NCT00415181

Pharmacogenomics of Paclitaxel in Ovarian Cancer

The Pharmacogenomics of Paclitaxel in Patients With Ovarian Cancer: Predictors of Toxicity and Response

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 93 (actual)
• Sponsor: University of Southern Denmark · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will try to determine whether or not certain genes are responsible for the huge variation in toxicity and effect observed between patients treated with paclitaxel (chemotherapeutic drug). Specifically we will study this in patients with ovarian cancer who receive paclitaxel/carboplatin chemotherapy after primary surgery.

Detailed description

Paclitaxel is an antineoplastic drug used in the treatment of ovarian cancer. The effect and toxicity is unpredictable in the individual patient. Paclitaxel is removed (eliminated) from the organism by oxidation. CYP2C8 is the enzyme mainly responsible. P-glycoprotein (Pgp) is an efflux transport protein natural to the human organism. Pgp is responsible for excretion of drugs via the bile and the kidneys and is thought to play a role in chemotherapy resistance. Paclitaxel is substrate for Pgp. Single nucleotide polymorphisms are possible causes for variation in both CYP2C8 and Pgp expression/function. We will study a possible role of these genetic variations as predictors of paclitaxel toxicity and effect and the possible implications for individual dosing in the future. We want to determine the metabolic capacity of approximately 100 ovarian cancer patients and comparing this with genotypes, acute toxicity(eg. bone marrow suppression and neuropathy) and response to treatment(ie. CA125 response, progression free survival and overall survival). The metabolic capacity is estimated using a "sparse sampling" approach applying advanced computerized pharmacokinetic/dynamic modelling as opposed to traditional "frequent sampling" pharmacokinetic studies which burden the individual patient more. Patients are recruited in collaboration with Oncological departments throughout Scandinavia.

Conditions

• Ovarian Neoplasms
• Fallopian Tube Neoplasms

Timeline

• Start date: 2006-09-01
• Primary completion: 2009-01-01
• Completion: 2013-03-01
• First posted: 2006-12-22
• Last updated: 2015-01-13

Locations

4 sites across 2 countries: Denmark, Sweden