A Phase I Study of NX 211 in Combination With Cisplatin Given as an IV Infusion Days 1, 2, and 3 Every 3 Weeks in Patients With Solid Tumors
OBJECTIVES: I. Determine the maximum tolerated dose and recommended phase II dose of
lurtotecan liposome and cisplatin in patients with advanced solid tumors. II. Determine the
toxicity profile, dose-limiting toxic effects, and the pharmacokinetics of this treatment
regimen in this patient population. III. Determine any correlation between toxicity profile
and pharmacokinetics of this treatment regimen in these patients. IV. Determine the
objective tumor response to this treatment regimen in patients with measurable disease
(previously untreated solid tumors) entered at the recommended phase II dose.
OUTLINE: This is an open-label, multicenter, dose-escalation study of lurtotecan liposome.
Patients receive cisplatin IV over 1 hour followed by lurtotecan liposome IV over 30 minutes
on days 1-3. Treatment repeats every 3 weeks in the absence of disease progression or
unacceptable toxicity. Once the total dose of cisplatin is reached, patients receive
lurtotecan liposome alone. Patients achieving complete response (CR) continue therapy for 2
courses after documentation of confirmed CR. Patients achieving partial response (PR)
continue therapy until progression or for 2 courses after documentation of stable PR.
Patients with stable disease continue therapy for a maximum of 6 courses. Cohorts of 3-6
patients receive escalating doses of lurtotecan liposome until the maximum tolerated dose
(MTD) is reached. The MTD is defined as the dose at which at least 2 of 6 patients
experience dose-limiting toxicity. Once the MTD is determined, up to 10 patients with
previously untreated solid tumors are treated at the recommended phase II dose (1 dose below
the MTD). Patients are followed at 4 weeks and then every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 20-25 patients will be accrued for this study within 12-15
Primary Purpose: Treatment
Hal W. Hirte, MD, FRCP(C)
Margaret and Charles Juravinski Cancer Centre
United States: Federal Government