A Phase I, Dose Escalation and Pharmacokinetics Study of Temperature Sensitive Liposome Encapsulated Doxorubicin (ThermoDox™) and Hyperthermia in Patients With Local-Regionally Recurrent Breast Cancer
- Determine the maximum tolerated dose of temperature-sensitive liposomal doxorubicin
(ThermoDox™) when used in combination with local-regional hyperthermia in women with
locally recurrent breast cancer.
- Determine the pharmacokinetic profile of ThermoDox™ when used in multiple-course
OUTLINE: This is a dose-escalation study of temperature-sensitive liposomal doxorubicin
Patients receive ThermoDox™ IV over 30 minutes immediately followed by hyperthermia to the
chest wall/axilla over 1-2 hours on day 1. Treatment repeats every 21-35 days for up to 6
courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ThermoDox™ (with or without
standard-dose granulocyte colony-stimulating factor [G-CSF] support) until the maximum
tolerated dose (MTD) is determined. The MTD without G-CSF support is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).
At least 6 patients are treated at the MTD. If the only DLT is neutropenia in > 1 of 6
patients treated at any dose level, then additional cohorts of 3-6 patients receive
escalating doses of ThermoDox™ with G-CSF support (standard-dose G-CSF or standard-dose
pegfilgrastim) until the MTD is determined. The MTD with G-CSF support is defined as the
dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT after the addition of
Quality of life and pain are assessed at baseline, prior to courses 3 and 5, and at 21-42
days after completion of therapy.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of temperature-sensitive liposomal doxorubicin (ThermoDox™) in combination with hyperthermia
Kimberly L. Blackwell, MD
Duke Cancer Institute
United States: Food and Drug Administration
|Duke Cancer Institute||Durham, North Carolina 27710|