The Effect of Docetaxel or Gemcitabine-based Chemotherapy in East Asian and Caucasian Patients
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00695994|
Recruitment Status : Completed
First Posted : June 12, 2008
Last Update Posted : November 1, 2012
The aims of this study are:
- to compare the toxicity profile and efficacy of gemcitabine/carboplatin or docetaxel in East Asian and Caucasian patients.
- to determine the genotype distribution of genes involved in docetaxel and gemcitabine pathways in East Asian and Caucasian patients.
to evaluate the association between genotypes and
- treatment toxicity
- treatment efficacy
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer Breast Cancer||Drug: Docetaxel Drug: gemcitabine and carboplatin||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||300 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Effect of Pharmacogenetics on Treatment Toxicities and Outcomes in East Asian and Caucasian Patients Undergoing Docetaxel or Gemcitabine-based Chemotherapy|
|Study Start Date :||October 2006|
|Actual Primary Completion Date :||September 2012|
|Actual Study Completion Date :||September 2012|
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 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.
Other Name: Docetaxel (Taxotere®, Sanofi-Aventis Inc.)
Experimental: Gemcitabine and carboplatin
Carboplatin will be administered as a 1-hour infusion on day 1 of a 21-day cycle. 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.
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.
- Treatment toxicities [ Time Frame: 36 weeks ]Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]
- objective tumour response, survival, median time to progression, and duration of response [ Time Frame: 36 weeks ]All patients included in the study must be assessed for response to treatment. Each patient will be assigned one of the following categories: 1) complete response, 2) partial response, 3) stable disease, 4) progressive disease, 5) early death from malignant disease, 6) early death from toxicity, 7) early death because of other cause, or 9) unknown (not assessable, insufficient data).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00695994
|National University Hospital|
|Principal Investigator:||Wei Peng Yong, MRCP, MB ChB||National University Hospital, Singapore|