Bortezomib, Fluorouracil, and Leucovorin Calcium in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: bortezomib Drug: fluorouracil Drug: leucovorin calcium Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Study of PS-341 in Combination With 5-FU/LV in Solid Tumors|
- MTD, defined as the highest dose tested in which none or only one patient experienced DLT attributable to the study drug(s), when at least 6 patients were treated at that dose and are evaluable for toxicity, graded according to the NCI CTC version 2.0 [ Time Frame: Up to 21 days ]
- Incidence of adverse events, graded according to NCI CTC version 2.0 [ Time Frame: Up to 7 years ]The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and course.
- Survival [ Time Frame: Up to 7 years ]Will be summarized with Kaplan-Meier plots.
- Time to failure [ Time Frame: Up to 7 years ]Will be summarized with Kaplan-Meier plots.
|Study Start Date:||September 2000|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
Experimental: Treatment (bortezomib, fluorouracil, leucovorin calcium)
Patients receive bortezomib IV on days 1 and 4 and fluorouracil IV and leucovorin calcium IV on day 1 weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: fluorouracil
Other Names:Drug: leucovorin calcium
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of PS-341 (bortezomib) when administered as a bolus injection two times a week (on days 1 and 4) for 2 weeks followed by one week of rest.
II. To evaluate the pharmacodynamics of PS-341 by determining the 20S proteasome and nuclear factor kappa-light chain enhancer of activated B cells (NFkB) inhibition in blood of patients treated with intravenous PS-341 combined with weekly fluorouracil (5-FU) and leucovorin calcium (LV).
I. To identify any objective tumor response in patients treated with intravenous PS-341.
II. To evaluate the relationship between inhibition of the 20S proteasome and NFkB and clinical toxicity.
III. To obtain preliminary data on molecular correlates of response to PS-341 and 5-FU and LV including genes involved in apoptosis, cell cycle control, transcriptional regulation and adhesion/angiogenesis based on the mechanisms of PS-341 IV. To examine the pharmacokinetics of 5-FU when co-administered with PS-341.
OUTLINE: This is a dose-escalation study of bortezomib.
Patients receive bortezomib intravenously (IV) on days 1 and 4 and fluorouracil IV and leucovorin calcium IV on day 1 weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00007878
|United States, California|
|University of Southern California|
|Los Angeles, California, United States, 90033-0804|
|Principal Investigator:||Heinz-Josef Lenz||University of Southern California|