Clinical Trial: DNA Single Nucleotide Polymorphisms as Predictors of Toxicity

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Observational

Official Title: DNA Single Nucleotide Polymorphisms as Predictors of Platinum and Taxane Related Adverse Events in Ovarian, Fallopian Tube, and Peritoneal Cancer Patients

Brief Summary: The presence of single nucleotide polymorphisms (SNPs) in genes involved in platinum and taxane metabolism and detoxification have been correlated to increased risk of severe adverse events (AEs) when patients receive these drugs. The investigators propose studies to validate a comprehensive panel of twelve SNPs in ovarian cancer patients that may predict AEs when treated with therapies that include platinum and taxanes. Using these results to stratify patients to different dosing regimens, routes of administration, or in recurrent cancer to aid in drug selection, may improve outcome and reduce costs for the management of drug related side effects while not changing standard of care. Since these differences can be detected from blood, the determination of genotypes can be done using a standard blood sample taken after ovarian cancer is confirmed on the patient's pathology report. These genetic differences can be detected by QPCR and Next Generation Sequencing.

Detailed Summary:

The majority of ovarian cancer patients are treated with a combination of platinum- and taxane-based chemotherapy. While initial response rates are high (>90%), some patients experience severe AEs which can lead to discontinuation of therapy. However, both GOG and the paclitaxel package insert include treatment guidelines that involve a decreased dose regimen if AEs are encountered [1, 2]. The clinical validation of the genetic differences in these genes as biomarkers for severe AEs would allow the treating physician to alter dosing, thus increasing the time a patient could remain on the drug while decreasing side effects and unnecessary morbidity.

Another clinical utility of these genetic differences in ovarian cancer patient care is in the identification of which patients may not benefit from intraperitoneal (IP) chemotherapy or dose dense chemotherapy. While IP chemotherapy has been shown to improve patient outcome, the side effects are much more frequent and severe due to the high dose [3]. Testing the patients prior to treatment for predictive genotypes may factor into a doctor's decision to forego IP chemotherapy in favor of standard intravenous delivery. Dose dense chemotherapy has demonstrated improvements in outcome but also some increases in side effects [4, 5]. In both therapy regimens, the ability to stratify patients based on the risks of toxicities associated with treatment may lead to a greater benefit of IP or dose dense therapy while minimizing side effects and associated health care costs.

Previous studies in ovarian cancer have demonstrated that expression of the proteins ERCC1, GST, and p53 can affect the response to platinum based therapies in ovarian cancer patients [6-13]. When SNPs in the genes that encode these proteins were evaluated, a correlation to AEs in response to platinum-based therapies
Sponsor: OvaGene Oncology, Inc.

Current Primary Outcome: Occurrence of chemotherapy related toxicities including Anemia, Nephrotoxicity, Neutropenia, Neuropathy, and Thrombocytopenia associated with genotype. [ Time Frame: one year ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: OvaGene Oncology, Inc.

Dates:
Date Received: June 16, 2015
Date Started: July 2015
Date Completion: December 2017
Last Updated: June 18, 2015
Last Verified: June 2015