A Phase II Study of Foretinib in Patients With Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) Negative, Recurrent/Metastatic Breast Cancer
- Histologically or cytologically confirmed diagnosis of invasive breast cancer, that
is estrogen receptor (ER) negative, progesterone receptor (PR) negative and human
epidermal growth factor receptor 2 (HER2) negative.
- Formalin fixed paraffin embedded tissue available for central pathology review and
translational studies. Patients entered on the second stage of accrual must have an
accessible tumour lesion for biopsy.
- Advanced or recurrent/ metastatic disease incurable with standard therapies.
- Clinically and/or radiologically documented measurable disease. At least one site of
disease must be unidimensionally measurable.
- ECOG performance of 0, 1 or 2.
- Age ≥ 18 years of age.
- Previous Therapy: Any treatment-related major organ toxicities must be recovered to ≤
- Patients may have received adjuvant chemotherapy and/or one prior line of
chemotherapy in the recurrent/metastatic setting. A minimum of 21 days since the last
dose of chemotherapy must have elapsed prior to registration.
- No prior therapy with a c-Met inhibitor or angiogenesis inhibitor. Other targeted
agents are permissible provided a minimum of 21 days has elapsed since last day of
targeted therapy and registration.
- Prior radiation therapy permitted provided the patient has recovered from acute toxic
effects of the radiation therapy prior to registration, and at least 21 days have
elapsed from the day of the last fraction of radiation to the date of registration.
Exceptions may be made for non-myelosuppressive radiation to peripheral areas.
- Previous surgery permitted provided wound healing has occurred and at least 14 days
have elapsed if surgery was major.
- Granulocytes (AGC) ≥ 1.5 x 109/L; Platelets ≥ 100 x 109/L
- Serum creatinine ≤ 1.2 x UNL; Total bilirubin ≤ 1.2 x UNL; ALT and AST ≤ 2 x UNL
- Women must be post menopausal, surgically sterile or use a reliable form of
contraception while on study and for 90 days after discontinuing therapy. Women of
childbearing potential must have a pregnancy test taken and proven negative within 7
days prior to registration and must not be lactating.
- Patients who require oral anticoagulants (coumadin, warfarin) are eligible
- Patient consent must be obtained according to local Institutional and/or University
Human Experimentation Committee requirements.
- Protocol treatment must begin within 7 working days of patient registration.
- History of other malignancies, except: adequately treated non-melanoma skin cancer,
curatively treated in-situ cancer of the cervix, or other solid tumours curatively
treated with no evidence of disease for ≥ 5 years.
- Resting BP consistently higher than systolic > 150 mmHg and/or diastolic > 100 mmHg
(in the presence or absence of a stable dose of anti-hypertensive medication) or
poorly controlled hypertension, history of labile hypertension or poor compliance
with anti-hypertensive medication.
- Appreciable cavitating or actively bleeding lesions.
- Untreated brain or meningeal metastases. (Patients with neurologically stable and
treated brain metastases who have discontinued corticosteroids at least two weeks
prior to study registration and have no evidence of cavitation or hemorrhage are
- Untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic
cardiac dysfunction. Patients with a significant cardiac history (even if controlled)
or prior anthracycline exposure are required to have an LVEF > 50%.
- GI tract disease resulting in an inability to absorb oral medication.
- Active or uncontrolled infections, or with serious illnesses or medical conditions
which would not permit the patient to be managed according to the protocol.
- Known hypersensitivity to the study drugs or their components.
- Potent CYP3A4 inhibitors/inducers (e.g. ketoconazole, carbamazepine) must be
discontinued at least 7 days prior to Day 1, Cycle 1.
- Treatment, concurrent or within 3 weeks prior to registration, with other
investigational drugs or anti-cancer therapy.
- Proliferative diabetic retinopathy, retinal arteritis or hemorrhage.
- History of pulmonary embolus or a deep vein thrombosis diagnosed and/or treated
within 6 months prior to registration.