Bortezomib and Gemcitabine in Treating Older Patients With Advanced Solid Tumors
RATIONALE: Bortezomib may stop the growth of solid tumors by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib and gemcitabine in treating older patients with advanced solid tumors.
Head and Neck Cancer
Drug: gemcitabine hydrochloride
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Bortezomib and Gemcitabine in Elderly Patients With Solid Tumors (X05227)|
- Maximum tolerated dose of bortezomib and gemcitabine [ Time Frame: Day 21 (Week 3 - Cycle 1) ] [ Designated as safety issue: Yes ]A minimum of a 3 week period (1 cycle) must be completed by all patients within a dose level before dose escalation to the next level may occur. A cycle is defined as treatment day 1 and 8 with follow-up through day 21.
- Toxicity [ Time Frame: 30 Days after Last Treatment ] [ Designated as safety issue: Yes ]Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 3.0)
- Disease response as measured by RECIST criteria [ Time Frame: Week 4 ] [ Designated as safety issue: No ]The best overall response is the best response recorded from the start of treatment until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since the treatment began.
- Characterization of gemcitabine and metabolite pharmacokinetics (as part of co-enrollment in Population Pharmacokinetics and Pharmacogenetics of Gemcitabine in Adult Patients with Solid Tumors") [ Time Frame: Pre-Dose ] [ Designated as safety issue: No ]Pharmacokinetics will be done in conjunction with the dosing day 1 of cycle 1 whenever possible.
|Study Start Date:||March 2007|
|Study Completion Date:||October 2009|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
Experimental: Gemcitabine / Bortezomib
Gemcitabine will be administered as a 30 minute intravenous infusion at the patient's assigned dose on day 1 and day 8 of a 21 day cycle.
Bortezomib will be given 1 hour after gemcitabine by IVP over 3 to 5 seconds followed by a standard saline on days 1 and 8 of a 21 day treatment cycle until disease progression or for a maximum of 6 cycles.
Bortezomib will be given 1 hour after gemcitabine by intravenous pyelogram (IVP) over 3 to 5 seconds followed by a standard saline flush or through a running intravenous (IV) line at the patient's assigned dose (1.0 up to 1.8 mg/m^2) on days 1 and 8 of a 21 day treatment cycle until disease progression or for a maximum of 6 cycles.
Other Name: VelcadeDrug: gemcitabine hydrochloride
Gemcitabine will be administered as a 30 minute intravenous infusion at the patient's assigned dose (800 up to 1000 mg/m^2) on day 1 and day 8 of a 21 day cycle.
Other Name: Gemzar
- To determine the maximum tolerated dose of weekly bortezomib and gemcitabine in treating elderly patients with advanced solid tumors.
- To characterize the quantitative and qualitative toxicities of bortezomib and gemcitabine in these patients.
- To obtain preliminary information about the anti-tumor activity of bortezomib and gemcitabine.
- To characterize gemcitabine and metabolite pharmacokinetics in patients receiving concurrent bortezomib therapy.
OUTLINE: This is a phase I dose escalation study of bortezomib and gemcitabine.
Patients receive gemcitabine intravenously (IV) over 30 minutes followed 1 hour later by bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of gemcitabine and bortezomib until the maximum tolerated dose of the combination is determined.
Blood is collected periodically for pharmacokinetic and pharmacogenetic studies.
After completion of study treatment, patients are followed every 3 months for up to 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00620295
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Arkadiusz Dudek, MD||Masonic Cancer Center, University of Minnesota|