A Phase I Study of the HER1, HER2 Dual Kinase Inhibitor, Lapatinib Plus the Proteosomal Inhibitor Bortezomib in Patients With Advanced Malignancies
- Histologically proven malignant solid tumor with measurable disease
- Progression on, or intolerance of, or ineligibility for all standard therapies
- Biopsy accessible tumor deposits
- LVEF >/= institutional normal
- Corrected QT interval less than 500 milliseconds by EKG
- ECOG performance status 0-2
- Subjects with no brain metastases or a history of previously treated brain metastases
who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior
to enrollment and have a baseline MRI that shows no evidence of active intercranial
disease and have not had treatment with steroids within 1 week of enrollment.
- Adequate hepatic, bone marrow, and renal function
- Partial thromboplastin time must be = 1.5 x upper limit of institution's normal
range and INR < 1.5. Subjects on anticoagulants will be permitted to enroll as long
as the INR is in the acceptable therapeutic range.
- Life expectancy > 12 weeks
- Women of childbearing potential must have a negative serum pregnancy test within 14
days prior to initiation of treatment and/or postmenopausal women must be amenorrheic
for at least 12 months.
- Subject is capable of understanding and complying with parameters as outlines in the
protocol and able to sign and date the informed consent form.
- Patients with lymphomas
- CNS metastases which do not meet the criteria outlines in the inclusion criteria
- Peripheral neuropathy >/= Grade 2 at baseline or peripheral neuropathy >/= Grade 1
with neuropathic pain
- Active severe infection or known chronic infection with HIV or hepatitis B virus
- Cardiovascular disease problems including unstable angina, therapy for
life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or
congestive heart failure within the last 6 months
- Life-threatening visceral disease or other severe concurrent disease
- Women who are pregnant or breastfeeding
- Anticipated patient survival under 3 months
- Concurrent use of known CYP 3A4 inhibiting or activating medications