NCT00695994

The Effect of Docetaxel or Gemcitabine-based Chemotherapy in East Asian and Caucasian Patients

The Effect of Pharmacogenetics on Treatment Toxicities and Outcomes in East Asian and Caucasian Patients Undergoing Docetaxel or Gemcitabine-based Chemotherapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 300 (actual)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aims of this study are: 1. to compare the toxicity profile and efficacy of gemcitabine/carboplatin or docetaxel in East Asian and Caucasian patients. 2. to determine the genotype distribution of genes involved in docetaxel and gemcitabine pathways in East Asian and Caucasian patients. 3. to evaluate the association between genotypes and 1. treatment toxicity 2. treatment efficacy 3. pharmacokinetics.

Detailed description

Germline polymorphisms are inherited genetic variations present in all cells of the body. Mounting evidence has shown that genetic polymorphisms in drug metabolizing, transporter and targets genes are major determinants of response to drugs. The aims of this study are to compare (i) the toxicity profile and efficacy of gemcitabine/carboplatin or docetaxel, (ii) the distribution of genes involved in docetaxel and gemcitabine pathways and (iii) to evaluate the association between pharmacogenetics, pharmacokinetics and pharmacodynamics in East Asian and Caucasian patients. To date, most pharmacogenetic strategies are predominantly focused on the role of single genes, in the regulation of drug metabolism. However, there is clear evidence that treatment outcomes are under the control of a network of genes, each contributing to the patient's phenotype. In this study, we propose taking a global approach to include relevant candidate genes in drug pathways to evaluate the effect of polymorphisms and treatment outcomes. We have selected two commonly used chemotherapy regimens based on our previous observation of interethnic variability in treatment outcomes and candidate polymorphisms. By incorporating pharmacokinetic (drug level, drug elimination etc), pharmacodynamic (treatment response, survival etc) and pharmacogenetic approaches in clinical trials, it would enhance our understanding of the inter-individual variability in response and toxicity to drug treatment, and is the first step towards individualized drug treatment.

Conditions

• Non Small Cell Lung Cancer
• Breast Cancer

Interventions

Type	Name	Description
DRUG	Docetaxel	Docetaxel will be administered at a dose of 75 mg/m2 given as a 1-hour intravenous infusion on day 1 of a 21-day cycle. Docetaxel is re-constituted in 500 mL of normal saline and infused through a peripheral or central venous line. Docetaxel (Taxotere®, Sanofi-Aventis Inc.) is available in 80 mg and 20 mg in 2 mL polysorbate 80, 13% (w/w) ethanol in Water for Injection.
DRUG	gemcitabine and carboplatin	Gemcitabine (Gemzar®, Lily Inc.) is available in vials containing 1000 mg or 200 mg of active drug formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophilized powder. Carboplatin (Spectrum Pharmaceuticals, Inc.) is supplied as a 10 mg/mL aqueous solution. Unopened vials of gemcitabine are stable when stored at controlled room temperature at 25°C, protected from bright light. It can be diluted in normal saline or 5% dextrose. The solution remains stable for 8 hours at 25°C after reconstitution. Carboplatin will be administered as a 1-hour infusion on day 1 of a 21-day cycle. It will be given before gemcitabine at the dose to achieve an AUC of 5 using the Calvert formula. Gemcitabine will be administered as a 30-minute infusion at the dose of 1000 mg/m2 in 250 mL over 30 minutes, on day 1 and 8 of a 21-day cycle. It will be given after carboplatin infusion.

Timeline

• Start date: 2006-10-01
• Primary completion: 2012-09-01
• Completion: 2012-09-01
• First posted: 2008-06-12
• Last updated: 2012-11-01

Locations

1 site across 1 country: Singapore