Irinotecan and Etoposide in Treating Patients With Recurrent, Locally Advanced, or Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as irinotecan and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving irinotecan together with etoposide works in treating patients with recurrent, locally advanced, or metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary To determine the response rate, as assessed by RECIST criteria, in patients with recurrent locally advanced or metastatic breast cancer treated with irinotecan hydrochloride and etoposide after prior exposure to anthracycline, taxane, and capecitabine therapy. Secondary To determine the median time to progression in these patients. To determine the response duration and survival in these patients. To measure the type and rate of grade 3 or greater toxicity of this treatment regimen in these patients. OUTLINE: Patients receive irinotecan hydrochloride IV on days 1 and 15 and oral etoposide on days 1-14. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. After completion of study therapy, patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

Official Title
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A Phase II Study: Irinotecan and Etoposide as Treatment for Refractory, Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Etoposide
* Drug: Irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of locally advanced or metastatic breast cancer Recurrent, refractory or progressive disease after receiving prior anthracycline, taxane, and capecitabine therapy Prior anthracycline and taxane therapy may have been as neoadjuvant, or adjuvant therapy if disease progression is documented within a year of completing that agent Received prior capecitabine therapy for metastatic or recurrent disease Measurable disease Bone metastases requires other disease present that can be measured No brain metastases, unless documented to be controlled post-completion of local therapy (surgery and/or radiation therapy) for at least 4 weeks No meningeal carcinomatosis No malignant effusion as the only site of disease recurrence Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified Performance status of 0-2 Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 40 mL/min Hemoglobin ≥ 10 g/dL ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin normal or hyperbilirubinemia < grade 1 (unless due to Gilbert syndrome with elevated total but normal levels of conjugated bilirubin) Not pregnant or nursing Fertile patients must use effective contraception No other non-breast malignancy, except nonmelanoma skin cancer No other serious underlying medical condition, that in the opinion of the treating physician, would make study protocol unreasonably hazardous for the patient or would preclude the patient's ability to comply with the study protocol PRIOR CONCURRENT THERAPY: See Disease Characteristic Recovered from all prior chemotherapy or radiotherapy to NCI CTC grade ≤ 1 Unlimited documented prior chemotherapy regimens allowed No prior irinotecan hydrochloride or etoposide No Hypericum perforatum (St. John's wort) 14 days prior to, during, or 7 days after completion of study therapy At least 7 days since prior and no concurrent phenytoin, carbamazepine, phenobarbital, or any other enzyme-inducing anticonvulsant drug (EIACD) No concurrent aprepitant

Ages Eligible for Study
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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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etoposide and Irinotecan hydrochloride<br>Irinotecan 100 mg/m2 IV days 1 and 15. Etoposide 50 mg PO x14 days followed by 2 weeks off. | Drug: Etoposide<br>* 50 mg PO x14 days followed by 2 weeks off, 28 day/Cycle<br>* Other names: Vepesid;Drug: Irinotecan hydrochloride<br>* Irinotecan 100 mg/m2 IV days 1 and 15, 28 day/Cycle<br>* Other names: Irinotecan hydrochloride trihydrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Progression | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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 | Measured time from the start of treatment to the time the patient is first recorded as having disease progression or dies. If no progression or death while being followed via tumor assessment, censored at last date known alive, assesed up to 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Still alive for a certain period of time after they were diagnosed with or started treatment | Measured from the start of protocol therapy until the date of death from any cause or will be censored at the date the patient was last known to be alive, assesed up to 13 months | 

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