DNA Single Nucleotide Polymorphisms as Predictors of Toxicity

NCT02478476 | Unknown DMC

• 1 other identifier: IRBNet#673096
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Occurrence of chemotherapy related toxicities including Anemia, Nephrotoxicity, Neutropenia, Neuropathy, and Thrombocytopenia associated with genotype.

  Specific genotypes will be evaluated as predictors of toxicity when patients receive platinum and/or taxane based chemotherapy.

  one year

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with pathologically confirmed ovarian, fallopian tube, or peritoneal cancer scheduled to receive platinum and/or taxane based chemotherapy.

You may qualify if:

• Female, greater than or equal to 18 years of age.
• Must have pathologically confirmed ovarian, fallopian tube, or primary peritoneal cancer.
• Able to provide a blood sample (3-5ml).
• Planned course of therapy includes a platinum and/or taxane based chemotherapy.

You may not qualify if:

• Has a clinically significant (per judgment of the PI) neurodegenerative, hematological, or cardiac related disease.
• Has received prior chemotherapy.
• Unable or unwilling to provide informed consent.

Sponsors & Collaborators

• OvaGene Oncology, Inc.: lead

Study Sites (1)

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

Related Publications (22)

• Paclitaxel, [package insert], Bristol-Meyers Squibb Company, Princeton, NJ, April 2011.

  BACKGROUND

• Chemotherapy procedure Manual, Gynecologic Oncology Group, January 2004.

  BACKGROUND

• Wenzel LB, Huang HQ, Armstrong DK, Walker JL, Cella D; Gynecologic Oncology Group. Health-related quality of life during and after intraperitoneal versus intravenous chemotherapy for optimally debulked ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Feb 1;25(4):437-43. doi: 10.1200/JCO.2006.07.3494.

  PMID: 17264340 BACKGROUND

• Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, Ochiai K, Noda K; Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. doi: 10.1016/S0140-6736(09)61157-0. Epub 2009 Sep 18.

  PMID: 19767092 BACKGROUND

• Glaze S, Teitelbaum L, Chu P, Ghatage P, Nation J, Nelson G. Dose-dense paclitaxel with carboplatin for advanced ovarian cancer: a feasible treatment alternative. J Obstet Gynaecol Can. 2013 Jan;35(1):61-7. doi: 10.1016/s1701-2163(15)31050-1.

  PMID: 23343799 BACKGROUND

• Milovic-Kovacevic M, Srdic-Rajic T, Radulovic S, Bjelogrlic S, Gavrilovic D. Expression of ERCC1 protein in biopsy specimen predicts survival in advanced ovarian cancer patients treated with platinum-based chemotherapy. J BUON. 2011 Oct-Dec;16(4):708-14.

  PMID: 22331726 BACKGROUND

• Scheil-Bertram S, Tylus-Schaaf P, du Bois A, Harter P, Oppitz M, Ewald-Riegler N, Fisseler-Eckhoff A. Excision repair cross-complementation group 1 protein overexpression as a predictor of poor survival for high-grade serous ovarian adenocarcinoma. Gynecol Oncol. 2010 Nov;119(2):325-31. doi: 10.1016/j.ygyno.2010.07.018. Epub 2010 Aug 21.

  PMID: 20728204 BACKGROUND

• Steffensen KD, Waldstrom M, Jakobsen A. The relationship of platinum resistance and ERCC1 protein expression in epithelial ovarian cancer. Int J Gynecol Cancer. 2009 Jul;19(5):820-5. doi: 10.1111/IGC.0b013e3181a12e09.

  PMID: 19574766 BACKGROUND

• Steffensen KD, Waldstrom M, Jeppesen U, Brandslund I, Jakobsen A. Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer. Int J Gynecol Cancer. 2008 Jul-Aug;18(4):702-10. doi: 10.1111/j.1525-1438.2007.01068.x. Epub 2007 Oct 24.

  PMID: 17961161 BACKGROUND

• Hirazono K, Shinozuka T, Kuroshima Y, Itoh H, Kawai K. Immunohistochemical expression of glutathione S-transferase pi (GST-pi) and chemotherapy response in malignant ovarian tumors. J Obstet Gynaecol (Tokyo 1995). 1995 Jun;21(3):305-12. doi: 10.1111/j.1447-0756.1995.tb01015.x.

  PMID: 8590371 BACKGROUND

• Howells RE, Dhar KK, Hoban PR, Jones PW, Fryer AA, Redman CW, Strange RC. Association between glutathione-S-transferase GSTP1 genotypes, GSTP1 over-expression, and outcome in epithelial ovarian cancer. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):242-50. doi: 10.1111/j.1048-891X.2004.014207.x.

