Breast CancerPhase 2NCT00912340
Phase II Trial of EVEROLIMUS ± Trastuzumab in Hormone-Refractory Metastatic Breast Cancer
A Phase 2 study testing Everolimus and Trastuzumab in people with Breast Cancer, run by Emory University at 4 sites in United States.
Trial summary
This phase II trial studies how well everolimus with or without trastuzumab works in treating patients with breast cancer that has not responded to hormone therapy and has spread from where it started to other places in the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Everolimus and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2009to Jul 2017
- Phase
- Phase 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
- Patients will be included in the study based on the following criteria:
- Hormone-refractory metastatic breast cancer defined as disease progression within 6 months from starting most recent hormonal therapy
- At least one line of endocrine therapy in the metastatic setting
- Candidate for hormonal therapy (ER and/or progestin receptor [PR]-positive at primary diagnosis and at metastatic diagnosis where tissue is available)
- HER2/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH]-negative if IHC 3+) at primary diagnosis
- Must have a biopsy in the metastatic setting with HER2 expression of 1+ or 2+ by IHC
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- If biopsy of metastatic lesion is performed prior to study entry, HER2 expression by IHC must be 1+ or 2+
- Histologically confirmed, measurable or evaluable disease; if disease is measurable, Response Evaluation Criteria In Solid Tumors (RECIST) criteria should be used
- Life expectancy > 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Adequate bone marrow function as indicated by the following:
- Absolute neutrophil count (ANC) > 1500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin > 10 g/dL
- Adequate renal function, as indicated by creatinine ≤ 1.5x upper limit of normal (ULN)
- Adequate liver function, as indicated by bilirubin ≤ 1.5x ULN
- International normalized ratio (INR) ≤ 1.3 (or ≤ 3 on anticoagulants)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x ULN unless related to primary disease
- Signed informed consent
- Adequate birth control
- Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
Who cannot join
- Patients will be excluded from the study based on the following criteria:
- Prior treatment with trastuzumab or other HER2-directed therapies or with an mammalian target of rapamycin (mTOR) inhibitor within 12 months of study entry (when cancer was not definitely hormone refractory)
- HER2 0 or 3+ by IHC on pre-treatment biopsy of metastatic lesion (if performed)
- Active infection
- Uncontrolled central nervous system metastases
- Life-threatening, visceral metastases
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- Pregnant or lactating women
- Prior chemotherapy within the last 4 weeks
- Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
- Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
- Ejection fraction < 50% or below the lower limit of the institutional normal range, whichever is lower
- Hypersensitivity to trial medications
- Emotional limitations
- Prior treatment with any investigational drug within the preceding 4 weeks
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent
- Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN
- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- A known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus)
- Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
- Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
- Taking any of the following agents:
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Live vaccines
- Drugs or substances known to be inhibitors or inducers of the isoenzyme cytochrome P450, family 3, subfamily A (CYP3A)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
About this study
This phase II trial studies how well everolimus with or without trastuzumab works in treating patients with breast cancer that has not responded to hormone therapy and has spread from where it started to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving everolimus and adding trastuzumab at the time of disease progression may be an effective treatment for breast cancer.
Read the detailed description
Breast cancer is the most common type of invasive cancer in women, with more than 1 million cases and almost 600,000 deaths occurring worldwide annually. Breast cancer that has spread to other parts of the body (metastasized) is usually not curable. Patients with a type of metastatic breast cancer that has hormone receptors on the surface of the cancer cells are usually treated with the drug tamoxifen, which interferes with the function of these hormone receptors. However, the average survival time for these patients remains at around 36 months.
In patients who no longer respond to tamoxifen (hormone-refractory breast cancer), the cancer drug trastuzumab (Herceptin), which acts on a protein called human epidermal growth factor receptor 2 (HER2), may have some activity. In addition, studies suggest that the drug everolimus, which acts on a pathway within cancer cells that is important for growth of the tumor, may make the cancer cells more sensitive to treatment with trastuzumab. Thus, the two drugs may act together to increase their anti-cancer potential.
- Conditions
- Breast Cancer
- Being tested
- Everolimus, Trastuzumab
- Keywords
- Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Afinitor, RAD001
TrastuzumabBiological
Also called Herceptin
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab | Experimental | Patients receive trastuzumab IV over 30 minutes once every 3 weeks and continue to receive their most recent hormone therapy. Patients achieving disease progression receive everolimus PO daily in combination with trastuzumab and hormone therapy. Receives: Biological: Trastuzumab |
| Everolimus | Experimental | Patients receive everolimus PO daily and continue their most recent hormone therapy. Patients achieving disease progression receive trastuzumab IV over 30-90 minutes once every 3 weeks in combination with everolimus and hormone therapy. Receives: Drug: Everolimus |
| Trastuzumab and everolimus (ARM REMOVED) | Experimental | Patients receive trastuzumab IV over 30 minutes once every 3 weeks and everolimus PO daily while continuing to receive their most recent hormone therapy. Receives: Drug: Everolimus; Biological: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) Until First Progression
Median PFS will be calculated based on time to first progression or death.
