Alvocidib in Treating Patients With Locally Advanced or Metastatic Solid Tumors
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: alvocidib Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors|
- Adverse events of dose escalated alvocidib administered in patients with advanced solid tumors [ Time Frame: At weeks 1-4, 7-10, 11 or 12, and within 4 weeks after the completion of study treatment ]Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
- Pharmacokinetics of alvocidib administered in this schedule [ Time Frame: After the first dose of treatment drug ]The pharmacokinetic parameters include Cmax, Css, Clearance, t1/2 α, t1/2 β, central volume of distribution and steady state volume of distribution.
- Immunomodulatory effects of alvocidib [ Time Frame: Baseline, days 1 and 15 of courses 1 and 2, and within 4 weeks after the completion of study treatment ]Gene expression quantified using Real Time PCR; type 1 and type 2 cytokines, co-stimulatory molecules, and adhesion molecules in PBMCs. Activation of lymphocyte subsets and presence of co-stimulatory and adhesion molecules assessed using multicolor flow cytometry. IL-6 levels in plasma will be measured by ELISA. T-cells will be enriched from PBMCs using mAb-coated immunomagnetic beads and activated with anti-CD3/anti-CD28 mAbs, inomycin or PMA. Cytokine production will be measured using cytometric bead array.
- Pharmacogenomics studies on procured PBMCs if clinical responses are observed [ Time Frame: Baseline, and within 4 weeks after the completion of study treatment ]Performed if clinical responses are observed. Examine for selected polymorphisms of genes influencing alvocidib metabolism and/or resistance genes that may predict response or toxicity. These changes will be correlated with AUC, toxicity and clinical response to therapy.
- Measurement of serum tumor markers depending on the tumor type [ Time Frame: Baseline, week 11 or 12, and within 4 weeks after the completion of study treatment ]Markers include CEA, CA 19-9, CA 15-3, PSA, LDH, AFP, b-HCG, pancreastatin, gastrin, pancreatic polypeptide, glucagon, substance-P, neurotensin, calcitonin, somatostatin, vasoactive intestinal peptide, gastrin releasing polypeptide, ACTH, and chromogranin-A.
|Study Start Date:||February 2006|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy, biological therapy)
Patients receive alvocidib IV over 4½ hours once weekly in weeks 1-4. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. Determine the toxicity profile and dose-limiting toxicity of flavopiridol (alvocidib) in patients with locally advanced or metastatic solid tumors.
II. Determine the maximum tolerated dose of this drug in these patients.
I. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
II. Determine the immunomodulatory effects of this drug in these patients. III. Determine pharmacogenomics of this drug, using peripheral blood mononuclear cells, in patients who experience clinical response.
OUTLINE: This is a pilot, dose-escalation study.
Patients receive alvocidib intravenously (IV) over 4½ hours once weekly in weeks 1-4. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease after 4 courses of therapy discontinue study treatment. Patients who achieve complete remission (CR) receive 1 additional course of therapy beyond documentation of CR. Cohorts of 3-6 patients receive escalating doses of alvocidib 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. A total of 10 patients are treated at the MTD.
After completion of study treatment, patients are followed within 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112684
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Manisha Shah||Ohio State University|