A Phase I and Pharmacokinetic Study of Sequences of NSC 655649 (Rebeccamycin Analogue) and Cisplatin Without and With Granulocyte Colony-Stimulating Factor Support Every 21 Days
I. Determine the maximum tolerated doses of a rebeccamycin analogue and cisplatin with or
without filgrastim (G-CSF) in patients with advanced malignancies.
II. Determine the qualitative and quantitative toxicities of these regimens in these
III. Determine if the pharmacokinetics of a rebeccamycin analogue are affected by cisplatin
and if there are sequence dependent pharmacokinetic effects.
IV. Assess any antitumor effects of this regimen in these patients.
OUTLINE: This is a dose-escalation, multicenter study of a rebeccamycin analogue and
Part I (previously untreated or minimally pretreated patients): The first patient of each
cohort receives cisplatin IV over 1 hour followed 2 hours later by a rebeccamycin analogue
IV over 1 hour on day 1. The second patient in the same cohort receives the same drugs in
the reverse order. The drug sequence for each additional patient within the same cohort is
alternated with reference to the preceding patient. During each subsequent course, the study
drugs are administered to each patient in the reverse order as compared to the prior course.
Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or
Dose escalation is initially performed without filgrastim (G-CSF). Cohorts of 4-6 patients
receive escalating doses of a rebeccamycin analogue and cisplatin until the maximum
tolerated dose (MTD) of each drug is determined. The MTD is defined as the highest dose at
which less than 2 of 6 patients experience dose limiting toxicity (DLT). If 2 of the first 6
patients experience DLT, then dose escalation proceeds in combination with G-CSF treatment.
Patients receive G-CSF subcutaneously daily beginning on day 2 and continuing until blood
counts have recovered for 2 days or until approximately day 15. Cohorts of 4-6 patients
receive escalating doses of a rebeccamycin analogue and cisplatin as above. The MTD is
defined as above.
Part II (heavily pretreated patients): Heavily pretreated patients receive a rebeccamycin
analogue and cisplatin starting at 2 dose levels preceding the MTD from part I.
Patients are followed for at least 30 days.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Lisa Hammond, MD
University of Texas Health Science Center at San Antonio
United States: Food and Drug Administration
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|Cancer Therapy and Research Center||San Antonio, Texas 78229|
|St. Luke's Lutheran Hospital||San Antonio, Texas 78229|