Measured: Every 3 to 4 weeks after study start, until progression or death, assessed up to 5 years
Secondary outcomes (1)
Progression-free Survival (PFS) in Patients Who Crossed Over
Median PFS will be calculated based on time to first progression or death.
Measured: Every 3 to 4 weeks after study start, until progression or death, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2009 (estimated)
- Study startMay 2009
- Primary completionJul 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Novartis Pharmaceuticals
- Responsible party
- Principal investigator, Elisavet Paplomata, Emory University
- Investigators
- Elisavet Paplomata, MD, Principal investigator, Emory University Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00912340
- Sponsor's protocol ID
- IRB00012495
- Other IDs
- WCI1524-08
- Status last verified
- Nov 2018
- First submitted
- 2 Jun 2009
- Last updated
- 5 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of EVEROLIMUS ± Trastuzumab in Hormone-Refractory Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00912340
- Acronym / sponsor ID
- IRB00012495
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc., Novartis Pharmaceuticals
- Study start
- May 2009
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 3 Jun 2009 (estimated)
- Results
- Posted 5 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well everolimus with or without trastuzumab works in treating patients with breast cancer that has not responded to hormone therapy and has spread from where it started to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving everolimus and adding trastuzumab at the time of disease progression may be an effective treatment for breast cancer.
Detailed description
Breast cancer is the most common type of invasive cancer in women, with more than 1 million cases and almost 600,000 deaths occurring worldwide annually. Breast cancer that has spread to other parts of the body (metastasized) is usually not curable. Patients with a type of metastatic breast cancer that has hormone receptors on the surface of the cancer cells are usually treated with the drug tamoxifen, which interferes with the function of these hormone receptors. However, the average survival time for these patients remains at around 36 months.
In patients who no longer respond to tamoxifen (hormone-refractory breast cancer), the cancer drug trastuzumab (Herceptin), which acts on a protein called human epidermal growth factor receptor 2 (HER2), may have some activity. In addition, studies suggest that the drug everolimus, which acts on a pathway within cancer cells that is important for growth of the tumor, may make the cancer cells more sensitive to treatment with trastuzumab. Thus, the two drugs may act together to increase their anti-cancer potential.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab | Experimental | Biological: TrastuzumabPatients receive trastuzumab IV over 30 minutes once every 3 weeks and continue to receive their most recent hormone therapy. Patients achieving disease progression receive everolimus PO daily in combination with trastuzumab and hormone therapy. |
| Everolimus | Experimental | Drug: EverolimusPatients receive everolimus PO daily and continue their most recent hormone therapy. Patients achieving disease progression receive trastuzumab IV over 30-90 minutes once every 3 weeks in combination with everolimus and hormone therapy. |
| Trastuzumab and everolimus (ARM REMOVED) | Experimental | Drug: Everolimus, Biological: TrastuzumabPatients receive trastuzumab IV over 30 minutes once every 3 weeks and everolimus PO daily while continuing to receive their most recent hormone therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Hormone-refractory metastatic breast cancer defined as disease progression within 6 months from starting most recent hormonal therapy
- At least one line of endocrine therapy in the metastatic setting
- Candidate for hormonal therapy (ER and/or progestin receptor [PR]-positive at primary diagnosis and at metastatic diagnosis where tissue is available)
- HER2/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH]-negative if IHC 3+) at primary diagnosis
- Must have a biopsy in the metastatic setting with HER2 expression of 1+ or 2+ by IHC
Key exclusion criteria (28 listed)
- Prior treatment with trastuzumab or other HER2-directed therapies or with an mammalian target of rapamycin (mTOR) inhibitor within 12 months of study entry (when cancer was not definitely hormone refractory)
- HER2 0 or 3+ by IHC on pre-treatment biopsy of metastatic lesion (if performed)
- Active infection
- Uncontrolled central nervous system metastases
- Life-threatening, visceral metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: Afinitor, RAD001 | Drug | Everolimus, Trastuzumab and everolimus (ARM REMOVED) |
| TrastuzumabAlso: Herceptin | Biological | Trastuzumab, Trastuzumab and everolimus (ARM REMOVED) |
Primary outcome
Progression-free Survival (PFS) Until First Progression
Time frame: Every 3 to 4 weeks after study start, until progression or death, assessed up to 5 years
Median PFS will be calculated based on time to first progression or death.
1 secondary outcome
Progression-free Survival (PFS) in Patients Who Crossed Over
Time frame: Every 3 to 4 weeks after study start, until progression or death, assessed up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elisavet Paplomata, MD principal investigator
Emory University Winship Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and Trastuzumab in people with Breast Cancer, run by Emory University at 4 sites 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 21 inclusion and 28 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 5 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 phase mean?
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 5 Dec 2018). 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?
Progression-free Survival (PFS) Until First Progression (time frame: Every 3 to 4 weeks after study start, until progression or death, assessed up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Dec 2018; AzTrials last refreshed its copy on 8 Nov 2026.