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

NCT ID: NCT00074100

Last Updated: 2013-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-08-31
• Study Completion Date: 2004-09-30

Brief Summary

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

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.

Conditions

Breast Cancer

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

amonafide dihydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Clifford A. Hudis, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

MSKCC-03080

Identifier Type: -

Identifier Source: secondary_id

CDR0000341687

Identifier Type: REGISTRY

Identifier Source: secondary_id

XANTHUS-0001A1-200-GL

Identifier Type: -

Identifier Source: org_study_id