Phase I Study of T-DM1 Alone Versus T-DM1 and Metronomic Temozolomide in Secondary Prevention of HER2-Positive Breast Cancer Brain Metastases Following Stereotactic Radiosurgery

Alexandra Zimmer, M.D., at the National Cancer Institute, Bethesda, MD

The purpose of this study is to investigate whether using Temodar and Kadcyla together decreases the chance of patients with HER2+ metastatic breast cancer developing new brain metastases. Approximately 18 participants will take part in this study. Participants enrolled in this trial may be eligible to receive compensation for their travel expenses.

What does participation involve?

Screening Visit

If you sign up for this study, you will be contacted by the research team and asked to visit the Clinical Center at the NIH for a screening visit. Before your visit, you may submit recent tests (laboratory and imaging) for review by the research team as an initial eligibility check. During the screening visit, you will have several exams and tests to ensure you are a good fit for the study, including a review of your medical history, physical examination, electrocardiogram (EKG), echocardiogram, CT scan, MRI, bloodwork, and a pregnancy test. Additionally, you will be asked to provide a copy of your tumor pathology report to confirm your diagnosis. Participants who enroll in this study will continue treatment until their disease gets worse.

Treatment Phase

The purpose of this phase I clinical trial is to evaluate the safety of using Temodar with Kadcyla.  Volunteers will receive increasing doses of Temodar to determine the best dose to use in combination with Kadcyla.

All participants in this part of the study will receive both study medications. You will receive Kadcyla once every three weeks through an IV. You will take Temodar, an oral drug, every day. The research team will monitor your side effects and conduct tests to determine how you are responding to the two drug combination. Every three weeks you will have a physical exam, testing of your vital signs, blood tests, urine tests, symptom review, and a pregnancy test. Every six weeks, you will complete questionnaires and receive an MRI and/or CT scan. An EKG and echocardiogram will be performed every 12 weeks.

To lean more about the effects the two-drug combination is having on your tumor, the research team will study your blood samples, a tumor sample, and your cerebrospinal fluid. Tumor samples will be requested from surgeries you had before or during the study. You will not have any biopsies performed just for research purposes. Cerebrospinal fluid will be collected by the research team. These samples are obtained by a procedure called a lumbar puncture. You are required to have two lumbar punctures: once before treatment and once at the beginning of cycle 3. 

Throughout the study, you will complete a daily medication diary. This diary will help the research team record your medication use.

National Institutes of Health Clinical Center, Bethesda, MD