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Principal Investigator has left Inova
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The purpose of this research is to see if adjusting the dose of 5-fluorouracil based on its concentration in your blood will improve the treatment of your metastatic colon cancer.
5-fluorouracil (5-FU) has been the most widely used agent in the treatment of early stage and advanced colorectal cancer. Traditionally, 5-FU dosing is based on body surface area (BSA). However, BSA-dosing has been associated with a wide range of pharmacokinetic (PK) variability, resulting in marked differences in drug exposure and toxicities in an individual. There is a significant association between the risk of 5-FU-related toxicities and the extent of 5- FU systemic exposure, which can be measured using a well-established pharmacokinetic (PK) assay.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chemotherapy with 5-FU/Leucovorin (LV) alone, with oxaliplatin or irinotecan or both | Experimental | Plasma specimens will be collected for the measurement of plasma 5-FU level from patients receiving 5-FU/LV alone, with oxaliplatin (mFOLFOX6) or irinotecan (FOLFIRI), or both (mFOLFOXIRI) chemotherapy. 5-FU doses will be modified based on the assay results. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biweekly 5-FLUOROURACIL (5-FU) | Drug | 5-FU 2400 mg/m². Infusion for 46 hours. Leucovorin 200 mg/m². Either a vascular endothelial growth factor (VEGF) inhibitor or epidermal growth factor (EGFR) inhibitor or may be added to the regimen at the discretion of the treating physician. Repeat every 2 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility Of Pharmacokinetically (PK) Guided Does Adjustment of 5-Fluorouracil (5-FU) In a Community Oncology Setting | The Feasibility Of Pharmacokinetically Guided Does Adjustment of 5-Fluorouracil In a Community Oncology Setting is Defined as 80% Success Rate among Patients Who Has Completed Four Sequential PK blood Draws with Subsequent Dose Adjustments During the Treatment with 5-FU based Drug Therapy. | From enrollment to the end of treatment at 8 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jasmine Huynh, MD | Inova Schar Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Inova Health Care Service | Falls Church | Virginia | 22042 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14657227 | Background | Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004 Jan 15;22(2):229-37. doi: 10.1200/JCO.2004.05.113. Epub 2003 Dec 2. | |
| 32164906 |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D005472 | Fluorouracil |
| D002955 | Leucovorin |
| D000077146 | Irinotecan |
| D000077150 | Oxaliplatin |
| ID | Term |
|---|---|
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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Each cycle of chemotherapy is 2 weeks long, so you will be receiving treatment on the study for a total of 8 weeks. You will also need additional imaging (CT scans) after you complete the first four cycles of chemotherapy, which brings your total time in the study to about 3 months including treatment and follow-up.
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|
|
| Biweekly Modified FOLFOX6 | Drug | Oxaliplatin 85 mg/m². 5-FU 400 mg/m² on day 1 as bolus (OPTIONAL). 5-FU 2400 mg/m² Infusion for 46 hours. Leucovorin 200 mg/m2. Repeat every 2 weeks |
|
|
| Biweekly FOLFIRI | Drug | Irinotecan 180 mg/m2. 5-FU 400 mg/m2 on day 1 as bolus (OPTIONAL). 5-FU 2400 mg/m2 Infusion for 46 hours. Leucovorin 200 mg/m2. Repeat every 2 weeks. |
|
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| mFOLFOXIRI | Drug | Irinotecan 165 mg/m2. Oxaliplatin 85 mg/m2. 5-FU 2400 mg/m2 Infusion for 46 hours. Repeat every 2 weeks. |
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| Cremolini C, Antoniotti C, Rossini D, Lonardi S, Loupakis F, Pietrantonio F, Bordonaro R, Latiano TP, Tamburini E, Santini D, Passardi A, Marmorino F, Grande R, Aprile G, Zaniboni A, Murgioni S, Granetto C, Buonadonna A, Moretto R, Corallo S, Cordio S, Antonuzzo L, Tomasello G, Masi G, Ronzoni M, Di Donato S, Carlomagno C, Clavarezza M, Ritorto G, Mambrini A, Roselli M, Cupini S, Mammoliti S, Fenocchio E, Corgna E, Zagonel V, Fontanini G, Ugolini C, Boni L, Falcone A; GONO Foundation Investigators. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020 Apr;21(4):497-507. doi: 10.1016/S1470-2045(19)30862-9. Epub 2020 Mar 9. |
