Pharmacogenomics of Paclitaxel in Ovarian Cancer

Ovarian Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00415181
• Other study ID #: AKF-319pro
• Status: Completed
• Phase: N/A
• First received: December 21, 2006
• Last updated: January 12, 2015
• Start date: September 2006
• Est. completion date: March 2013

Study information

• Verified date: December 2006
• Source: University of Southern Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection Agency
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: March 2013
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Fallopian Tube Neoplasms
• Neoplasms
• Ovarian Neoplasms

Locations

Country	Name	City	State
Denmark	Department of oncology, Herlev Hospital	Herlev
Denmark	Department of Oncology, Odense University Hospital	Odense
Denmark	Department of Oncology, Vejle Hospital	Vejle
Sweden	Department of Oncology, University Hospital of Lund	Lund

Sponsors (3)

Lead Sponsor	Collaborator
University of Southern Denmark	Danish Clinical Intervention Research Academy, Ministry of the Interior and Health, Denmark

Countries where clinical trial is conducted

Denmark,  Sweden, 

References & Publications (1)

Bergmann TK, Brasch-Andersen C, Gréen H, Mirza M, Pedersen RS, Nielsen F, Skougaard K, Wihl J, Keldsen N, Damkier P, Friberg LE, Peterson C, Vach W, Karlsson MO, Brosen K. Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharma — View Citation