Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

This is a Phase I/Phase II open-label single arm trial of dovitinib in combination with
anastrozole 1 mg daily, exemestane 25 mg daily, or letrozole 2.5 mg daily. Study subjects
will receive the aromatase inhibitor on which they had previously derived clinical benefit.

Inclusion Criteria:

- Female patients with breast cancer either in the primary or metastatic setting

- Tumor must be estrogen receptor and/or progesterone receptor positive and Her-2
negative

- Evidence of disease resistance to an aromatase inhibitor

- ECOG performance status 0 or 1

- Age 18 years or older

- Adequate laboratory values

- Able to give written informed consent

- Measurable disease

- No more than 2 prior chemotherapy regimens in the metastatic setting

- Unlimited prior hormonal therapy in the metastatic setting

- Life expectancy of greater than 3 months

- Post-menopausal

- Tumor must be available for central testing for FGFR1 amplification by FISH/CISH

Exclusion Criteria:

- Brain metastases

- Another primary malignancy within 3 years prior to starting drug therapy with the
exception of adequately treated in-site carcinoma of the uterine cervix or skin cancer

- Chemotherapy within 3 weeks prior to starting study drug or not recovered from side
effects of previous therapy

- Administration of nitrosurea or mitomycin-C within 6 weeks prior to starting study
drug or not recovered from side effects of such therapy

- Administration of biologic therapy within 6 weeks prior to starting study drug or not
recovered from side effects of such therapy

- Radiotherapy within 4 weeks prior to starting study drug or 2 weeks in the case of
localized radiotherapy or not recovered from radiotherapy toxicities

- major surgery, open biopsy or significant traumatic injury within 4 weeks prior to
starting study drug or a minor procedure, percutaneous biopsy or placement of a
vascular access device within 1 week prior to starting study drug or not recovered
from side effects of such procedure or injury

- Chronic concomitant bisphosphonate therapy for the prevention of bone metastases.
Bisphosphonate/ denosumab therapy for the management of bone metastases or for the
treatment of osteoporosis s allowed.

- Impaired cardiac function or clinically significant cardiac disease

- Impairment of GI function or GI disease that may significantly alter the absorption of
dovitinib

- Cirrhosis, chronic active hepatitis, or chronic persistent hepatitis

- Known diagnosis of HIV infection

- Anticoagulation treatment with therapeutic doses of warfarin

- Any concurrent severe and/or uncontrolled concomitant medical condition that could
cause unacceptable safety risks or compromise compliance with the protocol

- Pregnant or breast-feeding

- Unwilling or unable to comply with the protocol