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A Phase I Pharmacokinetic, Pharmacodynamic, and Clinical Study of the Combination of the Angiogenesis Inhibitor SU5416 and Doxorubicin in Inflammatory Breast Cancer


Phase 1
18 Years
N/A
Not Enrolling
Both
Breast Cancer

Thank you

Trial Information

A Phase I Pharmacokinetic, Pharmacodynamic, and Clinical Study of the Combination of the Angiogenesis Inhibitor SU5416 and Doxorubicin in Inflammatory Breast Cancer


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.

Inclusion 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:

- No concurrent epoetin alfa or filgrastim (G-CSF)

Chemotherapy:

- No more than 2 prior chemotherapy regimens allowed

- No prior doxorubicin or other anthracycline

Endocrine therapy:

- Not specified

Radiotherapy:

- Prior radiotherapy allowed

Surgery:

- Not specified

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the maximum tolerated dose of SU5416 and doxorubicin in patients with stage IIIB or IV inflammatory breast cancer.

Outcome Time Frame:

Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.

Safety Issue:

Yes

Principal Investigator

Beth A. Overmoyer, MD, FACP

Investigator Role:

Study Chair

Investigator Affiliation:

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CWRU5199

NCT ID:

NCT00005822

Start Date:

April 2000

Completion Date:

October 2003

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • stage IIIB breast cancer
  • inflammatory breast cancer
  • male breast cancer
  • Breast Neoplasms
  • Inflammatory Breast Neoplasms

Name

Location

Ireland Cancer Center at University Hospitals Case Medical CenterCleveland, Ohio  44106-5065