The Pharmacogenomics of Paclitaxel in Patients With Ovarian Cancer: Predictors of Toxicity and Response
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 93
- 试验地点
- 4
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnose and histology of invasive epithelial ovarian/tuba or peritoneal cancer
- •FIGO stage IIb-IV any grade or FIGO Ia-IIa only grade 3 or clear cell carcinoma (any stage and grade)
- •Natural candidate for paclitaxel 175mg/m2 + Carboplatin (AUC=5-6)
- •Baseline CA125≥70 AND/OR evaluable disease after RECIST (incl ultrasound)
- •18 years or older
- •Caucasian (ie.parents and grandparents are Caucasian)
- •Performance status 2 or lower (after WHO/ECOG)
排除标准
- •Prior malignant disease apart from cervical carcinoma in situ and basal cell carcinoma of the skin
- •Prior chemo / radiotherapy
- •Ongoing or imminent other chemotherapies
- •Pregnant or lactating
- •Fertile woman of childbearing potential not willing to use adequate contraception
- •Neurological symptoms (any kind) worse than CTCAE grade 1
- •Active infection or other serious disease that could impair on treatment and/or follow-up