A Phase I Study Of UCN-01 In Combination With Irinotecan In Resistant Solid Tumor Malignancies (Part I) and in Triple Negative (ER-negative, PgR-negative, HER-2 Not Amplified) Recurrent Breast Cancers (Part II)
I. Determine the maximum tolerated dose of UCN-01 (7-hydroxystaurosporine) and irinotecan
(irinotecan hydrochloride) in patients with resistant solid tumors. (Part I [closed to
accrual as of 6/8/2007]) II. Determine the dose-limiting toxicity of this regimen in these
patients. (Part I [closed to accrual as of 6/8/2007]) III. Determine the types of toxic
effects of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) IV.
Determine the anti-tumor activity in terms of overall response rate (partial response [PR]
and complete response [CR]), clinical benefit rate (PR, CR, and stable disease), and time
to disease progression in patients with estrogen receptor-negative, progesterone
receptor-negative, and HER-2 not amplified (triple negative) locally recurrent or metastatic
breast cancer treated with this regimen. (Part II) V. Determine the side effect profile of
this regimen in patients with triple negative recurrent breast cancer. (Part II)
I. Determine any anti-tumor activity of this regimen in these patients. (Part I [closed to
accrual as of 6/8/2007]) II. Determine the pharmacokinetics of this regimen in these
patients. (Part I [closed to accrual as of 6/8/2007]) III. Determine the activity of the
serum α-acid glycoprotein and correlate this level with free UCN-01 concentrations. (Part I
[closed to accrual as of 6/8/2007]) IV. Determine the in vivo mechanisms of UCN-01 activity
in these patients.
OUTLINE: This is a dose-escalation study.
PART I: Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on days
1, 8, 15, and 22 and 7-hydroxystaurosporine IV over 3 hours on days 2 and 23. Courses repeat
every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6
patients receive escalating doses of irinotecan hydrochloride and 7-hydroxystaurosporine
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. Blood
samples are collected periodically during study treatment.
PART II: (treatment of triple negative recurrent breast cancer): Patients receive irinotecan
hydrochloride IV and 7-hydroxystaurosporine IV as in part I at the MTD and undergo blood
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)
Defined as the highest dose given to at least 6 patients in which =< 1 out of 6 experience dose limiting toxicity (DLT).
University of Virginia
United States: Food and Drug Administration
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