Amonafide in Treating Women With Metastatic Breast Cancer That Has Progressed After Previous Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as amonafide, work in different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of amonafide in treating women who have metastatic breast cancer that has progressed after previous chemotherapy.

Detailed Description
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OBJECTIVES: Primary Determine the time to progression in women with metastatic breast cancer who have progressed after prior chemotherapy and are now treated with amonafide. Determine the overall response rate (complete and partial response) in patients treated with this drug. Determine the safety of a phenotypically driven dosing regimen of this drug in these patients. Secondary Determine the time to tumor response, duration of response, and time to treatment failure in patients treated with this drug. Determine the overall survival of patients treated with this drug. Determine the pharmacokinetic profile of this drug in these patients. OUTLINE: This is an open-label, multicenter study. Patients receive amonafide IV over 1 hour on days 1-5. Treatment repeats every 21 days for at least 5 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive additional courses (beyond 5 courses) at the investigator's discretion. Patients are followed at 30 days and then every 3 months. PROJECTED ACCRUAL: A total of 175 patients will be accrued for this study within 1 year.

Official Title
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Amonafide: Individual Phenotype-Adjusted Chemotherapy for Women With Metastatic Breast Cancer Who Have Progressed Despite Prior Chemotherapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: amonafide dihydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Metastatic (stage IV) disease Relapsed after 1 of the following prior therapy regimens*: Adjuvant therapy containing an anthracycline and a taxane Adjuvant anthracycline therapy followed by first-line metastatic treatment containing a taxane NOTE: *No relapse within 12 months of initiation of prior therapy Measurable disease by CT scan or MRI No ascites, pleural effusions, or osteoblastic bone metastases as the only site of measurable disease Refractory to hormonal anticancer therapy completed more than 4 weeks before study therapy HER2/neu positive allowed provided patient received prior trastuzumab (Herceptin®) MUGA or echocardiogram normal while on trastuzumab No known history of or current brain or leptomeningeal metastases Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age Over 18 Sex Female Menopausal status Not specified Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic WBC at least 3,000/mm^3 Neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL No clinically significant abnormal hematological parameters Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN in case of liver metastases) AST or ALT no greater than 2.5 times ULN (5 times ULN in case of liver metastases) Renal Creatinine no greater than 1.5 times ULN Cardiovascular See Disease Characteristics No myocardial infarction within the past 3 months No unstable angina pectoris No New York Heart Association class III or IV heart disease No uncontrolled arrhythmia No cardiac insufficiency No uncontrolled hypertension LVEF at least 50% OR at least lower limit of normal Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception 4 weeks before, during, and for at least 4 weeks after study participation No preexisting neuropathy (motor or sensory) greater than grade 2 No clinically significant abnormal biochemical parameters No clinically significant active infection No other prior malignancy except cured nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix No other serious illness or medical condition No psychological illness or condition that would preclude study participation No other known condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics More than 3 months since prior trastuzumab More than 2 weeks since prior growth factor therapy (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF]) No concurrent systemic anticancer immune modulators Chemotherapy See Disease Characteristics Endocrine therapy See Disease Characteristics More than 4 weeks since prior hormonal therapy No concurrent anticancer hormonal therapy No concurrent chronic systemic steroids Concurrent topical or inhaled steroids for dermatological or allergy/asthma conditions allowed provided therapy was initiated prior to study enrollment Concurrent hormone replacement therapy allowed provided therapy was initiated prior to study enrollment Radiotherapy More than 30 days since prior radiotherapy No concurrent radiotherapy directed at target lesions Surgery At least 4 weeks since prior major surgery and recovered Other More than 30 days since prior investigational new drug More than 2 weeks since prior blood transfusion No other concurrent systemic anticancer agents, including immunosuppressive agents No other concurrent investigational agents Concurrent bisphosphonates allowed provided therapy was initiated prior to study enrollment

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: amonafide dihydrochloride|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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stage IV breast cancer, recurrent breast cancer