  PMID: 15086723 BACKGROUND

• Bali A, O'Brien PM, Edwards LS, Sutherland RL, Hacker NF, Henshall SM. Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clin Cancer Res. 2004 Aug 1;10(15):5168-77. doi: 10.1158/1078-0432.CCR-03-0751.

  PMID: 15297421 BACKGROUND

• Ferrandina G, Fagotti A, Salerno MG, Natali PG, Mottolese M, Maneschi F, De Pasqua A, Benedetti-Panici P, Mancuso S, Scambia G. p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer. Br J Cancer. 1999 Oct;81(4):733-40. doi: 10.1038/sj.bjc.6690756.

  PMID: 10574264 BACKGROUND

• Khrunin AV, Moisseev A, Gorbunova V, Limborska S. Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients. Pharmacogenomics J. 2010 Feb;10(1):54-61. doi: 10.1038/tpj.2009.45. Epub 2009 Sep 29.

  PMID: 19786980 BACKGROUND

• Sakano S, Hinoda Y, Sasaki M, Wada T, Matsumoto H, Eguchi S, Shinohara A, Kawai Y, Hara T, Nagao K, Hara T, Naito K, Matsuyama H. Nucleotide excision repair gene polymorphisms may predict acute toxicity in patients treated with chemoradiotherapy for bladder cancer. Pharmacogenomics. 2010 Oct;11(10):1377-87. doi: 10.2217/pgs.10.106.

  PMID: 21047201 BACKGROUND

• McWhinney-Glass S, Winham SJ, Hertz DL, Yen Revollo J, Paul J, He Y, Brown R, Motsinger-Reif AA, McLeod HL; Scottish Gynaecological Clinical Trials Group. Cumulative genetic risk predicts platinum/taxane-induced neurotoxicity. Clin Cancer Res. 2013 Oct 15;19(20):5769-76. doi: 10.1158/1078-0432.CCR-13-0774. Epub 2013 Aug 20.

  PMID: 23963862 BACKGROUND

• Hertz DL, Motsinger-Reif AA, Drobish A, Winham SJ, McLeod HL, Carey LA, Dees EC. CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel. Breast Cancer Res Treat. 2012 Jul;134(1):401-10. doi: 10.1007/s10549-012-2054-0. Epub 2012 Apr 18.

  PMID: 22527101 BACKGROUND

• Hertz DL, Roy S, Motsinger-Reif AA, Drobish A, Clark LS, McLeod HL, Carey LA, Dees EC. CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel. Ann Oncol. 2013 Jun;24(6):1472-8. doi: 10.1093/annonc/mdt018. Epub 2013 Feb 14.

  PMID: 23413280 BACKGROUND

• Corthals SL, Kuiper R, Johnson DC, Sonneveld P, Hajek R, van der Holt B, Magrangeas F, Goldschmidt H, Morgan GJ, Avet-Loiseau H. Genetic factors underlying the risk of bortezomib induced peripheral neuropathy in multiple myeloma patients. Haematologica. 2011 Nov;96(11):1728-32. doi: 10.3324/haematol.2011.041434. Epub 2011 Jul 26.

  PMID: 21791469 BACKGROUND

• Velasco R, Petit J, Clapes V, Verdu E, Navarro X, Bruna J. Neurological monitoring reduces the incidence of bortezomib-induced peripheral neuropathy in multiple myeloma patients. J Peripher Nerv Syst. 2010 Mar;15(1):17-25. doi: 10.1111/j.1529-8027.2010.00248.x.

  PMID: 20433602 BACKGROUND

• Pike CT, Birnbaum HG, Muehlenbein CE, Pohl GM, Natale RB. Healthcare costs and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer. Chemother Res Pract. 2012;2012:913848. doi: 10.1155/2012/913848. Epub 2012 Mar 14.

  PMID: 22482054 BACKGROUND

• Calhoun EA, Welshman EE, Chang CH, Lurain JR, Fishman DA, Hunt TL, Cella D. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer. 2003 Nov-Dec;13(6):741-8. doi: 10.1111/j.1525-1438.2003.13603.x.

  PMID: 14675309 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Study Officials

• William Ricketts, PhD

  OvaGene Oncology

  STUDY DIRECTOR

Central Study Contacts

Robert W Holloway, MD

CONTACT

(407)303-2422

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 23, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2017
• Last Updated: June 23, 2015

Record last verified: 2015-06

Locations

US (1)