Phase I/II Trial of Letrozole and Sorafenib in Post-Menopausal Hormone-Receptor + Breast Cancer

Study Overview
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Brief Summary
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Letrozole is an aromatase inhibitor that is approved in the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. This phase I/II trial is studying the side effects and best dose of sorafenib when given in combination with letrozole and to see how well they work in treating postmenopausal women with metastatic breast cancer.

Official Title
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Phase I/II Trial of Letrozole (Femara) and Sorafenib (Nexavar) in Postmenopausal Women With Hormone-Receptor Positive Locally Advanced or Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Sorafenib
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive breast cancer Stage IIIB, IIIC with T4 lesion or Stage IV disease Breast cancer must be ER-positive and/or PR-positive Age ³ 18 years of age ECOG performance status 0, 1 or 2 Able to swallow and oral medication Adequate end organ function Written informed consent Exclusion Criteria: Prior hormonal therapy for metastatic disease Prior chemotherapy for metastatic disease Prior treatment with sorafenib Brain metastases or leptomeningeal disease Evidence or history of bleeding Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months

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: Sorafenib and Letrozole<br> | Drug: Sorafenib<br>* sorafenib dose will be given at a daily dose to be determined based upon the phase of study that patient is enrolled The phase II dose of sorafenib will be determined from the phase I portion of the study.<br>* Other names: Nexavar;Drug: Letrozole<br>* Patients will take letrozole orally at a daily dose of 2.5 mg/day on Days 1 through 28<br>* Other names: Femara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sorafenib in Combination With Fixed Dose of of 2.5mg of Letrozole Maximum Tolerated Dose (MTD) | The highest dose of the drug that does not cause unacceptable side effects. The maximum tolerated dose be testing increasing doses until the highest dose with acceptable side effects is found. | twenty eight days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines (Version 1.1) to Letrozole and Sorafenib | Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the malignant lymph nodes are used for tumor measurements. Included will be: complete response, partial response or stable disease of letrozole and sorafenib in the treatment of postmenopausal participants with hormone receptor- positive locally advanced or metastatic breast cancer. Clinical Benefit Rate (CBR) = Progressive Free (PF) + Stable Disease (SD) | 6 months | 
| Median Progressive-Free Survival (PFS) | PFS based on the Kaplan-Meier method is defined as the time between randomization and documented disease progression (PD) per RECIST 1,0 criteria or death, or is censored at time of last disease assessment. Per RECIST 1.0f or target lesions, PD is at least a 20% increase in sum LD of target lesions, taken as reference the smallest sum LD recorded at treatment started. Based on the time between the first day of treatment and and the date of disease progression. | Approximately 4.6 years | 
| Overall Survival (OS) Assessed as Mean Months | From the start of treatment to the end of the study (three years) that participants are still alive. Measured by the mean number. | Approximately 4.6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, Postmenopausal Women with Hormone Receptor-Positive Locally Advanced Breast Cancer