View Clinical Trial (Medical Research Study)
GCC 0901- A Phase II Study of Letrozole in Combination With Lapatinib Followed by an Addition of Everolimus in Postmenopausal Women With Advanced Endocrine Resistant Breast Cancer
| City: |
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Baltimore |
| State: |
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Maryland |
| Zip Code: |
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21201 |
| Conditions: |
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Breast Neoplasms - Endocrine Breast Diseases - Neoplasm Metastasis |
| Purpose: |
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About a third of patients with breast cancer are usually treated by hormone pills called
tamoxifen and aromatase inhibitors. Aromatase inhibitors are drugs that stop female hormone
production. Female hormone or estrogen is an important hormone for the growth of breast
cancer cells. Letrozole is one of the aromatase inhibitors that is approved by the FDA and
has been used to treat breast cancer since 1997. However, hormone pills usually work for
about 6-10 months in most patients. Later on, breast cancer will start to grow again. This
condition when hormone pills or endocrine therapy no longer work is called "endocrine
resistant" breast cancer. The scientists here at University of Maryland have discovered how
these cancer cells can become resistant to hormone pills. In our laboratory tests, the
investigators found that lapatinib and everolimus can reverse this resistance and make
letrozole work again. However, it is not known if the drugs can reverse the resistance in
humans.
The purpose of this study is to find out whether the combination of letrozole, lapatinib,
and everolimus is effective in women with breast cancer when hormone pills no longer work.
Lapatinib is an anti-cancer drug that is already approved by the Food and Drug
Administration (FDA). It is the standard of care for the treatment of a particular type of
breast cancer called human epithelial growth factor receptor 2 (HER2)-positive breast
cancer. HER2 is a protein involved in the growth of some cancer cells. This study will also
include patients with HER2-negative breast cancer. This means that the cancer cells in these
patients do not depend on the HER2 protein. The use of lapatinib in these patients is
considered experimental.
Everolimus is also an anti-cancer drug that is approved by the FDA for kidney cancer.
Initial studies in mice and later studies in women with breast cancer have shown that
everolimus may also slow the growth of breast cancer. The use of everolimus is experimental
in this study.
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| Study Summary: |
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This is a single-institution clinical trial. Patients will be stratified according to the
HER2 status:
Group 1: HER2-positive in the tumor tissue Group 2: HER2 negative in the tumor tissue
In the first part of the study, all of the patients will receive the combination of
lapatinib 1,500 mg/day and letrozole 2.5 mg/day. We do not expect any significant toxicity
from this combination since the previous study of lapatinib and letrozole showed that this
combination is safe with no grade 3-4 toxicities observed. Restaging scans (CT scan, MRI,
or bone scan) will be obtained after every 12 weeks of treatment. In those patients who
progress from any group, everolimus 5 mg/day will be added to letrozole and lapatinib will
be reduced to 1,250 mg/day as per the SWOG phase I study of lapatinib and everolimus. The
outcome of each group will continue to be assessed separately. We do not expect to see
additional serious toxicity from adding everolimus to the combination of lapatinib and
letrozole. All of the treatment will be continued until disease progression.
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| Criteria: |
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Inclusion Criteria:
- Female greater than or equal to 18 years.
- Histologically confirmed breast adenocarcinoma with incurable progressing
local-regional or metastatic.
- ER and/or PR positivity of primary and/or secondary tumor.
- Patients must have measurable or evaluable disease.
- Evidence of disease progression or relapse while on or less than 6 months off
aromatase inhibitors or tamoxifen either in adjuvant or first line metastatic
setting.
- Postmenopausal
- Patients may have received up to one prior chemotherapy regimen for stage IV breast
cancer. Prior chemotherapy in the adjuvant and/or neoadjuvant setting is permitted.
Chemotherapy must be finished at least 2 weeks prior to enrollment.
- ECOG performance status <2
- Fasting cholesterol ≤300 mg/dL OR ≤7.75 mmol/LAND fasting triglycerides ≤ 2.5 x ULN
despite appropriate treatment.
- Patients must have adequate organ function as defined by the protocol.
- Stratification 1:
- HER2 positive in the primary or secondary tumor tissue
- Prior trastuzumab therapy is allowed but NOT required. However, trastuzumab
should be discontinued at least 3 weeks prior to enrollment.
- Stratification 2:
- HER2 negative in the primary or secondary tumor tissue
Exclusion Criteria:
- Patients receiving any other investigational agents.
- Prior exposure to lapatinib, everolimus, or other mTOR inhibitors.
- History of allergic reactions or hypersensitivity to compounds similar to everolimus,
lapatinib, or letrozole.
- Patients who have any severe and/or uncontrolled medical conditions that could affect
their participation such as:
- Left ventricular ejection fraction (LVEF) < 50%
- Unstable angina, symptomatic congestive heart failure, myocardial infarction
within 6 months, serious uncontrolled cardiac arrhythmia or any other clinically
significant cardiac disease.
- Severely impaired lung function as defined as spirometry and DLCO that is 50% of
the normal predicted value and/or O2 saturation that is ≤ 88% at rest on room
air.
- Uncontrolled diabetes
- Active or uncontrolled severe infection
- Patients with QTc interval > 0.47 seconds.
- Significant chronic or acute gastrointestinal disorder with diarrhea as a major
symptom.
- Prior exposure to more than 360 mg/m2 doxorubicin, more than 120 mg/m2mitoxantrone,
or more than 90 mg/m2idarubicin, or elevated baseline cardiac troponin I.
- Patients with active CNS metastasis and/or carcinomatous meningtitis. However,
patients with CNS metastasis who have completed a therapy and are clinically stable
for 3 weeks as defined as: (1) no evidence of new or enlarging CNS metastasis and (2)
off steroids and/or anticonvulsants.
- Patient is known to be HIV, Hepatitis B, or Hepatitis C-positive (these tests are not
required).
- Patients with current active hepatic or biliary disease (with exception of patients
with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic
liver disease).
- Patients with INR ≥ 2 or PTT ≥ 2 x upper normal limit.
- Previous or current systemic malignancy other than breast cancer within the past 3
years other than carcinoma in situ of the cervix or basal/squamous carcinoma of the
skin.
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| NCT ID: |
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NCT01499160 |
| Primary Contact: |
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Principal Investigator
Saranya Chumsri, MD
University of Maryland Marlene & Stewart Greenebaum Cancer Center
Nancy Tait, BSN
Phone: 410-328-3546
Email: ntait@umm.edu
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| Backup Contact: |
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Email: jlewis@umm.edu
Jane Lewis, RN
Phone: 410-328-7856
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| Location Contact: |
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Baltimore, Maryland 21201
United States
Nancy Tait, BSN
Phone: 410-328-3546
Email: ntait@umm.edu
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 24, 2013 |
| Modifications to this listing: |
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