Capecitabine and Pegylated Interferon Alfa-2a in Treating Patients With Recurrent or Progressive Brain Metastases Due to Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pegylated interferon alfa-2a may interfere with the growth of tumor cells. Giving capecitabine together with pegylated interferon alfa-2a may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving capecitabine together with pegylated interferon alfa-2a works in treating patients with recurrent or progressive brain metastases due to breast cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the efficacy of capecitabine and pegylated interferon alfa-2a, in terms of 6-month neurologic progression-free rate, in patients with recurrent or progressive brain metastases secondary to breast cancer. Secondary Determine the toxicity spectrum of this regimen in these patients. Determine the time to neurologic progression and overall survival of patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive oral capecitabine twice daily on days 1-14 and pegylated interferon alfa-2a subcutaneously on days 1, 8, and 15. Treatment repeats every 3 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 38-98 patients will be accrued for this study within 2 years.

Official Title
-----------------
Phase II Trial of Capecitabine (Xeloda®) and Pegylated Interferon Alfa-2A(Pegasys®) for Recurrent or Progressive Brain Metastasis From Breast Carcinoma

Conditions
-----------------
Breast Cancer, Metastatic Cancer

Intervention / Treatment
-----------------
* Biological: PEG-interferon alfa-2a
* Drug: Capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed breast cancer that metastasized to the brain, meeting all of the following criteria: Must have ≥ 1 inoperable brain metastases, meeting 1 of the following criteria: Progressive or recurrent disease after prior whole-brain or stereotactic radiotherapy Ineligible for OR unwilling to be treated with radiotherapy At least 1 unidimensionally measurable brain metastasis by enhanced MRI within the past 21 days No progression or development of central nervous system (CNS) metastasis during prior treatment with capecitabine, fluorouracil, interferon alfa, or interferon beta Systemic (i.e., outside the CNS system) cancer must be stable No progressive disease (e.g., liver, lymphangitic, or lung metastases) Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Male or female Menopausal status Not specified Performance status Karnofsky 70-100% Life expectancy More than 12 weeks Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 mg/dL No history of idiopathic thrombocytopenic purpura No known uncontrolled coagulopathy No increased risk for anemia (e.g., thalassemia or spherocytosis) No medically problematic anemia Hepatic aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for patients with concurrent liver metastases ) Bilirubin ≤ 1.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN for patients with concurrent liver metastases; 10 times ULN for patients with concurrent bone metastases) Renal Creatinine ≤ 1.5 times ULN OR Creatinine clearance ≥ 30 mL/min Cardiovascular No congestive heart failure No symptomatic coronary artery disease No medically uncontrolled arrhythmia No other clinically significant cardiac disease No myocardial infarction within the past 12 months Gastrointestinal No history of inflammatory bowel disease Must have intact upper gastrointestinal tract Able to swallow tablets No malabsorption syndrome No history of gastrointestinal bleeding Immunologic No prior unanticipated severe reaction to fluoropyrimidine therapy, interferon, pegylated interferon, or a pegylated moiety No known sensitivity to fluorouracil No serious uncontrolled infection No history of immunologically mediated disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study treatment No known dihydropyrimidine dehydrogenase deficiency No history of depression characterized by a suicide attempt No history of hospitalization for psychiatric disease No history of other severe psychiatric disease No prior disability as a result of psychiatric disease No history of clinically significant psychiatric disability that would preclude study compliance No other malignancy within the past 5 years except cured nonmelanoma skin cancer or treated carcinoma in situ of the cervix No uncontrolled thyroid dysfunction (e.g., thyroid-stimulating hormone not in normal range) No evidence of severe retinopathy (e.g., Cytomegalovirus (CMV) retinitis or macular degeneration) No clinically relevant ophthalmologic disorders due to diabetes or hypertension No other serious uncontrolled medical conditions that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics At least 3 months since prior interferon alfa or interferon beta Chemotherapy See Disease Characteristics At least 3 months since prior capecitabine or fluorouracil Endocrine therapy Concurrent hormonal agents (e.g., tamoxifen, raloxifene, or anastrazole) for breast cancer allowed Radiotherapy See Disease Characteristics Surgery More than 4 weeks since prior major surgery and recovered Other More than 4 weeks since prior participation in another investigational drug study At least 4 weeks since prior and no concurrent brivudine or sorivudine No concurrent cimetidine No other concurrent investigational or commercial agents or therapies for this malignancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine + PEG-interferon alfa-2a<br>Capecitabine 1000 mg/m2 orally twice daily during the first 14 days of each 3-week cycle (2 weeks on, 1 week rest), and PEG-interferon alfa-2a subcutaneously beginning at 180 mcg per week for 21 days. | Biological: PEG-interferon alfa-2a<br>* Once a week subcutaneous injection for 21 days, beginning at 180 mcg per week. Repeated for additional 21 days to begin at the same time as repeat 21 day Capecitabine cycle.<br>* Other names: Pegylated interferon alfa-2a;Drug: Capecitabine<br>* 1000 mg/m^2 twice daily during first 14 days of each 3-week cycle (2 weeks on, 1 week rest).<br>* Other names: Xeloda;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurologic progression-free survival rate at 6 months |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to neurologic progression |  | 6 months or until disease progression | 
| Overall survival |  | Up to 2 years | 
| Tumor response (complete response and partial response) | Response Evaluation Criteria in Solid Tumors (RECIST) criteria for Target (Brain Metastasis) Lesions where Complete Response (CR): Disappearance of all target lesions; and Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | 6 months | 
| Toxicity | Toxicity defined as grade 3 or 4 hematologic, skin (hand and foot syndrome), or fatigue/myalgia/flu debilitation-syndrome (interferon-related) toxicities. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV breast cancer, recurrent breast cancer, male breast cancer, tumors metastatic to brain