Everolimus in Treating Patients WIth Recurrent or Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor. PURPOSE: This randomized phase II trial is studying two different schedules of everolimus to see how well they work in treating patients with recurrent or metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of 2 different treatment schedules of everolimus, in terms of clinical/radiological response and early progression, in patients with recurrent or metastatic breast cancer. Secondary Determine the time to progression and response duration in patients treated with these regimens. Determine the toxic effects of these regimens in these patients. Correlate molecular markers of mTOR activity in tumor tissue with objective tumor response in patients treated with these regimens. OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to presence of visceral metastases (yes vs no) and prior chemotherapy regimens for recurrent disease (0 vs 1). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral everolimus once daily on days 1-28. Arm II: Patients receive oral everolimus on days 1, 8, 15, and 22. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 4 weeks and then periodically until disease progression. PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.

Official Title
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A Randomized Phase II Study of Two Different Schedules of RAD001C in Patients With Recurrent/Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: everolimus


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Metastatic or recurrent disease Considered incurable Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Two primary breast cancers allowed Paraffin-embedded primary or metastatic tumor sample available No known brain metastases Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Sex Male or female Menopausal status Not specified Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times ULN Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active uncontrolled infection No upper gastrointestinal condition or other condition that would preclude ability to take oral medication No other serious medical condition that would preclude study participation No psychiatric illness or neurologic disorder that would preclude study compliance No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder PRIOR CONCURRENT THERAPY: Chemotherapy At least 4 weeks since prior chemotherapy Prior adjuvant chemotherapy allowed No more than 1 prior chemotherapy regimen for metastatic or recurrent disease Endocrine therapy At least 5 days since prior hormonal therapy Radiotherapy At least 4 weeks since prior radiotherapy except for low-dose, limited-fraction, palliative, nonmyelosuppressive radiotherapy, defined as radiotherapy to < 20% of functioning bone marrow If prior radiotherapy was to sole site of disease, must have subsequent documented disease progression at that site Surgery At least 3 weeks since prior major surgery Other Concurrent prophylactic bisphosphonates allowed, if started prior to study entry No concurrent potent inhibitors of cytochrome 3A4, such as erythromycin, diltiazem, or ketoconazole and similar antifungals No other concurrent anticancer therapy No other concurrent investigational agents No concurrent grapefruit juice

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Everolimus - 28 days q 4 wk | Drug: everolimus<br> <br> |
| Active Comparator: Arm B<br>Everolimus - days 1, 8, 15 and 22 q 4wks | Drug: everolimus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate by clinical evaluation every 4 weeks and radiologic reevaluation every 8 weeks |  |  | 
| Early progression rate by clinical evaluation every 4 weeks and radiologic reevaluation every 8 weeks |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event rates |  |  | 
| Time to progression by clinical evaluation every 4 weeks and radiologic reevaluation every 8 weeks |  |  | 
| Response duration by evaluation 4 weeks after response and then every 8 weeks |  |  | 
| Correlative assessment of response with molecular markers of mTor activity on archival tissue |  |  | 
| Optional correlative assessment of response with molecular markers of mTor activity on fresh tissue |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer, male breast cancer