Letrozole and Lapatinib Followed by Everolimus in Women With Advanced Breast Cancer
|ClinicalTrials.gov Identifier: NCT01499160|
Recruitment Status : Terminated (low accrual)
First Posted : December 26, 2011
Results First Posted : March 6, 2018
Last Update Posted : October 22, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Breast Neoplasms Endocrine Breast Diseases Neoplasm Metastasis||Drug: letrozole Drug: lapatinib Drug: everolimus||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||sequential treatment assignment, no masking is done|
|Masking:||None (Open Label)|
|Masking Description:||No masking was done|
|Official Title:||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|
|Actual Study Start Date :||May 2012|
|Actual Primary Completion Date :||November 2014|
|Actual Study Completion Date :||December 2016|
Experimental: HER2-positive or negative
Lapatinib 1,500 mg/day + letrozole 2.5 mg/day until progression followed by everolimus 5 mg/day + letrozole 2.5 mg/day + lapatinib 1,250 mg/day.
Drug is are to be taken orally. 2.5 mg once daily
Other Name: Femara
Drug is to be taken orally. 1,500 mg once daily in the first part of the study and then 1,250 mg once daily in the second part of the study (after initial progression)
Other Name: Tykerb
Drug is to be taken orally. 5 mg once daily.
Other Name: Afinitor
- Clinical Benefit Rate of Patients Treated With the Combination of Letrozole and Lapatinib and Then After Progression, Treated With Everolimus, Letrozole and Lapatinib. [ Time Frame: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Clinical benefit rate is defined as complete response+partial response+ stable disease. All participants will be treated with the combination of letrozole and lapatinib. Once the participant progresses on this regimen, the participant will be treated with everolimus, letrozole and lapatinib until they progress.
- PROGRESSION FREE SURVIVAL TUMOR ASSESSMENT [ Time Frame: From date of study entry until 4 weeks after removal from study or until death (whichever occurs first) up to 24 months. ]Patients treated with the combination of Letrozole and Lapatinib will provide tumor biopsy sample
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01499160
|United States, Maryland|
|University of Maryland Marlene & Stewart Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|Principal Investigator:||Katherine Tkaczuk, MD||University of Maryland Marlene & Stewart Greenebaum Cancer Center|