Edotecarin in Treating Women With Locally Advanced or Metastatic Breast Cancer That Has Not Responded to Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as edotecarin use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase II trial is studying how well edotecarin works in treating women with locally advanced or metastatic breast cancer that has not responded to previous chemotherapy.

Detailed Description
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OBJECTIVES: Primary Determine the antitumor activity of edotecarin in women with anthracycline- and taxane-refractory or chemoresistant locally advanced or metastatic breast cancer. Secondary Determine the time to tumor response and duration of response in patients treated with this drug. Determine the overall survival of patients treated with this drug. Determine the clinical benefit of this drug in these patients. Determine the safety and tolerability of this drug in these patients. Determine the pharmacokinetics of this drug in these patients. OUTLINE: This is an open-label, multicenter study. Patients receive edotecarin IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months until disease progression. PROJECTED ACCRUAL: A total of 31-65 patients will be accrued for this study.

Official Title
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A Phase II Study of Intravenous Edotecarin (PHA-782615) in Patients With Anthracycline- and Taxane-Refractory or Chemoresistant Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: edotecarin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed primary adenocarcinoma of the breast Locally advanced or metastatic disease Not amenable to surgery or radiotherapy with curative intent At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR 10 mm by CT scan Not previously irradiated Meets 1 of the following criteria: Previously treated with anthracycline and concurrent or sequential taxane therapy Refractory to the most recent taxane-based chemotherapy, defined as 1 of the following: Progressive disease during therapy or within 4 months of the last dose with or without documented response for advanced disease Progressive disease within 6 months of completing taxane-based chemotherapy as neoadjuvant therapy Resistant to prior chemotherapy, as defined by progressive disease within 6 months of completing prior chemotherapy for advanced disease No known brain metastases or carcinomatous meningitis* NOTE: *Baseline CT scan or MRI of the brain required if there is clinical suspicion of CNS metastases No spinal cord compression Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Not specified Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9.0 g/dL Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT no greater than 2.5 times ULN (5 times ULN if liver involvement secondary to tumor is present) Albumin at least 3.0 g/dL Renal Creatinine no greater than 1.5 mg/dL Cardiovascular LVEF at least 50% or ULN by echocardiogram or MUGA None of the following within the past 6 months: Myocardial infarction Severe or unstable angina Symptomatic congestive heart failure Cerebrovascular accident or transient ischemic attack Deep vein thrombosis or other significant thromboembolic event No ongoing cardiac dysrhythmias grade 2 or greater No atrial fibrillation of any grade Pulmonary No pulmonary embolism within the past 6 months Gastrointestinal No active inflammatory bowel disease No partial or complete bowel obstruction No chronic diarrhea Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known HIV positivity No active infection No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation or confound study results PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent biological response modifiers No concurrent immunotherapy No concurrent sargramostim (GM-CSF) No other concurrent granulocyte colony-stimulating factors Chemotherapy See Disease Characteristics Prior adjuvant chemotherapy allowed No prior topoisomerase I inhibitors No more than 2 prior chemotherapy regimens for advanced disease No prior high-dose chemotherapy that required hematopoietic stem cell rescue No other concurrent chemotherapy Endocrine therapy Prior adjuvant hormonal therapy or hormonal therapy for advanced/metastatic disease allowed provided that therapy is discontinued before study entry No concurrent hormonal therapy Radiotherapy See Disease Characteristics No prior radiotherapy to more than 25% of the bone marrow No concurrent radiotherapy during and for 5 days after study treatment Palliative radiotherapy allowed provided no more than 20% of the bone marrow is involved Surgery No coronary/peripheral artery bypass graft within the past 6 months Other Recovered from prior therapy (except alopecia or neurotoxicity) At least 4 weeks since any other prior therapy More than 4 weeks since prior investigational agents No concurrent enrollment on another clinical trial No other concurrent approved or investigational anticancer treatment

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: edotecarin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 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