A Study of Lapatinib in Combination With Everolimus in Patients With Advanced, Triple Negative Breast Cancer

Study Overview
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Brief Summary
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The patient is being asked to join this clinical research study to find out if lapatinib, an agent that targets a protein, called epidermal growth factor receptor (EGFR) on the surface of cancer cells in combination with everolimus, an agent that targets a protein in the cancer cell, called mammalian target of rapamycin (mTOR) is effective in metastatic triple negative breast cancers that are no longer controlled by standard chemotherapy.

Official Title
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Phase II Trial of Lapatinib in Combination With Everolimus in Triple Negative Metastatic or Locally Advanced Breast Cancer

Conditions
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Breast Neoplasms, Breast Cancer, Cancer of the Breast

Intervention / Treatment
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* Drug: Lapatinib and Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed ER(-), PR(-), HER2(-) locally advanced or metastatic breast cancer Disease progression following prior first line cytotoxic chemotherapy in metastatic setting At least 1 lesion measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Age >18 years old Female Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Left ventricular ejection fraction (LVEF) > 50% Absolute neutrophil count (ANC)>1500/mm3; platelets >100,000/mm3; hemoglobin > 9 g/dL; serum creatinine < 1.5x upper limit of normal (ULN); total bilirubin < 1.5x ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5x ULN Patients must be recovered from both acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial. Patients of childbearing potential agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method) Exclusion Criteria: Patients with current active hepatic or biliary disease (except for patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) Patients with an active infection or with a fever > 101.3 Fahrenheit within 3 days of the first scheduled day of protocol treatment Patients with active central nervous system (CNS) metastases. Patients with stable CNS disease, who have undergone radiotherapy at least 4 weeks prior to the planned first protocol treatment and who have been on a stable dose of corticosteroids for 3 weeks are eligible for the trial History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin or cervical intra-epithelial neoplasia with two consecutive normal pap smears 6 months apart Patients who received radiotherapy to more than 25% of their bone marrow; or patients who received radiotherapy to target lesions within 4 weeks of entry Patients who are receiving concurrent investigational therapy Peripheral neuropathy >= Grade 2 Patients who are pregnant or lactating Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results. History of allogeneic transplant Known HIV or Hepatitis B or C (active, previously treated or both)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Lapatinib plus Everolimus<br> | Drug: Lapatinib and Everolimus<br>* Lapatinib: 1250 mg by mouth daily Everolimus: 5mg by mouth daily<br>* Other names: Affinitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate Will Measured Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Tumor Assessment for All Lesions Must be Performed Every Eight Weeks While on Study by CT Scan. |  | Tumor assessment for all lesions must be performed by CT scan every 8 weeks while on study. | 
| The Safety and Toxicity of the Combination Therapy of Lapatinib and Everolimus Will be Monitored Using the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v. 3.0. The Incidence of Any Grade 3 or 4 Toxicities Will be Analyzed. |  | Safety assessments will be performed every four weeks while the patient remains on study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic breast cancer, Triple negative breast cancer, Estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer