Eribulin in Combination With Cyclophosphamide in Patients With Solid Tumor Malignancies

INCLUSION CRITERIA

• Phase Ib: Patient must have histologically or cytologically documented solid tumor malignancies.

Phase II: Patients must have histologically or cytologically confirmed locally advanced, unresectable or metastatic carcinoma of the breast.

• Patient is male or female and ≥18 years of age on the day of signing informed consent.
• Patient must have performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale and life expectancy > 3 months.
• Patient must have evaluable disease. Measureable disease is not required
• Patient must have adequate organ function
• Female patient of childbearing potential must have a negative serum or urine pregnancy test quantitative human chorionic gonadotropin (β-hCG) within 72 hours prior to receiving the first dose of study medication and agree to the use of effective methods of contraception while on study.
• Any number of prior lines of chemotherapy in the metastatic setting is allowed.
• Concomitant use of bisphosphonates is allowed.
• Patients with stable and clinically insignificant CNS disease are allowed. Patients must be off steroids with no new CNS symptoms or findings on radiographic imaging for 1 month.
• Patients willing and able to complete the questionnaires.
• Patients willing and able to comply with the study protocol for the duration of the study.
• Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.

EXCLUSION CRITERIA

• Patients who have had chemotherapy or radiotherapy within two weeks, 4 weeks for nitrosoureas, mitomycin C, pegylated-doxorubicin and one half-life for bevacizumab, hormone therapy within one week, trastuzumab within 2 weeks or lapatinib within one week of study Day 1.
• If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1.
• Patients with non-healing surgical wounds. Patients must be at least two weeks from a major surgical procedure, and surgical wounds must be completely healed.
• Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as:
• no evidence of new or enlarging CNS metastasis
• off steroids that are used to minimize surrounding brain edema. Patients with clinically insignificant brain metastases that do not require treatment are eligible.
• Patients with known hypersensitivity to the components of study drug or its analogs.
• Significant cardiovascular impairment:
• Congestive heart failure, Clinically significant cardiac arrhythmia, history or current evidence of a myocardial infarction during the last 6 months, and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator, or unstable angina
• QTc prolongation >480 msec (Bazett's Formula) or congenitally long QT syndrome (LQTS)
• Severe/uncontrolled concurrent illness/infection
• Patients with other active, current primary malignancies, other than carcinoma in situ of the cervix or non-melanoma skin cancer
• Patients with > Grade 1 neuropathy at screening
• Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative
• Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
• Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study