UCN-01 and Cisplatin in Treating Patients With Advanced Solid Tumors
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth and may help cisplatin kill more cancer cells by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the effectiveness of combining UCN-01 with cisplatin in treating patients who have advanced solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Dose Escalation Study Of UCN-01 (NSC 638850) Plus Cisplatin In Advanced Malignant Solid Tumors|
- Maximum tolerated dose (MTD). [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]To establish the maximum tolerated dose (MTD) of cisplatin in combination with UCN-01 in patients with advanced malignancies.
- Pharmacokinetics [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]To determine the pharmacokinetics of UCN-01 and cisplatin.
- Toxicity assessment. [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]To assess the toxicity of UCN-01 plus cisplatin in advanced malignancies at each dose level studied.
- Preliminary efficacy observation [ Time Frame: Cycle 1-2 (to day 56) ] [ Designated as safety issue: No ]To observe the potential antitumor activity of UCN-01 plus cisplatin in advanced malignancies at each dose level studied.
- Molecular correlative studies. [ Time Frame: Cycles 1-2 (up to day 56) ] [ Designated as safety issue: No ]To perform laboratory correlative studies to investigate intermediate molecular markers of the activity of UCN-01 and cisplatin at the cellular level (geminin immunohistochemistry, AKT Thr 308 phosphorylation), and determinants of UCN-01 pharmacokinetics (salivary and plasma alpha-1-acid-glycoprotein (AAG)).
|Study Start Date:||March 2001|
|Study Completion Date:||January 2007|
|Primary Completion Date:||January 2007 (Final data collection date for primary outcome measure)|
- NSC 638850
- cis-diamminedichloridoplatinum(II) (CDDP)
- CAS 15663-27-1
- NSC 119875
- Determine the maximum tolerated dose of cisplatin when administered with UCN-01 in patients with advanced solid tumors.
- Determine the toxicity and potential antitumor activity of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is a dose-escalation study of cisplatin.
Patients receive cisplatin IV over 1 hour on day 1 and UCN-01 IV continuously over 36-72 hours on day 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of cisplatin 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.
Patients are followed every 2-3 months for at least 1 year.
PROJECTED ACCRUAL: A total of 9-30 patients will be accrued for this study within 12-18 months.
|United States, New Hampshire|
|Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756-0002|
|Study Chair:||Raymond P. Perez, MD||Norris Cotton Cancer Center|