Phase I-II Study of Trastuzumab in Combination With RAD001 in Patients With HER-2 Overexpressing, PTEN-deficient Metastatic Breast Cancer Progressing on Trastuzumab-Based Therapy
RAD001 is a new drug that was designed to block proteins that are important in the
development and growth of cancer. It may also stop the growth of new blood vessels that
help tumor growth, resulting in cell death.
Trastuzumab is a monoclonal antibody that binds to the HER-2 molecule on the surface of
cancer cells. It does not bind to cells that do not have the HER-2 molecule. Trastuzumab
slows the growth of cancer cells and also makes them more able to be treated with other
Before you begin to receive the study drug, you will have what are called "screening tests."
These tests will help the doctor decide if you are eligible to take part in this study.
You will have your complete medical history recorded, and a physical exam, including
measurement of vital signs (blood pressure, heart rate, temperature, and breathing rate)
will be performed. Routine blood tests (about 2 teaspoons) will be collected within 1 week
before therapy. Cancer tissue taken at the time of your initial diagnosis or surgery will
be collected. Special stains will be done that will help find ways in which researchers can
predict the response of your cancer to trastuzumab plus RAD001. Women who are able to have
children must have a negative urine pregnancy test. Some participants may need x-rays
and/or positron emission tomography (PET) scans before receiving study drug and again within
3 weeks after the start of therapy.
If you are found to be eligible to take part in this study, you will receive RAD001 tablets
by mouth once a day. Every 3 weeks (21 days) is considered 1 course of the study. The dose
of trastuzumab you receive on this study will not be different from what you were receiving
before this study started.
If you are participating in the Phase I portion of the study, you will have about 4
teaspoons of blood drawn before you start the study on Day 1. Blood samples will be drawn
prior to initiation of treatment and at 0.5, 1, 2, 5, 8, 24 hours. You will also have
around 4 teaspoons of blood drawn on Day 15 (before the start of treatment and at 0.5, 1, 2,
5, 8, and 24 hours).
While on study, you will have weekly blood tests (about 2 teaspoons) for the first 3 weeks.
After 3 weeks, if you tolerate the study drug well, your blood tests (about 2 teaspoons each
time) will be drawn once every 3 weeks, or as often as your physicians feel that they are
necessary. Six (6) weeks after your first cycle of study drug, you will undergo x-rays,
computed tomography (CT) scans, magnetic resonance imaging (MRI), or PET scans to see how
you are responding to the study drug. If the disease shows a response to the study drug or
is stable, then future x-rays, CT scans, MRI or PET scans will be performed every 6 weeks,
or as often as the physician feels it is necessary. After that, the scans will be performed
every 9 weeks, or as often as the physician feels it is necessary. A physical exam,
including vital signs (blood pressure, heart rate, temperature, and breathing rate), will be
done every 3 weeks and any time the physician feels it is necessary.
You will continue to take the study drug as long as you continue to benefit from it. You
may be removed from this study if you do not respond after 2 courses of the study drug,
intolerable side effects occur, or the disease gets worse. Your dose may be lowered if
certain side effects occur.
Once you come off study, a physical exam, measurement of vital signs (blood pressure, heart
rate, temperature, and breathing rate), a blood test (about 2 teaspoons), x-rays, and/or
scans will be done.
This is an investigational study. Trastuzumab is commercially available for use as a single
therapy or in combination with paclitaxel. However, the combination of trastuzumab and
RAD001 is experimental. The FDA has authorized RAD001 for use in research only. Up to 47
patients will take part in this multicenter study. Up to 36 will be enrolled at UT MD
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Optimal Dose of RAD001 in combination with Trastuzumab
Dose evaluated after cycle 1 for each dose level; Dose-limiting toxicity is defined as any grade 3 or 4 toxicity (based on Common Terminology Criteria (CTC) version 3) except fatigue.
3 week cycle
Francisco Esteva, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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