Phase I trial to study the effectiveness of combining UCN-01 with cisplatin in treating patients who have advanced solid tumors. 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.
OBJECTIVES: I. To establish the maximum tolerated dose (MTD) of cisplatin in combination with UCN-01 in patients with advanced malignancies. II. To assess the toxicity and observe the potential antitumor activity of UCN-01 plus cisplatin in advanced malignancies at each dose level studies. III. To determine the pharmacokinetics of UCN-01 and cisplatin on this treatment schedule. IV. To perform laboratory correlative studies to investigate intermediate molecular markers of the activity of UCN-01 and cisplatin at the cellular level. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
MTD of cisplatin defined as the highest dose level in which six patients have been evaluated for toxicity with no more than one patient experiencing DLT attributable to the study drugs
Graded using the NCI CTCAE.
Time frame: 4 weeks
Toxicity observed at each dose level, graded using the NCI CTCAE
Summarized in terms of type, severity, time of onset, duration, and reversibility or outcome.
Time frame: Up to 7 years
Objective tumor response
Summarized at each dose level, and the number and percent responding combined across dose levels.
Time frame: Up to 7 years
Overall survival
Summarized with Kaplan-Meier plots.
Time frame: From registration to time of death due to any cause, assessed up to 7 years
Time to treatment failure
Summarized with Kaplan-Meier plots.
Time frame: From registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 7 years
Duration of response
Summarized with Kaplan-Meier plots.
Time frame: Up to 7 years
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