Lapatinib and Bortezomib in Patients With Advanced Malignancies

Georgetown University

Status and phase

Terminated

Phase 1

Conditions

Advanced Solid Tumors

Treatments

Drug: Lapatinib and bortezomib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01497626

XO5371 (Other Identifier)

2010-533

8LAP114999 (Other Identifier)

Details and patient eligibility

About

This study is for patients with an advanced type of cancer for which no curative treatment exists.

The purpose of this study is to test the safety and efficacy of the combination of the study drugs, lapatinib and bortezomib. Lapatinib is a drug that targets two proteins important for the growth of cancer cells known as HER1 (EGFR) and HER2. By inhibiting these proteins, lapatinib can inhibit cancer cell growth and even lead to their death. Lapatinib is an oral pill given by mouth once every day. Lapatinib is approved by the FDA for patients with breast cancer.

Bortezomib is a drug that targets a part of cancer cells known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 2 out of every 3 weeks. Bortezomib is approved by the FDA for patients with multiple myeloma and mantle cell lymphoma.

This research is being done because it is not known if the combination of lapatinib and bortezomib will work better than lapatinib or bortezomib alone, although in the lab and in animal studies the combination of the two drugs was much more effective than either drug alone.

As part of this study biopsies will be taken of patients' tumors before any treatment, after starting lapatinib alone, and after receiving both lapatinib and bortezomib. Investigators want to study what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.

Enrollment

15 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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