A Phase I Trial of KRN5500 (NSC 650426) Given as a 72 Hour Continuous IV Infusion Every 21 Days in Patients With Solid Tumors
I. To establish the MTD and identify the DLTs of the investigational agent KRN5500 when
administered by a 72-hr continuous i.v. infusion to patients with solid tumors who have
failed standard therapy or for whom no standard therapy exists.
II. To establish and assess the safety of an appropriate dose for phase II studies.
III. To characterize the pharmacokinetics of KRN5500 in patients when administered by a 72
hr continuous IV infusion.
IV. To characterize the response to KRN5500 by FLT-PET scanning at the MTD.
I. To describe any preliminary evidence of antitumor activity. II. Establish pharmacodynamic
relationships for the pharmacological effect of the drug upon surrogate markers of activity
and host toxicity.
III. To compare the toxicity profiles for the 1 hr i.v. infusion and 72 hr continuous i.v.
infusion administration schedules.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive KRN5500 IV over 24-72 hours on day 1. Treatment repeats every 21 days in
the absence of disease progression or unacceptable toxicity.
Cohorts of 1-3 patients receive KRN5500 at the starting dose over escalating infusion
durations. After the longest duration of infusion time is safely reached, cohorts of 3-6
patients receive escalating doses of KRN5500 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, additional patients are
accrued to receive treatment with KRN5500 at the recommended phase II dose.
Patients are followed every 4 weeks until resolution of all toxicity.
PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximally tolerated dose (MTD) and dose limiting toxicities (DLTs) of KRN5500, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Up to 21 days
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|