A Phase I Pharmacokinetic, Pharmacodynamic, and Clinical Study of the Combination of the Angiogenesis Inhibitor SU5416 and Doxorubicin in Inflammatory Breast Cancer
- 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
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
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the maximum tolerated dose of SU5416 and doxorubicin in patients with stage IIIB or IV inflammatory breast cancer.
Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.
Beth A. Overmoyer, MD, FACP
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
United States: Federal Government
|Ireland Cancer Center at University Hospitals Case Medical Center||Cleveland, Ohio 44106-5065|