including congestive heart failure, significant cardiac
disease and uncontrolled hypertension, that would likely prevent the patient from
being able to comply with the study protocol.

- Inadequate bone marrow, renal, or hepatic function as defined above, or an active
coagulopathy that precludes tissue biopsy.

- Pregnant or lactating women and women of child-bearing potential who are not using an
effective method of birth control. Women of childbearing potential must undergo a
serum pregnancy test within seven days of starting the study drug.