| 27229175 | Background | Fang L, Xin W, Ding H, Zhang Y, Zhong L, Luo H, Li J, Yang Y, Huang P. Pharmacokinetically guided algorithm of 5-fluorouracil dosing, a reliable strategy of precision chemotherapy for solid tumors: a meta-analysis. Sci Rep. 2016 May 27;6:25913. doi: 10.1038/srep25913. |
| 15689586 | Background | Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005 Feb 3;352(5):476-87. doi: 10.1056/NEJMra040958. No abstract available. |
| 18445839 | Background | Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M. Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol. 2008 May 1;26(13):2099-105. doi: 10.1200/JCO.2007.13.3934. |
| 28248415 | Background | Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, Jemal A. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017 May 6;67(3):177-193. doi: 10.3322/caac.21395. Epub 2017 Mar 1. |
| 23177514 | Background | Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/S0140-6736(12)61900-X. Epub 2012 Nov 22. |
| 22382460 | Background | Kaldate RR, Haregewoin A, Grier CE, Hamilton SA, McLeod HL. Modeling the 5-fluorouracil area under the curve versus dose relationship to develop a pharmacokinetic dosing algorithm for colorectal cancer patients receiving FOLFOX6. Oncologist. 2012;17(3):296-302. doi: 10.1634/theoncologist.2011-0357. Epub 2012 Mar 1. |
| 8630950 | Background | Gamelin EC, Danquechin-Dorval EM, Dumesnil YF, Maillart PJ, Goudier MJ, Burtin PC, Delva RG, Lortholary AH, Gesta PH, Larra FG. Relationship between 5-fluorouracil (5-FU) dose intensity and therapeutic response in patients with advanced colorectal cancer receiving infusional therapy containing 5-FU. Cancer. 1996 Feb 1;77(3):441-51. doi: 10.1002/(SICI)1097-0142(19960201)77:33.0.CO;2-N. |
| 19935361 | Background | Beumer JH, Boisdron-Celle M, Clarke W, Courtney JB, Egorin MJ, Gamelin E, Harney RL, Hammett-Stabler C, Lepp S, Li Y, Lundell GD, McMillin G, Milano G, Salamone SJ. Multicenter evaluation of a novel nanoparticle immunoassay for 5-fluorouracil on the Olympus AU400 analyzer. Ther Drug Monit. 2009 Dec;31(6):688-94. doi: 10.1519/JSC.0b013e3181b866d0. |
| 10561167 | Background | Gamelin E, Boisdron-Celle M, Guerin-Meyer V, Delva R, Lortholary A, Genevieve F, Larra F, Ifrah N, Robert J. Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer: A potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. J Clin Oncol. 1999 Apr;17(4):1105. doi: 10.1200/JCO.1999.17.4.1105. |
| 29545919 | Background | Morawska K, Goirand F, Marceau L, Devaux M, Cueff A, Bertaut A, Vincent J, Bengrine-Lefevre L, Ghiringhelli F, Schmitt A. 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer. Oncotarget. 2018 Jan 30;9(14):11559-11571. doi: 10.18632/oncotarget.24338. eCollection 2018 Feb 20. |
| 27256667 | Background | Wilhelm M, Mueller L, Miller MC, Link K, Holdenrieder S, Bertsch T, Kunzmann V, Stoetzer OJ, Suttmann I, Braess J, Birkmann J, Roessler M, Moritz B, Kraff S, Salamone SJ, Jaehde U. Prospective, Multicenter Study of 5-Fluorouracil Therapeutic Drug Monitoring in Metastatic Colorectal Cancer Treated in Routine Clinical Practice. Clin Colorectal Cancer. 2016 Dec;15(4):381-388. doi: 10.1016/j.clcc.2016.04.001. Epub 2016 May 7. |
| 7349890 | Background | Kirkwood JM, Ensminger W, Rosowsky A, Papathanasopoulos N, Frei E 3rd. Comparison of pharmacokinetics of 5-fluorouracil and 5-fluorouracil with concurrent thymidine infusions in a Phase I trial. Cancer Res. 1980 Jan;40(1):107-13. |
| 6211226 | Background | Au JL, Rustum YM, Ledesma EJ, Mittelman A, Creaven PJ. Clinical pharmacological studies of concurrent infusion of 5-fluorouracil and thymidine in treatment of colorectal carcinomas. Cancer Res. 1982 Jul;42(7):2930-7. |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006571 |
| Heterocyclic Compounds |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |