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Breast CancerPhase 1/2NCT00317720

Trastuzumab and RAD001 in Patients With Human Epidermal Growth Receptor 2 (HER-2) Overexpressing Breast Cancer

A Phase 1/2 study testing Trastuzumab and RAD001 in people with Breast Cancer and Neoplasm Metastasis, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Primary Objectives: 1. To identify the optimal dose and pharmacokinetics of RAD001 in combination with trastuzumab in a Phase I trial 2. To determine the efficacy of RAD001 plus trastuzumab in HER-2-overexpressing patients with resistance to trastuzumab-based therapy for metastatic breast cancer in a Phase II trial. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Neoplasm Metastasis
What is being tested?
Trastuzumab and RAD001
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
Apr 2006to Feb 2013
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • Performance status 0-2 (by Eastern Cooperative Oncology Group (ECOG) scale).
  • 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 lower.
  • Age 18 years or older.
  • 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).
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  • Patients must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment.
  • 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.
  • Patients may not be receiving any other investigational agents, and must not have received investigational agents within 15 days of enrollment.
  • Left ventricular ejection fraction determined by echocardiogram or multigated acquisition (MUGA) (cardiac scan) must be 50% or higher.

Who cannot join

  • 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
  • Prior treatment with any investigational drug within the preceding 15 days
  • Chronic treatment with systemic steroids or another immunosuppressive agent
  • 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.
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
  • A known history of HIV seropositivity
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  • 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)
  • Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)
  • Patients who have received prior treatment with an mTor inhibitor.
  • History of noncompliance to medical regimens.
  • Patients unwilling to or unable to comply with the protocol.
  • Patients who are receiving any other investigational agents
  • Patients exhibiting confusion, disorientation, or having a history of major psychiatric illness that may impair the understanding of the informed consent.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: 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

Primary Objectives:

  1. To identify the optimal dose and pharmacokinetics of RAD001 in combination with trastuzumab in a Phase I trial
  2. To determine the efficacy of RAD001 plus trastuzumab in HER-2-overexpressing patients with resistance to trastuzumab-based therapy for metastatic breast cancer in a Phase II trial.
  3. Trastuzumab resistance will be defined as the development of progressive disease after trastuzumab-based therapy for metastatic breast cancer. Patients who develop metastases while receiving adjuvant or neoadjuvant trastuzumab will be eligible.
  4. Efficacy would be measured by the rate of objective response plus stable disease lasting 6 months (complete response (CR) + partial response (PR) + stable disease SD).
Read more

Secondary objectives:

  1. To determine the pharmacokinetics of RAD001 in combination with trastuzumab. In the phase II portion of the study, pharmacokinetic studies will be optional.
  2. To determine the nature and degree of toxicity of RAD001 in combination with trastuzumab in this cohort of patients
  3. To determine expression levels of total and phosphorylated mTOR and p70S6K-T389-P as well as relevant downstream signaling components (e.g., S6, 4E-BP1) in pre- and post- treatment tumor samples.
  4. To correlate biomarker expression with response to therapy.
Read the detailed description

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 Anderson.

Being tested
Trastuzumab, RAD001
Keywords
Breast Cancer, Metastatic Breast Cancer, Trastuzumab, RAD001, Herceptin
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrastuzumabDrug

    Also called Herceptin

    Loading dose = 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle.

    If participant on trastuzumab at time of registration, loading dose deferred and received maintenance dose (6 mg/kg every 3 weeks). If the last trastuzumab dose was given 1 week (for participants receiving 2 mg/kg/week), or 3 weeks before registration (for participants receiving 6 mg/kg every 3 weeks), a loading dose (8 mg/kg) was given followed by maintenance dose.

  • RAD001Drug

    Also called Everolimus

    Starting dose 10 mg by mouth daily. Phase I dose finding from two dose levels of daily RAD001 (5 and 10 mg).

Study groups in NCT00317720
Study groupRoleWhat they receive
Trastuzumab + RAD001ExperimentalTrastuzumab loading dose is 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle. Starting RAD001 dose 10 mg by mouth daily.
Receives: Drug: Trastuzumab; Drug: RAD001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Optimal Dose of RAD001 in Combination With Trastuzumab (Phase I)

    In Phase I, two dose levels of RAD001 were studied: 10 mg (dose level 1) and 5 mg (dose level -1) where each dose was evaluated after cycle 1. At MDACC, the Continual Reassessment Method (CRM) for determining Maximum Tolerated Dose (MTD) was applied to the two predefined RAD001 dose levels; and at DFCI/BIDMC, a 3 x 3 study design was utilized.

    Optimal dose defined as the dose most closely associated with a toxicity rate of 0.20, and toxicity defined as any grade 3 or 4 toxicity (based on Common Terminology Criteria (CTC) version 3.0 except fatigue. Participants underwent clinical evaluation every 3 weeks (one cycle) and radiologic evaluations every 6 weeks. After the second cycle, participants underwent a radiologic evaluation using the same imaging technique used at initial evaluation (ie, computed tomography or magnetic resonance imaging).

    Measured: Following two 3 week cycles of therapy

  2. Clinical Benefit Response Rate (CBR)

    Efficacy measured by the clinical benefit response rate (CBR), defined as confirmed Complete Response (CR) plus Partial Response (PR) at any time plus Persistent Stable Disease (pSD). Confirmed CR is defined as disappearance of all target lesions at the time of radiographic evaluation; pSD was defined as SD lasting 24 weeks. Complete Response (CR): disappearance of all target lesions, and Partial Response (PR): at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as a reference the baseline sum LD. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as references the smallest sum LD since the treatment started.

    Measured: 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2006 (estimated)
  2. Study startApr 2006
  3. Primary completionFeb 2013
  4. Study completionFeb 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00317720
Sponsor's protocol ID
2005-0471
Status last verified
Jun 2026
First submitted
21 Apr 2006
Last updated
2 Jul 2026
Data monitoring committee
No

Publications

  • Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, Kindelberger DW, Coviello J, Sahin AA, Nunez R, Hortobagyi GN, Yu D, Esteva FJ. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol. 2011 Aug 10;29(23):3126-32. doi: 10.1200/JCO.2010.32.2321. Epub 2011 Jul 5.

    PubMed 21730275

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trastuzumab and RAD001 in people with Breast Cancer and Neoplasm Metastasis, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Optimal Dose of RAD001 in Combination With Trastuzumab (Phase I) (time frame: Following two 3 week cycles of therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00317720, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.

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Clinical Trial NCT00317720 | AzTrials