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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

Phase 1/Phase 2
18 Years
Not Enrolling
Breast Cancer, Neoplasm Metastasis

Thank you

Trial Information

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
chemotherapy drugs.

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

Inclusion Criteria:

1. History of biopsy-proven HER-2-overexpressing breast cancer and radiographic evidence
of metastatic disease. The HER-2 status can be determined either by
immunohistochemistry (score, 3+) or by fluorescence in situ hybridization.

2. History of trastuzumab resistance, defined as the development of progressive disease
after trastuzumab-based therapy for metastatic breast cancer. Patient may not have
received more than 2 prior trastuzumab-based regimens and one lapatinib-based regimen
(either as single agent or in combination with chemotherapy)for metastatic breast
cancer. Patients who develop metastatic disease during or after adjuvant or
neoadjuvant trastuzumab are eligible.

3. Performance status 0-2 (by Eastern Cooperative Oncology Group (ECOG)scale).

4. Absolute neutrophil count (ANC) 1500/µl or higher; Platelets 100,000/µl or higher;
Hemoglobin 9.0 gm/dL or higher; Serum creatinine 2.0 mg/dL or lower; Total bilirubin
1.5 mg/dL or lower; Serum glutamic pyruvic transaminase (SGPT) up to 3* upper limit
of normal; Alkaline phosphatase up to 3* upper limit of normal; Calcium 11.0 mg/dL or

5. Age 18 years or older.

6. Patients must not be pregnant. A pregnancy test will be obtained if the patient is a
woman of child-bearing potential, defined as a sexually mature woman who has not
undergone a hysterectomy or who has not been naturally postmenopausal for at least 24
consecutive months (i.e., who has had menses at any time in the preceding 24
consecutive months).

7. Patients must have signed an informed consent document stating that they understand
the investigational nature of the proposed treatment.

8. Patients must have measurable disease using Response Evaluation Criteria in Solid
Tumors (RECIST). Measurable disease is defined as at least one lesion that can be
accurately measured in at least one dimension with longest diameter >/= 20 mm using
conventional techniques or >/= 10 mm with spiral computed tomography (CT) scan.

9. Patients may not be receiving any other investigational agents, and must not have
received investigational agents within 15 days of enrollment.

10. Left ventricular ejection fraction determined by echocardiogram or multigated
acquisition (MUGA) (cardiac scan) must be 50% or higher.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

2. Prior treatment with any investigational drug within the preceding 15 days

3. Chronic treatment with systemic steroids or another immunosuppressive agent

4. Uncontrolled brain or leptomeningeal metastases, including patients who continue to
require glucocorticoids for brain or leptomeningeal metastases, and patients
diagnosed with brain mets or leptomeningeal disease (LMD) within 3 months.

5. Other malignancies within the past 3 years except for adequately treated carcinoma of
the cervix or basal or squamous cell carcinomas of the skin.

6. A known history of HIV seropositivity

7. Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

8. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication
(except low dose coumadin)

9. Patients who have received prior treatment with an mTor inhibitor.

10. History of noncompliance to medical regimens.

11. Patients unwilling to or unable to comply with the protocol.

12. Patients who are receiving any other investigational agents

13. Patients exhibiting confusion, disorientation, or having a history of major
psychiatric illness that may impair the understanding of the informed consent.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Optimal Dose of RAD001 in combination with Trastuzumab

Outcome Description:

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.

Outcome Time Frame:

3 week cycle

Safety Issue:


Principal Investigator

Francisco Esteva, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

April 2006

Completion Date:

February 2013

Related Keywords:

  • Breast Cancer
  • Neoplasm Metastasis
  • Breast Cancer
  • Metastatic Breast Cancer
  • Trastuzumab
  • RAD001
  • Herceptin
  • Breast Neoplasms
  • Neoplasms
  • Neoplasm Metastasis



UT MD Anderson Cancer Center Houston, Texas  77030