S0716 Vandetanib and Docetaxel in Treating Patients With Advanced Solid Tumors
RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vandetanib together with docetaxel may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vandetanib given together with docetaxel in treating patients with advanced solid tumors.
Head and Neck Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Genetic: proteomic profiling
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Pharmacokinetics and Pharmacodynamics of ZD6474 in Combination With Docetaxel in Advanced Solid Tumors|
- Pharmacodynamic parameters (percent inhibition of pERK, pKDR, and pEGFR) [ Designated as safety issue: No ]
- Correlation of pharmacokinetic profile with pharmacodynamic data and treatment-related toxicities [ Designated as safety issue: Yes ]
- Association between scientific correlates (microvessel density, cell death, circulating endothelial cells, ERK and pERK, and serum proteomics) and treatment outcomes and other patient characteristics [ Designated as safety issue: No ]
- Objective tumor response and clinically stable disease in patients with measurable disease at baseline [ Designated as safety issue: No ]
|Study Start Date:||September 2008|
|Estimated Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
- To investigate the differential biological effects in tumor tissues through pharmacodynamic endpoints (percent inhibition of pERK, pKDR, and pEGFR) and their correlation with pharmacokinetics of vandetanib in combination with docetaxel in patients with advanced solid tumors.
- To correlate the pharmacodynamic endpoints with the pharmacokinetics of this combination regimen in these patients.
- To recommend an optimal biological dose of this combination regimen for further testing.
- To correlate the pharmacokinetics with safety profiles of two dose levels of vandetanib when given in combination with docetaxel.
- To investigate scientific correlates, including serum proteomics and microvessel density (CD31) and cell death (TUNEL) using tumor tissue biopsy samples taken at baseline and during treatment.
- To determine the objective response in patients with measurable disease at baseline.
OUTLINE: This is a multicenter study.
Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After 6 weeks of treatment, patients who experience clinical benefit but poor tolerance to docetaxel may continue treatment with vandetanib alone.
Plasma samples are collected periodically for pharmacokinetic analysis, measurement of vandetanib trough levels, serum biomarker analysis, and serum proteomics. Tumor tissue samples are collected at baseline and once between days 36-38 for pharmacodynamic analysis.
After completion of study treatment, patients are followed up for up to 28 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00937417
|Study Chair:||Monica Mita, MD||Cancer Therapy and Research Center, Texas|