SU5416 and Doxorubicin in Treating Patients With Stage IIIB or Stage IV Inflammatory Breast Cancer

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Treatments

Radiation: radiation therapy

Drug: tamoxifen

Drug: semaxanib

Drug: doxorubicin hydrochloride

Procedure: conventional surgery

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00005822

U01CA062502 (U.S. NIH Grant/Contract)

P30CA043703 (U.S. NIH Grant/Contract)

CWRU5199

NCI-T99-0099

CWRU-5199

Details and patient eligibility

About

RATIONALE: SU5416 may stop the growth of breast cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining SU5416 with chemotherapy may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining SU5416 and doxorubicin in treating patients who have stage IIIB or stage IV inflammatory breast cancer.

Full description

OBJECTIVES:

Determine the maximum tolerated dose of SU5416 and doxorubicin in patients with stage IIIB or IV inflammatory breast cancer.
Determine the overall response, response rate, and progression-free survival rate of patients treated with this regimen.
Determine the antiangiogenic effects of this regimen in these patients.
Assess the relationship of plasma levels of these drugs with safety and efficacy in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive doxorubicin IV continuously over 72 hours on days 1-3 of course 1. For all subsequent courses, patients receive doxorubicin as in course 1 and SU5416 IV over 1 hour twice weekly (on days 1 and 4) beginning on week 2 of course 2. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity. After chemotherapy, all patients undergo a modified radical mastectomy and radiotherapy to the chest wall and regional lymph nodes. Patients with estrogen or progesterone receptor positive disease receive oral tamoxifen for 5 years after radiotherapy.

Cohorts of 3-6 patients receive escalating doses of SU5416 and doxorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 3 patients may be treated at that dose level.

Patients are followed every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 6-9 months.

Enrollment

21 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed stage IIIB or IV (supraclavicular lymph node involvement or metastasis) inflammatory breast cancer
- Primary or secondary
No brain metastases or primary brain tumors
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age:

18 and over

Sex:

Male or female

Menopausal status:

Not specified

Performance status:

ECOG 0-2

Life expectancy:

At least 12 weeks

Hematopoietic:

WBC at least 3,500/mm^3
Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin greater than 9.0 g/dL

Hepatic:

Bilirubin normal
AST and ALT less than 2 times upper limit of normal
PT and PTT normal OR
INR less than 1.1

Renal:

Creatinine less than 1.5 mg/dL OR
Creatinine clearance greater than 60 mL/min

Cardiovascular:

LVEF at least 50% by MUGA
No New York Heart Association class III or IV heart disease
No uncompensated coronary artery disease
No myocardial infarction or unstable angina within the past 6 months
No deep venous or arterial thrombosis within the past 3 months

Pulmonary:

No history of pulmonary embolism within the past 3 months

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of diabetes mellitus with severe peripheral vascular disease
No other prior or concurrent malignancies within the past 10 years except inactive nonmelanomatous skin cancer or carcinoma in situ of the cervix
No other uncontrolled illnesses

PRIOR CONCURRENT THERAPY:

Biologic therapy: