A Phase Ib/II Study of Eribulin in Combination With Cyclophosphamide in Patients With Solid Tumor Malignancies

Inclusion Criteria

INCLUSION

1. 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.

2. Patient is male or female and ≥18 years of age on the day of signing informed
consent.

3. Patient must have performance status of 0-2 on the ECOG Performance Scale and life
expectancy > 3 months.

4. Patient must have evaluable disease. Measureable disease is not required

5. Patient must have adequate organ function

6. Female patient of childbearing potential must have a negative serum or urine
pregnancy test 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.

7. Any number of prior lines of chemotherapy in the metastatic setting is allowed.

8. Concomitant use of bisphosphonates is allowed.

9. 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.

10. Patients willing and able to complete the questionnaires.

11. Patients willing and able to comply with the study protocol for the duration of the
study.

12. 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

1. 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.

2. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade
1.

3. 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.

4. Patients with known active 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:

1. no evidence of new or enlarging CNS metastasis

2. off steroids that are used to minimize surrounding brain edema. Patients with
clinically insignificant brain metastases that do not require treatment are
eligible.

5. Patients with known hypersensitivity to the components of study drug or its analogs.

6. Significant cardiovascular impairment:

1. 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

2. QTc prolongation >480 msec (Bazett's Formula) or congenitally long QT syndrome

7. Severe/uncontrolled concurrent illness/infection

8. Patients with other active, current primary malignancies, other than carcinoma in
situ of the cervix or non-melanoma skin cancer

9. Patients with > Grade 1 neuropathy at screening

10. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical
derivative

11. Patient is pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the study.

12. Patients with other significant disease or disorders that, in the Investigator's
opinion, would exclude the patient from the study