Phase I Trial of Escalating Doses of BNP7787 in Patients With Solid Tumors Undergoing Treatment With Cisplatin and Taxol
- Determine the maximum tolerated dose (MTD) of dimesna administered prior to cisplatin
and paclitaxel in patients with solid tumors.
- Determine the dose related qualitative and quantitative side effects of dimesna
administered on this schedule in these patients.
- Determine the minimum safe volume of intravenous hydration after the determination of
the MTD of dimesna in these patients.
- Investigate the possible protective side effects of dimesna in reducing or preventing
the development of cisplatin induced nephrotoxicity and observe possible protective
effects against cisplatin or paclitaxel related neurotoxicity and myelosuppression in
- Investigate the pharmacokinetic behavior of dimesna in the plasma and urine on this
schedule of administration in this patient population.
OUTLINE: This is a dose-escalation, two-stage, multicenter study.
During stage I, patients receive a single dose of dimesna IV over 15 minutes 7 days prior to
chemotherapy. Patients then receive paclitaxel IV over 3 hours followed by dimesna IV over
15-30 minutes followed immediately by cisplatin IV over 1 hour on day 1 every 3 weeks.
Patients continue courses of paclitaxel, dimesna, and cisplatin every 3 weeks in the absence
of disease progression or unacceptable toxicity for up to 6 courses.
In stage I, cohorts of 3-6 patients each receive escalating doses of dimesna until the
maximum tolerated dose (MTD) is reached. The MTD is defined as the highest dose at which no
more than 1 of 6 patients experiences dose limiting toxicity (DLT). The MTD of dimesna is
then used in stage II of the study, in which the volume of pre and post cisplatin
intravenous saline hydration is reduced in cohorts of 3-6 patients each. The MTD intensity
of cisplatin is defined as the least saline hydration volume at which no more than 1 of 6
patients experience DLT.
PROJECTED ACCRUAL: Approximately 35 patients will be accrued into this study.
Patrick J. Creaven, MBBS, PhD
Roswell Park Cancer Institute
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|